Trial Outcomes & Findings for Methylphenidate (Ritalin) and Memory/Attention in Traumatic Brain Injury (TBI) (NCT NCT00453921)

Last Updated: 2018-06-13

Results Overview

Memory measure: California Verbal Learning Test, 2nd edition (CVLT), Total, trials 1-5 (range: 0-80). Higher scores are better outcome.

Recruitment status

COMPLETED

Study phase

Target enrollment

76 participants

Primary outcome timeframe

post-intervention (at least 7 weeks)

Results posted on

2018-06-13

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Both Conditions Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions) Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy 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.	Active Drug/Placebo Therapy Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy) Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy 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 Study STARTED	19	18	20	19
Overall Study COMPLETED	18	17	18	18
Overall Study NOT COMPLETED	1	1	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Both Conditions Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions) Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy 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.	Active Drug/Placebo Therapy Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy) Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy 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 Study Withdrawal by Subject	1	1	1	1
Overall Study Lost to Follow-up	0	0	1	0

Baseline Characteristics

One participant withdrew from study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Both Conditions n=19 Participants Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy n=18 Participants Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Active Drug/Placebo Therapy n=20 Participants Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy n=19 Participants Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Total n=76 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 14.2 • n=19 Participants • One participant withdrew from study	43.1 years STANDARD_DEVIATION 12.3 • n=18 Participants • One participant withdrew from study	43.0 years STANDARD_DEVIATION 15.0 • n=20 Participants • One participant withdrew from study	37.2 years STANDARD_DEVIATION 12.0 • n=18 Participants • One participant withdrew from study	40.1 years STANDARD_DEVIATION 13.3 • n=75 Participants • One participant withdrew from study
Sex: Female, Male Female	6 Participants n=19 Participants • One participant withdrew from study	10 Participants n=18 Participants • One participant withdrew from study	6 Participants n=20 Participants • One participant withdrew from study	4 Participants n=18 Participants • One participant withdrew from study	26 Participants n=75 Participants • One participant withdrew from study
Sex: Female, Male Male	13 Participants n=19 Participants • One participant withdrew from study	8 Participants n=18 Participants • One participant withdrew from study	14 Participants n=20 Participants • One participant withdrew from study	14 Participants n=18 Participants • One participant withdrew from study	49 Participants n=75 Participants • One participant withdrew from study
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=19 Participants • One participant discontinued participation	1 Participants n=18 Participants • One participant discontinued participation	0 Participants n=20 Participants • One participant discontinued participation	1 Participants n=18 Participants • One participant discontinued participation	2 Participants n=75 Participants • One participant discontinued participation
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=19 Participants • One participant discontinued participation	17 Participants n=18 Participants • One participant discontinued participation	20 Participants n=20 Participants • One participant discontinued participation	17 Participants n=18 Participants • One participant discontinued participation	73 Participants n=75 Participants • One participant discontinued participation
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=20 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=75 Participants • One participant discontinued participation
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=19 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=20 Participants • One participant discontinued participation	1 Participants n=18 Participants • One participant discontinued participation	1 Participants n=75 Participants • One participant discontinued participation
Race (NIH/OMB) Asian	0 Participants n=19 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=20 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=75 Participants • One participant discontinued participation
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=19 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=20 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=75 Participants • One participant discontinued participation
Race (NIH/OMB) Black or African American	0 Participants n=19 Participants • One participant discontinued participation	1 Participants n=18 Participants • One participant discontinued participation	1 Participants n=20 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	2 Participants n=75 Participants • One participant discontinued participation
Race (NIH/OMB) White	19 Participants n=19 Participants • One participant discontinued participation	17 Participants n=18 Participants • One participant discontinued participation	19 Participants n=20 Participants • One participant discontinued participation	17 Participants n=18 Participants • One participant discontinued participation	72 Participants n=75 Participants • One participant discontinued participation
Race (NIH/OMB) More than one race	0 Participants n=19 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=20 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=75 Participants • One participant discontinued participation
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=20 Participants • One participant discontinued participation	0 Participants n=18 Participants • One participant discontinued participation	0 Participants n=75 Participants • One participant discontinued participation
Region of Enrollment United States	19 Participants n=19 Participants • One participant discontinued	18 Participants n=18 Participants • One participant discontinued	20 Participants n=20 Participants • One participant discontinued	18 Participants n=18 Participants • One participant discontinued	75 Participants n=75 Participants • One participant discontinued

PRIMARY outcome

Timeframe: post-intervention (at least 7 weeks)

Memory measure: California Verbal Learning Test, 2nd edition (CVLT), Total, trials 1-5 (range: 0-80). Higher scores are better outcome.

