Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Depression & Other Neuropsychiatric Symptoms After Traumatic Brain Injury (TBI) (rTMS TBI)

• ClinicalTrials.gov Identifier: NCT02367521
• Recruitment Status: Completed
• First Posted: February 20, 2015
• Results First Posted: August 31, 2018
• Last Update Posted: August 31, 2018
• Sponsor: Johns Hopkins University
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): Johns Hopkins University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: TBI Depression
• Interventions: Combination Product: Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS); Device: Sham Comparator: Sham Treatment
• Enrollment: 70

Participant Flow

Recruitment Details	70 participants passed screening & were enrolled in study. 36 were not randomized.14 lost to follow-up, 5 refused due to scheduling, 5 did not meet DSM IV criteria: major depression, 3 concerns about receiving rTMS, 2 psychotropics, 2 did not have TBI, 1 using illicit drugs, 1 skull fracture, 1 severe TBI, 1 with seizure history, 1 MRI focal lesion
Pre-assignment Details

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Period Title: Overall Study
Started	17	17
Completed	13	17
Not Completed	4	0
Reason Not Completed
severe headache after intervention	2	0
unable to find transportation	2	0

Baseline Characteristics

Arm/Group Title		Sham Treatment	LFR rTMS	Total
Arm/Group Description		Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Total of all reporting groups
Overall Number of Baseline Participants		17	13	30
Baseline Analysis Population Description		Baseline characteristics were only documented and analyzed for participants who complete the study. Details for the four who dropped out are no longer available.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	17 participants	13 participants	30 participants
		40.2 (14.6)	39.8 (14.2)	40 (14.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	17 participants	13 participants	30 participants
	Female	6 35.3%	8 61.5%	14 46.7%
	Male	11 64.7%	5 38.5%	16 53.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	17 participants	13 participants	30 participants
White		10 58.8%	9 69.2%	19 63.3%
Non-White		7 41.2%	4 30.8%	11 36.7%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	17 participants	13 participants	30 participants
		17 100.0%	13 100.0%	30 100.0%
Months Depressed Since Injury; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	17 participants	13 participants	30 participants
		39.4 (43)	39.6 (36.1)	39.47 (39.51)

Outcome Measures

1. Primary Outcome

Title	Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale
Description	The HAM-D was used to determine the effectiveness of LFR rTMS for the treatment of post-TBI depression. The scale ranges from 0-54, with 0-7 = Normal; 8-13= Mild Depression; 14-18= Moderate Depression, 19-22= Severe Depression, >/= 23 = Very Severe Depression.
Time Frame	Mean at baseline, 4 weeks, 8 weeks, 12 weeks, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	23.154 (4.375)	23.076 (4.356)
4 weeks	13.154 (8.444)	12.706 (6.697)
8 weeks	12.538 (9.744)	12.647 (6.901)
12 weeks	14.077 (10.21)	12.824 (8.435)
16 weeks	11.154 (9.529)	12.941 (8.877)

2. Primary Outcome

Title	Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S)
Description	The CGI scale is broken down into the CGI-S and CGI-I components. CGI-S is the baseline severity of mental illness. 1= normal, not at all ill; 2= borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The CGI-S is only performed at baseline. The CGI-I component (which is any measure after intervention) is as follows: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.
Time Frame	Mean at baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
CGI Baseline (severity)	4.846 (0.801)	5 (0.791)
CGI 4 weeks (improvement)	2.308 (1.109)	2.824 (1.334)
CGI 8 weeks (improvement)	2.385 (1.044)	2.471 (1.125)
CGI 12 weeks (improvement)	2.385 (1.0444)	2.588 (1.064)
CGI 16 weeks (improvement)	2.077 (0.854)	2.471 (1.281)

3. Primary Outcome

Title	Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI)
Description	The BSSI scale is used to assess the degree of suicidal ideation. The scale ranges from 0-38, with 0= no suicidality, and 38 = highest severity of suicidal ideation
Time Frame	Mean at baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	0.462 (1.127)	1.294 (1.896)
4 weeks	0.077 (0.277)	0.706 (1.359)
8 weeks	0.154 (0.376)	0.353 (0.862)
12 weeks	0 (0)	0.529 (1.007)
16 weeks	0.00 (0)	0.471 (0.943)

