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Methylphenidate (Ritalin) and Memory/Attention in Traumatic Brain Injury (TBI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00453921
Recruitment Status : Completed
First Posted : March 29, 2007
Results First Posted : June 7, 2018
Last Update Posted : June 13, 2018
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Laura Flashman, Dartmouth-Hitchcock Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Brain Injury
Interventions Drug: Methylphenidate
Behavioral: Memory and Attention Training
Other: Placebo as both treatments
Enrollment 76
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy
Hide Arm/Group Description

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Methylphenidate: Dosage dependent on weight

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Period Title: Overall Study
Started 19 18 20 19
Completed 18 17 18 18
Not Completed 1 1 2 1
Reason Not Completed
Withdrawal by Subject             1             1             1             1
Lost to Follow-up             0             0             1             0
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy Total
Hide Arm/Group Description Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice. Total of all reporting groups
Overall Number of Baseline Participants 19 18 20 19 76
Hide Baseline Analysis Population Description
Individuals age 18-65 with a traumatic brain injury of at least mild severity at least 4 months prior to study entry, with self-report of cognitive deficits as a result of the injury of sufficient severity to interfere with social and/or occupational functioning.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 18 participants 20 participants 18 participants 75 participants
37.3  (14.2) 43.1  (12.3) 43.0  (15.0) 37.2  (12.0) 40.1  (13.3)
[1]
Measure Analysis Population Description: One participant withdrew from study
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 18 participants 20 participants 18 participants 75 participants
Female
6
  31.6%
10
  55.6%
6
  30.0%
4
  22.2%
26
  34.7%
Male
13
  68.4%
8
  44.4%
14
  70.0%
14
  77.8%
49
  65.3%
[1]
Measure Analysis Population Description: One participant withdrew from study
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 18 participants 20 participants 18 participants 75 participants
Hispanic or Latino
0
   0.0%
1
   5.6%
0
   0.0%
1
   5.6%
2
   2.7%
Not Hispanic or Latino
19
 100.0%
17
  94.4%
20
 100.0%
17
  94.4%
73
  97.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: One participant discontinued participation
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 18 participants 20 participants 18 participants 75 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.6%
1
   1.3%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   5.6%
1
   5.0%
0
   0.0%
2
   2.7%
White
19
 100.0%
17
  94.4%
19
  95.0%
17
  94.4%
72
  96.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: One participant discontinued participation
Region of Enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 19 participants 18 participants 20 participants 18 participants 75 participants
19
 100.0%
18
 100.0%
20
 100.0%
18
 100.0%
75
 100.0%
[1]
Measure Analysis Population Description: One participant discontinued
1.Primary Outcome
Title Neuropsychological Assessment, CVLT-II
Hide Description Memory measure: California Verbal Learning Test, 2nd edition (CVLT), Total, trials 1-5 (range: 0-80). Higher scores are better outcome.
Time Frame post-intervention (at least 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy
Hide Arm/Group Description:
Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate: Dosage dependent on weight
Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Overall Number of Participants Analyzed 18 17 19 17
Mean (Standard Deviation)
Unit of Measure: units on a scale
51.3  (1.9) 51.8  (2.1) 51.9  (1.9) 57.2  (2.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Both Conditions, Active Drug/Active Therapy, Active Drug/Placebo Therapy, Placebo Drug/Active Therapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.04
Comments For active therapy/placebo relative to both placebo
Method Kruskal-Wallis
Comments [Not Specified]
2.Primary Outcome
Title Neuropsychological Assessment - CPT, Distractibility Condition (Reaction Time)
Hide Description Continuous Performance Test, Distractibility Condition (Reaction Time in msecs) (range: 0-800). Higher score is worse performance.
Time Frame post-intervention (at least 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy
Hide Arm/Group Description:

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Methylphenidate: Dosage dependent on weight

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Overall Number of Participants Analyzed 18 17 19 18
Mean (Standard Deviation)
Unit of Measure: units on a scale
426.4  (15.3) 394.7  (17.3) 416.6  (15.9) 413.0  (17.3)
3.Primary Outcome
Title Functional MRI Task Performance and Brain Activation (Change From Baseline to Post-treatment)
Hide Description Change in performance (percent correct,adjusted for guessing) from pre-(baseline) to post-treatment (approximately 7 weeks) for in-scanner n-back working memory task (Range: 0-100). Higher scores means better performance.
Time Frame pre- to post-6 week treatment intervention (at least 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy
Hide Arm/Group Description:

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Methylphenidate: Dosage dependent on weight

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Overall Number of Participants Analyzed 12 10 10 10
Mean (Standard Deviation)
Unit of Measure: percentage of correct targets (adjusted)
-4.46  (30.8) 4.69  (26.8) 4.86  (29.5) -0.36  (23.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Both Conditions, Active Drug/Active Therapy, Active Drug/Placebo Therapy, Placebo Drug/Active Therapy
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Looking for statistical difference, p < .01, between groups looking at change scores
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
4.Primary Outcome
Title Change in Anterior Cingulate Gyrus Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention
Hide Description Change from pre- to post-treatment in brain activation in the anterior cingulate region of interest in arbitrary units provided by the SPM (statistical parametric mapping) program (range: unknown). Higher scores indicate greater increase in activation from pre- to post-treatment.
Time Frame pre- to post-intervention (at least 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy
Hide Arm/Group Description:

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Methylphenidate: Dosage dependent on weight

