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Therapeutic Efficacy of Transcranial Magnetic Stimulation in Schizophrenia

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ClinicalTrials.gov Identifier: NCT01551979
Recruitment Status : Completed
First Posted : March 13, 2012
Results First Posted : June 2, 2017
Last Update Posted : April 12, 2018
Sponsor:
Collaborator:
Sidney R. Baer, Jr. Foundation
Information provided by (Responsible Party):
Mark Halko, Beth Israel Deaconess Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Outcomes Assessor);   Primary Purpose: Treatment
Condition Schizophrenia
Intervention Device: Repetitive Transcranial Magnetic Stimulation
Enrollment 22
Recruitment Details  
Pre-assignment Details 22 patients gave informed consent for the study during the initial screening visit. After patients were found ineligible to participate following review of medical records, withdrew consent, or were lost to follow-up, only 17 remained for the randomization phase and started the study.
Arm/Group Title Active rTMS Sham rTMS
Hide Arm/Group Description

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Period Title: Overall Study
Started 10 7
Last Day of Treatment (After 5 Days) 10 7
1 Week Post Treatment 10 6
Completed 8 5
Not Completed 2 2
Arm/Group Title Active rTMS Sham rTMS Total
Hide Arm/Group Description

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Total of all reporting groups
Overall Number of Baseline Participants 10 7 17
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 7 participants 17 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
7
 100.0%
17
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 7 participants 17 participants
Female
2
  20.0%
2
  28.6%
4
  23.5%
Male
8
  80.0%
5
  71.4%
13
  76.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 7 participants 17 participants
10 7 17
1.Primary Outcome
Title Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Positive Subscale
Hide Description Therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) Positive Subscale, a 7 item subscale measuring the presence/absence and severity of positive symptoms of schizophrenia. The minimum score is 7 and the maximum score is 49, with higher values representing greater symptom severity. Change from baseline on the PANSS Positive Subscale can range from -42 to +42; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
Time Frame Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Participant drop out
Arm/Group Title Active rTMS Sham rTMS
Hide Arm/Group Description:

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Overall Number of Participants Analyzed 10 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
5 days of treatment - baseline Number Analyzed 10 participants 7 participants
-2.4  (3.565) -1.857  (1.574)
1 week post treatment - baseline Number Analyzed 9 participants 6 participants
-5.889  (3.333) -3.667  (3.724)
3 week post treatment - baseline Number Analyzed 8 participants 5 participants
-5  (4.504) -3  (3.317)
2.Primary Outcome
Title Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Negative Subscale
Hide Description Therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) Negative Subscale, a 7 item subscale measuring the presence/absence and severity of negative symptoms of schizophrenia. The minimum score is 7 and the maximum score is 49, with higher values representing greater symptom severity. Change from baseline on the PANSS Negative Subscale can range from -42 to +42; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
Time Frame Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Participant drop out
Arm/Group Title Active rTMS Sham rTMS
Hide Arm/Group Description:

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Overall Number of Participants Analyzed 10 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
5 days of treatment - baseline Number Analyzed 10 participants 7 participants
-1  (4.876) -1.571  (2.070)
1 week post treatment - baseline Number Analyzed 9 participants 6 participants
-3.889  (3.296) -1.667  (3.141)
3 week post treatment - baseline Number Analyzed 8 participants 5 participants
-3.5  (6.024) -0.2  (4.604)
3.Primary Outcome
Title Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) General Subscale
Hide Description Therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) General Subscale, a 16 item subscale measuring the presence/absence and severity of general psychopathology of schizophrenia. The minimum score is 16 and the maximum score is 112, with higher values representing greater psychopathology severity. Change from baseline on the PANSS General Subscale can range from -96 to +96; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
Time Frame Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Participant drop out
Arm/Group Title Active rTMS Sham rTMS
Hide Arm/Group Description:

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Overall Number of Participants Analyzed 10 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
5 days of treatment - baseline Number Analyzed 10 participants 7 participants
-3.1  (4.149) -2.714  (5.090)
1 week post treatment - baseline Number Analyzed 9 participants 6 participants
-8.222  (5.696) -2  (4.690)
3 week post treatment - baseline Number Analyzed 8 participants 5 participants
-7.375  (10.127) 0  (1)
4.Primary Outcome
Title Change From Baseline on the Clinical Global Impression (CGI) Severity of Illness
Hide Description Treatment response was evaluated with the Clinical Global Impressions (CGI) Scale, which is comprised of two companion one-item measures that use 7-point scales to evaluate severity of psychopathology and improvement from the initiation of treatment; each component is rated separately and the CGI does not yield a global score. The CGI Severity of Illness is a 7-point subscale in which a clinician rates the severity of the patient’s illness at the time of assessment. Ratings range from 1 to 7 and higher values represent more severe psychopathology: 1 indicates a normal and not at all ill patient and 7 indicates among the most extremely ill patients. Change from baseline on the CGI Severity of Illness subscale can range from -6 to +6, with negative values representing an improvement in psychopathology and positive values representing worsening psychopathology. Severity of Illness was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
Time Frame Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Participant drop out
Arm/Group Title Active rTMS Sham rTMS
Hide Arm/Group Description:

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Overall Number of Participants Analyzed 10 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
5 days of treatment - baseline Number Analyzed 10 participants 7 participants
-0.3  (0.483) -0.286  (0.488)
1 week post treatment - baseline Number Analyzed 10 participants 6 participants
-0.4  (0.699) -0.5  (0.548)
3 week post treatment - baseline Number Analyzed 8 participants 5 participants
-0.5  (0.535) -0.2  (0.837)
5.Primary Outcome
Title Clinical Global Impression (CGI) Global Improvement
Hide Description Treatment response was evaluated with the Clinical Global Impressions (CGI) Scale, which is comprised of two companion one-item measures that use 7-point scales to evaluate severity of psychopathology and improvement from the initiation of treatment; each component is rated separately and the CGI does not yield a global score. The CGI Global Improvement is a 7-point subscale in which a clinician assesses how much a patient’s illness has changed compared to baseline. Ratings range from 1 to 7, with 1 indicating very much improved and 7 indicating very much worse. Change from baseline on the CGI Global Improvement subscale can range from -6 to +6, with negative values representing an improvement in psychopathology and positive values representing worsening psychopathology. Global Improvement was assessed after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
Time Frame Last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Participant drop out
Arm/Group Title Active rTMS Sham rTMS
Hide Arm/Group Description:

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Overall Number of Participants Analyzed 10 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
5 days of treatment Number Analyzed 10 participants 7 participants
3.6  (0.516) 3.429  (1.134)
1 week post treatment Number Analyzed 10 participants 6 participants
3.3  (0.675) 4  (0.632)
3 week post treatment Number Analyzed 8 participants 5 participants
3.375  (0.518) 3.8  (0.447)
6.Secondary Outcome
Title Change From Baseline on the Calgary Depression Scale for Schizophrenia
Hide Description The Calgary Depression Scale for Schizophrenia is a 9-item scale that assesses depressive symptoms in patients with schizophrenia. Each item is rated separately and ratings range from 0 to 3. Higher values represent more severe depressive symptoms: 0 indicates an absent symptom and 3 indicates a severe symptom. The overall Calgary Depression Scale score is computed by summing each item. The total Calgary Depression Scale score ranges from 0 to 27, with higher values representing more severe depression in patients with schizophrenia. Change from baseline on the Calgary Depression Scale can range from -27 to +27, with negative values representing an improvement in depressive symptoms and positive values representing worsening depressive symptom severity. Depression was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
Time Frame Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Participant drop out
Arm/Group Title Active rTMS Sham rTMS
Hide Arm/Group Description:

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Overall Number of Participants Analyzed 10 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
5 days of treatment - baseline Number Analyzed 10 participants 6 participants
-2.6  (3.204) -1.167  (2.563)
1 week post treatment - baseline Number Analyzed 10 participants 6 participants
-2.7  (2.908) -1.833  (2.229)
3 week post treatment - baseline Number Analyzed 8 participants 5 participants
-2.25  (2.121) 0.8  (2.387)
Time Frame 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
Adverse Event Reporting Description 0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
 
Arm/Group Title Active rTMS Sham rTMS
Hide Arm/Group Description

High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

Sham rTMS to the vermis (lobule VII) of the cerebellum.

Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session.

Sham participants will undergo the same procedures as those in the active rTMS group.

All-Cause Mortality
Active rTMS Sham rTMS
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0      0/0    
Show Serious Adverse Events Hide Serious Adverse Events
Active rTMS Sham rTMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/10 (10.00%)      0/7 (0.00%)    
Psychiatric disorders     
Acute exacerbation of psychosis  [1]  1/10 (10.00%)  1 0/7 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Acute exacerbation of psychosis was assessed to be possibly related to participation in the study, but likely not related to the TMS. Subject was hospitalized.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Active rTMS Sham rTMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/10 (50.00%)      1/7 (14.29%)    
Cardiac disorders     
Blood pressure increase  [1]  1/10 (10.00%)  1 0/7 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Neck pain  [2]  3/10 (30.00%)  4 1/7 (14.29%)  1
Head heaviness  [3]  1/10 (10.00%)  3 0/7 (0.00%)  0
Nervous system disorders     
Discomfort with TMS  [4]  1/10 (10.00%)  1 0/7 (0.00%)  0
Headache  [5]  2/10 (20.00%)  2 1/7 (14.29%)  2
Change in energy level  [6]  1/10 (10.00%)  2 0/7 (0.00%)  0
Psychiatric disorders     
Change in mood  [7]  1/10 (10.00%)  1 0/7 (0.00%)  0
Skin and subcutaneous tissue disorders     
Scalp pain  [8]  0/10 (0.00%)  0 1/7 (14.29%)  2
Indicates events were collected by systematic assessment
[1]
Blood pressure elevation was assessed to be possibly related to the study.
[2]
Neck pain reported due to dystonia or heaviness of the coil. Neck pain due to dystonia was assessed as not related to study participation. Neck pain due to the coil was assessed as probably related to the study.
[3]
Heaviness was reported on right side of head during and after TMS. Headache was assessed to be possibly related to the study.
[4]
Discomfort with the TMS-EEG measures being done at baseline in the frontal lobe area. Discomfort was assessed to be related to the study.
[5]
Headaches were reported during EEG measures during baseline assessment, pre-TMS, and post-TMS. Headaches were assessed as possibly or probably related to the study.
[6]
Subject reported being mildly or moderately tired post-TMS.
[7]
Subject reported feeling depressed. Change in mood assessed to be possibly related to the study.
[8]
Scalp pain reported as pressure on scalp over the ears and top of head. Scalp pain was assessed as possibly related to the study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mark Halko
Organization: Beth Israel Deaconess Medical Center
Phone: 6176670367
EMail: mhalko@bidmc.harvard.edu
Publications:
Layout table for additonal information
Responsible Party: Mark Halko, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01551979     History of Changes
Other Study ID Numbers: 2011P000373
First Submitted: March 1, 2012
First Posted: March 13, 2012
Results First Submitted: March 15, 2017
Results First Posted: June 2, 2017
Last Update Posted: April 12, 2018