4. Secondary Outcome

Title	Ability to Inhibit Cognitive Interference as Assessed by the Stroop Color Word Test (SCWT)
Description	The SCWT is used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute. Participants are required to read three different tables as fast as possible. Two of the tables represent the "congruous condition" in which participants are required to read names of colors printed in black ink and name different color patches. In the third table, "incongruous condition" the color-words are printed in a different color in (ie: the word "red" is printed in green ink). Within this third table, participants are required to name the color of the ink instead of reading the word. The score is based on the number of items completed, which ranges from 0 to 100, with a higher score reflecting a better outcome.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: items completed
0 weeks	43.2 (13.3)	42.4 (8.2)
16 weeks	45.4 (11.9)	43.1 (11.6)

5. Secondary Outcome

Title	Cognitive Reasoning as Assessed by the Number of Completed Categories on the Wisconsin Card Scoring Test (WCST)
Description	The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of completed categories, ranging from 0-6. A higher score reflects a better outcome.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: completed categories
0 weeks	5.5 (0.707)	6 (0)
16 weeks	6 (0)	6 (0)

6. Secondary Outcome

Title	Cognitive Reasoning as Assessed by the Number of Errors Made on the Wisconsin Card Sorting Test (WCST)
Description	The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of errors, ranging from 0-128. A higher score reflects a poorer outcome.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: errors
Baseline	26 (24.042)	11 (5.354)
16 weeks	10.5 (2.881)	8.667 (1.633)

7. Secondary Outcome

Title	Cognitive Reasoning as Assessed by the Number of Correct Trials on the Wisconsin Card Scoring Test (WCST)
Description	The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of correct trials, ranging from 0-128. A higher score reflects a better outcome.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: correct trials
Baseline	74.5 (14.849)	68.857 (9.703)
16 weeks	67 (4.05)	69.667 (8.981)

8. Secondary Outcome

Title	Evaluation of Brain Injury as Assessed by the Trailmaking Test B Score
Description	The Trailmaking B score is the number of seconds spent connecting numbered circles (1-13) to circles containing letters of the alphabet (A-L) in alternating sequential order. A maximum of 300 seconds is allowed. Score ranges from 0-300. Higher score reflects poorer outcome.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: seconds
Baseline	68.411 (32.106)	71.432 (42.1)
16 weeks	56.439 (16.723)	68.015 (25.023)

9. Secondary Outcome

Title	Immediate Recall as Assessed by Hopkins Verbal Learning Test (HVLT)
Description	The Hopkins Verbal Learning Test (HVLT) consists of a 12-item word list, composed of four words from each of the three semantic categories. The subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The word list is then read to the subject at the approximate rate of one word every 2 seconds. This is done for three trials. The number of correctly-recalled words in each trial is recorded (maximum of 12). The score is a sum of all the correctly-recalled words from each trial, for a maximum score of 36.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: sum of correctly-recalled words
Baseline	23.077 (5.722)	25.938 (5.285)
16 weeks	23.538 (7.287)	25.5 (5.279)

10. Secondary Outcome

Title	Delayed Recall as Assessed by Hopkins Verbal Learning Test (HVLT)
Description	The HVLT consists of a 12-item word list, composed of four words from each of the three semantic categories. The subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The word list is then read to the subject at the approximate rate of one word every 2 seconds. This is done for three trials. After the third learning trial, the patient is read 24 words and is asked to say "yes" after each word that appeared on the recall list (12 targets) and "no" after each word that did not (12 distractors). Half of the distractors are drawn from the same semantic categories as the targets (related distractors) and half are drawn from other categories (unrelated distractors). The number of correctly-recalled words in each trial is recorded (maximum of 12 per trial). The score is the sum of all the correctly-recalled words from each trial, for a maximum of 36. T-scores are reported (average T-score of 50 (ranges 40-60)
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: T-score of correctly-recalled words
Baseline	44.364 (10.604)	43.071 (9.635)
16 weeks	49.111 (12.956)	47.692 (5.836)