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Overall Number of Participants Analyzed 12 10 10 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.31  (.36) 0.09  (.36) 0.20  (.42) 0.05  (.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Both Conditions, Active Drug/Active Therapy, Active Drug/Placebo Therapy, Placebo Drug/Active Therapy
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments group differences
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
5.Primary Outcome
Title Change in Left Middle/Inferior Frontal Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention
Hide Description Change from pre- to post-treatment in brain activation in the left middle/inferior frontal region of interest in arbitrary units provided by the SPM (statistical parametric mapping) program (range: unknown). Higher scores indicate greater increase in activation from pre- to post-treatment.
Time Frame pre- to post-treatment (at least 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy
Hide Arm/Group Description:

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Methylphenidate: Dosage dependent on weight

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Overall Number of Participants Analyzed 12 10 10 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.16  (.20) 0.04  (.15) 0.07  (.24) .10  (.21)
6.Primary Outcome
Title Change in Right Inferior Frontal Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention
Hide Description Change from pre- to post-treatment in brain activation in the right inferior frontal region of interest in arbitrary units provided by the SPM (statistical parametric mapping) program (range: unknown). Higher scores indicate greater increase in activation from pre- to post-treatment.
Time Frame pre- to post-treatment (at least 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy
Hide Arm/Group Description:

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Methylphenidate: Dosage dependent on weight

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Overall Number of Participants Analyzed 12 10 10 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.18  (.28) 0.05  (.28) .15  (.29) .14  (.22)
7.Secondary Outcome
Title Self Report Questionnaire - MASQ
Hide Description The Multiple Abilities Questionnaire (self rating) is a questionnaire in which participants can identify deficits/complaints in the areas of language, visual perception, verbal memory, visual memory and attention and concentration. A total score is calculated; range is 30-130. Higher scores indicate greater level of complaints (worse outcome). For the purposes of this study, a score one standard deviation above the mean (102.7) indicated significant reported cognitive complaints.
Time Frame post-intervention (at least 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Both Conditions Active Drug/Active Therapy Active Drug/Placebo Therapy Placebo Drug/Active Therapy
Hide Arm/Group Description:

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Methylphenidate: Dosage dependent on weight

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Overall Number of Participants Analyzed 19 18 20 18
Mean (Standard Deviation)
Unit of Measure: units on a scale
116.4  (4.5) 120.5  (4.8) 114.1  (4.5) 118.1  (4.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Both Conditions, Active Drug/Active Therapy, Active Drug/Placebo Therapy, Placebo Drug/Active Therapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Both Conditions, Active Drug/Active Therapy, Active Drug/Placebo Therapy, Placebo Drug/Active Therapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments a priopr
Method ANCOVA
Comments [Not Specified]
Time Frame 6 years
Adverse Event Reporting Description Physical Symptom Checklist was completed at each visit and phone call.
 
Arm/Group Title Placebo Both Conditions Active Med/Active Therapy Active Med/Placebo Therapy Placebo Med/Active Therapy
Hide Arm/Group Description

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Methylphenidate: Dosage dependent on weight

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Methylphenidate: Dosage dependent on weight

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Memory and Attention Training: Weekly Memory and Attention Training with at home practice.

All-Cause Mortality
Placebo Both Conditions Active Med/Active Therapy Active Med/Placebo Therapy Placebo Med/Active Therapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)      0/18 (0.00%)      0/20 (0.00%)      0/18 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Both Conditions Active Med/Active Therapy Active Med/Placebo Therapy Placebo Med/Active Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/19 (0.00%)      0/18 (0.00%)      0/20 (0.00%)      0/18 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Both Conditions Active Med/Active Therapy Active Med/Placebo Therapy Placebo Med/Active Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/19 (42.11%)      12/18 (66.67%)      11/20 (55.00%)      9/18 (50.00%)    
Cardiac disorders         
palpitations   1/19 (5.26%)  1 4/18 (22.22%)  5 5/20 (25.00%)  5 1/18 (5.56%)  1
Gastrointestinal disorders         
Abdominal discomfort   1/19 (5.26%)  2 7/18 (38.89%)  18 6/20 (30.00%)  14 2/18 (11.11%)  5
loss of appetite   1/19 (5.26%)  2 8/18 (44.44%)  30 5/20 (25.00%)  18 3/18 (16.67%)  6
Nausea   2/19 (10.53%)  6 5/18 (27.78%)  9 5/20 (25.00%)  11 3/18 (16.67%)  5
Vomiting   1/19 (5.26%)  1 2/18 (11.11%)  4 2/20 (10.00%)  3 1/18 (5.56%)  1
General disorders         
dry mouth   0/19 (0.00%)  0 2/18 (11.11%)  5 3/20 (15.00%)  8 0/18 (0.00%)  0
Nervous system disorders         
headache   6/19 (31.58%)  9 11/18 (61.11%)  20 7/20 (35.00%)  16 8/18 (44.44%)  12
Insomnia   5/19 (26.32%)  12 7/18 (38.89%)  14 4/20 (20.00%)  6 3/18 (16.67%)  6
Dizziness   2/19 (10.53%)  2 4/18 (22.22%)  6 4/20 (20.00%)  5 3/18 (16.67%)  4
Psychiatric disorders         
Nervousness   2/19 (10.53%)  4 7/18 (38.89%)  20 6/20 (30.00%)  15 2/18 (11.11%)  4
Depressed mood   3/19 (15.79%)  8 6/18 (33.33%)  18 3/20 (15.00%)  14 2/18 (11.11%)  8
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Laura Flashman
Organization: Dartmouth Hitchcock Medical Center
Phone: 6036505824
EMail: Laura.A.Flashman@hitchcock.org
Publications:
Layout table for additonal information
Responsible Party: Laura Flashman, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00453921     History of Changes
Other Study ID Numbers: 17363
5R01HD047242 ( U.S. NIH Grant/Contract )
First Submitted: March 27, 2007
First Posted: March 29, 2007
Results First Submitted: March 14, 2018
Results First Posted: June 7, 2018
Last Update Posted: June 13, 2018