Outcome measures

Outcome measures
Measure	Placebo Both Conditions n=18 Participants Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy n=17 Participants Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Active Drug/Placebo Therapy n=19 Participants Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy n=17 Participants Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Neuropsychological Assessment, CVLT-II	51.3 units on a scale Standard Deviation 1.9	51.8 units on a scale Standard Deviation 2.1	51.9 units on a scale Standard Deviation 1.9	57.2 units on a scale Standard Deviation 2.0

PRIMARY outcome

Timeframe: post-intervention (at least 7 weeks)

Continuous Performance Test, Distractibility Condition (Reaction Time in msecs) (range: 0-800). Higher score is worse performance.

Outcome measures

Outcome measures
Measure	Placebo Both Conditions n=18 Participants Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy n=17 Participants Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Active Drug/Placebo Therapy n=19 Participants Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy n=18 Participants Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Neuropsychological Assessment - CPT, Distractibility Condition (Reaction Time)	426.4 units on a scale Standard Deviation 15.3	394.7 units on a scale Standard Deviation 17.3	416.6 units on a scale Standard Deviation 15.9	413.0 units on a scale Standard Deviation 17.3

PRIMARY outcome

Timeframe: pre- to post-6 week treatment intervention (at least 7 weeks)

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.

Outcome measures

Outcome measures
Measure	Placebo Both Conditions n=12 Participants Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy n=10 Participants Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Active Drug/Placebo Therapy n=10 Participants Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy n=10 Participants Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Functional MRI Task Performance and Brain Activation (Change From Baseline to Post-treatment)	-4.46 percentage of correct targets (adjusted) Standard Deviation 30.8	4.69 percentage of correct targets (adjusted) Standard Deviation 26.8	4.86 percentage of correct targets (adjusted) Standard Deviation 29.5	-0.36 percentage of correct targets (adjusted) Standard Deviation 23.4

PRIMARY outcome

Timeframe: pre- to post-intervention (at least 7 weeks)

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.

Outcome measures

Outcome measures
Measure	Placebo Both Conditions n=12 Participants Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy n=10 Participants Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Active Drug/Placebo Therapy n=10 Participants Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy n=10 Participants Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Change in Anterior Cingulate Gyrus Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention	-0.31 units on a scale Standard Deviation .36	0.09 units on a scale Standard Deviation .36	0.20 units on a scale Standard Deviation .42	0.05 units on a scale Standard Deviation .27

PRIMARY outcome

Timeframe: pre- to post-treatment (at least 7 weeks)

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.

Outcome measures

Outcome measures
Measure	Placebo Both Conditions n=12 Participants Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy n=10 Participants Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Active Drug/Placebo Therapy n=10 Participants Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy n=10 Participants Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Change in Left Middle/Inferior Frontal Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention	-0.16 units on a scale Standard Deviation .20	0.04 units on a scale Standard Deviation .15	0.07 units on a scale Standard Deviation .24	.10 units on a scale Standard Deviation .21

PRIMARY outcome

Timeframe: pre- to post-treatment (at least 7 weeks)

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.

Outcome measures

Outcome measures
Measure	Placebo Both Conditions n=12 Participants Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy n=10 Participants Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Active Drug/Placebo Therapy n=10 Participants Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy n=10 Participants Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Change in Right Inferior Frontal Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention	-0.18 units on a scale Standard Deviation .28	0.05 units on a scale Standard Deviation .28	.15 units on a scale Standard Deviation .29	.14 units on a scale Standard Deviation .22

SECONDARY outcome

Timeframe: post-intervention (at least 7 weeks)

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.