11. Secondary Outcome

Title	Delayed Recall as Assessed by Brief Visual Memory Test (BVMT)
Description	BVMT is used to evaluate visuospatial memory abilities in neuropsychological populations. A visual display of six simple figures arranged in a 2 × 3 matrix on an 8 × 11 booklet is shown to participants for three consecutive 10-second trials. After each trial, participants are to draw as many designs as accurately as they can and in the correct location after a 25-minute delay filled with other distractor tasks. Scoring of the delayed recall is based on the accuracy of the drawings and the location of the figures. For each figure, one point is awarded to each satisfactory domain resulting in a maximum of 12-points per trial for a total score range of 0-36, with higher scores indicating a better outcome.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: accurately-drawn figures
Baseline	9.23 (2.713)	9.688 (3.005)
16 weeks	8.308 (3.066)	8.813 (2.509)

12. Secondary Outcome

Title	Immediate Recall as Assessed by Brief Visual Memory Test (BVMT)
Description	BVMT is used to evaluate visuospatial memory abilities in neuropsychological populations. A visual display of six simple figures arranged in a 2 × 3 matrix on an 8 × 11 booklet is shown to participants for three consecutive 10-second trials. After each trial, participants are to draw as many designs as accurately as they can and in the correct location. Scoring of the immediate recall is based on the accuracy of the drawings and the location of the figures. For each figure, one point is awarded to each satisfactory domain resulting in a maximum of 12-points per trial, for a total score ranging from 0-36, with a higher score reflecting a better outcome.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: accurately-drawn figures
Baseline	22.846 (9.547)	24.313 (7.355)
16 weeks	23.231 (8.833)	21.438 (6.593)

13. Secondary Outcome

Title	Evaluation of Brain Injury as Assessed by the Trailmaking Test A Score
Description	Trailmaking A is a psychological test with a score that is the number of seconds spent in connecting 25 numbered circles in sequential order. Score ranges from 0-150. Higher score reflects poorer outcome.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: seconds
Baseline	27.725 (8.285)	31.434 (10.02)
16 weeks	23.133 (5.8)	30.027 (12.642)

14. Secondary Outcome

Title	Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire
Description	The GAD-7 questionnaire is used as a screening tool and severity measure for generalized anxiety disorder. The scale ranges from 0 - 21. 0-4 = normal 5-9 = mild 10-14 = moderate >15 = severe
Time Frame	Baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	12.636 (4.61)	12.75 (5)
4 weeks	7.5 (6.375)	7.824 (5.028)
8 weeks	6.917 (6.417)	7.588 (5.874)
12 weeks	6.923 (5.423)	7.688 (5.594)
16 weeks	7.538 (6.603)	7.412 (5.853)

15. Secondary Outcome

Title	Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS)
Description	The DTS is a 17-item self-reported measure that assesses the 17 Diagnostic and Statistical Manual IV (DSM-IV) symptoms of post-traumatic stress disorder (PTSD). Items are rated on 5-point frequency (0 = "not at all" to 4 = "every day") and severity scales (0 = "not at all distressing" to 4 = "extremely distressing"). The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). The severity score will be used to assess this outcome.
Time Frame	Baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	34.154 (30.306)	41.706 (40.769)
4 weeks	15 (20.01)	24.063 (33.657)
8 weeks	11.462 (20.711)	17.294 (32.711)
12 weeks	14.833 (22.938)	27.125 (33.478)
16 weeks	16 (29.243)	18.647 (32.581)

16. Secondary Outcome

Title	Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI)
Description	The PSQI score scale ranges from 0-21. 0 = very good sleep quality 21 = very bad sleep quality A total score of "5" or greater is indicative of poor sleep quality (reflecting a higher level of fatigue)
Time Frame	Baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	13.846 (3.848)	13.688 (3.591)
4 weeks	10.23 (4.585)	10.647 (4.133)
8 weeks	9.846 (4.356)	10.176 (2.877)
12 weeks	9.5 (4.758)	10.235 (4.161)
16 weeks	9.154 (4.913)	9.625 (3.793)