Outcome measures

Outcome measures
Measure	Placebo Both Conditions n=19 Participants Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Drug/Active Therapy n=18 Participants Methylphenidate: Dosage dependent on weight Memory and Attention Training: Weekly Memory and Attention Training with at home practice.	Active Drug/Placebo Therapy n=20 Participants Methylphenidate: Dosage dependent on weight	Placebo Drug/Active Therapy n=18 Participants Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Self Report Questionnaire - MASQ	116.4 units on a scale Standard Deviation 4.5	120.5 units on a scale Standard Deviation 4.8	114.1 units on a scale Standard Deviation 4.5	118.1 units on a scale Standard Deviation 4.8

Adverse Events

Placebo Both Conditions

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Active Med/Active Therapy

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Active Med/Placebo Therapy

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo Med/Active Therapy

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo Both Conditions n=19 participants at risk Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions) Placebo as both treatments: Placebo capsules and Placebo Memory and Attention Training	Active Med/Active Therapy n=18 participants at risk 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.	Active Med/Placebo Therapy n=20 participants at risk Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy) Methylphenidate: Dosage dependent on weight	Placebo Med/Active Therapy n=18 participants at risk Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy) Memory and Attention Training: Weekly Memory and Attention Training with at home practice.
Gastrointestinal disorders Abdominal discomfort	5.3% 1/19 • Number of events 2 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	38.9% 7/18 • Number of events 18 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	30.0% 6/20 • Number of events 14 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	11.1% 2/18 • Number of events 5 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Nervous system disorders headache	31.6% 6/19 • Number of events 9 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	61.1% 11/18 • Number of events 20 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	35.0% 7/20 • Number of events 16 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	44.4% 8/18 • Number of events 12 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Nervous system disorders Insomnia	26.3% 5/19 • Number of events 12 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	38.9% 7/18 • Number of events 14 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	20.0% 4/20 • Number of events 6 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	16.7% 3/18 • Number of events 6 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Psychiatric disorders Nervousness	10.5% 2/19 • Number of events 4 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	38.9% 7/18 • Number of events 20 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	30.0% 6/20 • Number of events 15 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	11.1% 2/18 • Number of events 4 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Gastrointestinal disorders loss of appetite	5.3% 1/19 • Number of events 2 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	44.4% 8/18 • Number of events 30 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	25.0% 5/20 • Number of events 18 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	16.7% 3/18 • Number of events 6 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Cardiac disorders palpitations	5.3% 1/19 • Number of events 1 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	22.2% 4/18 • Number of events 5 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	25.0% 5/20 • Number of events 5 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	5.6% 1/18 • Number of events 1 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
General disorders dry mouth	0.00% 0/19 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	11.1% 2/18 • Number of events 5 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	15.0% 3/20 • Number of events 8 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	0.00% 0/18 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Gastrointestinal disorders Nausea	10.5% 2/19 • Number of events 6 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	27.8% 5/18 • Number of events 9 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	25.0% 5/20 • Number of events 11 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	16.7% 3/18 • Number of events 5 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Gastrointestinal disorders Vomiting	5.3% 1/19 • Number of events 1 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	11.1% 2/18 • Number of events 4 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	10.0% 2/20 • Number of events 3 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	5.6% 1/18 • Number of events 1 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Nervous system disorders Dizziness	10.5% 2/19 • Number of events 2 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	22.2% 4/18 • Number of events 6 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	20.0% 4/20 • Number of events 5 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	16.7% 3/18 • Number of events 4 • 6 years Physical Symptom Checklist was completed at each visit and phone call.
Psychiatric disorders Depressed mood	15.8% 3/19 • Number of events 8 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	33.3% 6/18 • Number of events 18 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	15.0% 3/20 • Number of events 14 • 6 years Physical Symptom Checklist was completed at each visit and phone call.	11.1% 2/18 • Number of events 8 • 6 years Physical Symptom Checklist was completed at each visit and phone call.

Additional Information

Dr. Laura Flashman

Dartmouth Hitchcock Medical Center

Phone: 6036505824

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place