17. Secondary Outcome

Title	Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS)
Description	The ESS is used to determine the level of daytime sleepiness. It is a questionnaire composed of 8 questions. The participant answers each question on a scale of 0 to 3 (0=no sleepiness, 1= mild sleepiness, 2= moderate sleepiness, 3= severe sleepiness). The total score is the sum of all responses for a maximum score of 24. A higher score reflects increased sleepiness.
Time Frame	Baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	9.769 (4.746)	9.412 (6.81)
4 weeks	5.846 (4.896)	7.563 (4.381)
8 weeks	5.923 (3.883)	6.063 (3.586)
12 weeks	6.667 (5.015)	7 (4.536)
16 weeks	6.077 (4.609)	6 (3.857)

18. Secondary Outcome

Title	Mean Cognitive Function as Assessed by the Montreal Cognitive Assessment (MOCA)
Description	MOCA is designed to assess cognitive impairment and Alzheimer's Disease. It is composed of the following: Visuospatial and Executive Functioning: 5 points Animal Naming: 3 points Attention: 6 points Language: 3 points Abstraction: 2 points Delayed Recall (Short-term Memory): 5 points Orientation: 6 points Education Level: 1 point is added to the test-taker's score if he or she has 12 years or less of formal education. Score ranges 0-31, with ≥ 26 being normal cognitive function. The lower the score, the greater the level of cognitive impairment.
Time Frame	Mean at baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	25.769 (2.619)	26.5 (3.141)
16 weeks	26 (3.342)	26.875 (3.442)

19. Secondary Outcome

Title	Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS)
Description	The NBRS is a 28-item interview which includes a test of orientation and memory for recent events, questions regarding emotional state, post-concussional symptoms, focused attention, and concentration (performing serial sevens), explanation of proverbs, tasks of planning and mental flexibility, and delayed recall of three objects presented at the beginning of a session. Observations are also made regarding the patient's fatigability, visible signs of anxiety, disinhibition, agitation, hostility, difficulties in expressive and receptive communication, and disturbance of mood. The balance of the items are rated according to the patient's performance on brief tasks and quality of answers to interview questions. Each of the 28 items are scored on a scale of 0 (not severe) to 6 (extremely severe), for a maximum score of 168. A higher score reflects increased severity of neuropsychiatric symptoms.
Time Frame	Mean at baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	51.23 (5.89)	56.125 (10.683)
4 weeks	40.545 (10.709)	40.727 (7.837)
8 weeks	44.222 (12.498)	42.786 (13.116)
12 weeks	43.222 (10.072)	39.273 (9.056)
16 weeks	39.154 (11.866)	40.375 (10.513)

20. Secondary Outcome

Title	Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ)
Description	Participants are asked to rate the severity of 16 different symptoms over the past 24 hours, on a severity scale from 0 to 4 (0 = not experienced, 1 = no more of a problem, 2 = mild problem, 3 = moderate problem, 4 = severe problem). The 16 symptoms include: headaches, dizziness, nausea and/or vomiting, hyperacusis, sleep disturbance, fatigue, being irritable, feeling depressed, feeling frustrated, forgetfulness, poor concentration, taking longer to think, blurred vision, light sensitivity, double vision, restlessness. Score ranges from 0 to 64, with a higher score reflecting increased severity of post-concussive symptoms.
Time Frame	Mean at baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	26.769 (8.719)	23.125 (14.184)
4 weeks	11.833 (8.747)	11.765 (9.451)
8 weeks	14.154 (11.753)	11 (8.075)
12 weeks	12.75 (12.009)	11.857 (10.369)
16 weeks	10.538 (7.817)	14.294 (14.886)

21. Secondary Outcome

Title	Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS)
Description	The FSS is a 9-item questionnaire which measures the severity of fatigue and how it interferes with certain activities. The items are scored on a 7-point scale with 1=strongly disagree and 7=strongly agree. The score ranges from 9 to a maximum of 63. A higher score reflects greater fatigue severity.
Time Frame	Mean at baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	28.308 (15.124)	41.176 (11.975)
4 weeks	28.385 (15.788)	23.375 (15.362)
8 weeks	20.769 (13.116)	29.938 (16.643)
12 weeks	23.25 (11.787)	27.286 (18.168)
16 weeks	21.23 (13.02)	29 (17.274)

22. Secondary Outcome

Title	Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS)
Description	MOAS measures four types of aggressive behavior as witnessed in the past week. Each section consists of five items, with the first section regarding verbal aggression, the second section focusing on aggression against property, the third section measuring autoaggression, and the fourth section concerning physical aggression. Participants are asked to check each item that is true over the last week. Items are allocated 0, 1, 2, 3 or 4 point(s), and then all points for each selected item are summed. The maximum total for each section is 10 if all items are selected. Total score ranges from 0-40 with a higher score indicating more aggressive behavior.
Time Frame	Mean at baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	2.308 (2.136)	3 (4.016)
4 weeks	1.308 (1.377)	1.118 (2.759)
8 weeks	0.692 (.855)	0.471 (1.068)
12 weeks	1.417 (2.429)	1 (1.932)
16 weeks	1.308 (2.213)	0.706 (1.312)

23. Secondary Outcome

Title	Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire
Description	The SWL is a 7-point Likert-style response scale. The possible range of scores is 5-35, with a score of 20 representing a neutral point on the scale. Scores between 5-9 indicate the respondent is extremely dissatisfied with life, whereas scores between 31-35 indicate the respondent is extremely satisfied.
Time Frame	Mean at baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	14.231 (7.132)	10.625 (4.015)
4 weeks	21.538 (8.511)	18.471 (8.769)
8 weeks	22.231 (8.207)	17.647 (9.88)
12 weeks	22 (8.524)	17 (8.809)
16 weeks	23.923 (6.898)	18.647 (9.367)

24. Secondary Outcome

Title	Presence of Social Connections as Assessed by the Social Ties Checklist (STC)
Description	The STC reflects the level of social contact. The score ranges from 0-10, with 0= excellent contact, 10=no contact. A higher score reflects poorer social contact.
Time Frame	Mean at baseline, 4, 8, 12, and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LFR rTMS	Sham Treatment
Arm/Group Description:	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.	Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	3.154 (1.573)	4.563 (2.065)
4 weeks	3.077 (1.706)	3.765 (1.855)
8 weeks	2.769 (1.536)	3.471 (1.7)
12 weeks	2.846 (1.573)	3.688 (2.243)
16 weeks	2.846 (1.676)	3.471 (2.065)

Adverse Events

Time Frame	Participants were assessed at follow-up visits at 4 weeks, 8 weeks, 12 weeks, and 16 weeks. Any Adverse Event up to 16 weeks is reported.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	LFR rTMS		Sham Treatment
Arm/Group Description	Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds. Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.		Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
All-Cause Mortality
	LFR rTMS		Sham Treatment
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/17 (0.00%)		0/17 (0.00%)
Serious Adverse Events
	LFR rTMS		Sham Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0.00%)		0/17 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	LFR rTMS		Sham Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/17 (35.29%)		7/17 (41.18%)
Blood and lymphatic system disorders
Other †	2/17 (11.76%)	8	2/17 (11.76%)	2
Nervous system disorders
Headache †	5/17 (29.41%)	12	5/17 (29.41%)	12
Dizziness †	1/17 (5.88%)	1	1/17 (5.88%)	2
Blurred Vision †	1/17 (5.88%)	1	0/17 (0.00%)	0
Tiredness †	1/17 (5.88%)	1	0/17 (0.00%)	0
Discomfort †	1/17 (5.88%)	1	1/17 (5.88%)	1
Face Twitching †	0/17 (0.00%)	0	1/17 (5.88%)	2
Eye Twitching †	1/17 (5.88%)	1	0/17 (0.00%)	0
Sleep Problem †	1/17 (5.88%)	1	1/17 (5.88%)	4
Psychiatric disorders
Depression †	1/17 (5.88%)	4	1/17 (5.88%)	1
Anxiety †	1/17 (5.88%)	1	1/17 (5.88%)	3
Skin and subcutaneous tissue disorders
Puff Face †	1/17 (5.88%)	1	0/17 (0.00%)	0
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Vani Rao, MD
• Organization: Johns Hopkins University School of Medicine
• Phone: 4105502288
• EMail: vrao@jhmi.edu

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02367521
• Other Study ID Numbers: NA_00090926
• First Submitted: February 9, 2015
• First Posted: February 20, 2015
• Results First Submitted: July 5, 2018
• Results First Posted: August 31, 2018
• Last Update Posted: August 31, 2018