N/A
N=76
Methylphenidate (Ritalin) and Memory/Attention in Traumatic Brain Injury (TBI)
Brain Injury
Bottom Line
View on ClinicalTrials.gov: NCT00453921 ↗Enrolled (actual)
76
Serious AEs
0.0%
Results posted
Jun 2018
Primary outcome: Primary: Neuropsychological Assessment, CVLT-II — 51.3; 51.8; 51.9; 57.2 units on a scale — p=<0.04
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Methylphenidate (Drug); Memory and Attention Training (Behavioral); Placebo as both treatments (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Dartmouth-Hitchcock Medical Center
- Primary completion
- May 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Neuropsychological Assessment, CVLT-II |
51.3; 51.8; 51.9; 57.2 | <0.04 sig |
| PRIMARY Neuropsychological Assessment - CPT, Distractibility Condition (Reaction Time) |
426.4; 394.7; 416.6; 413.0 | — |
| PRIMARY Functional MRI Task Performance and Brain Activation (Change From Baseline to Post-treatment) |
-4.46; 4.69; 4.86; -0.36 | <0.05 sig |
| PRIMARY Change in Anterior Cingulate Gyrus Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention |
-0.31; 0.09; 0.20; 0.05 | <0.05 sig |
| PRIMARY Change in Left Middle/Inferior Frontal Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention |
-0.16; 0.04; 0.07; .10 | — |
| PRIMARY Change in Right Inferior Frontal Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention |
-0.18; 0.05; .15; .14 | — |
| SECONDARY Self Report Questionnaire - MASQ |
116.4; 120.5; 114.1; 118.1 | <0.01 sig |
Summary
Traumatic brain injury (TBI) is a significant public health problem, with 1.5-2.0 million Americans injured each year. Cognitive deficits, particularly in the domains of memory and attention are frequently the source of lingering disability after TBI and a source of enormous distress to the injured individuals and their family/caregivers. To date, interventions to ameliorate chronic cognitive deficits have been directed at either pharmacological interventions or cognitive rehabilitation. We propose to (1) To compare the efficacy of three interventions: memory and attention training (MAAT), methylphenidate, and memory/attention training in combination with methylphenidate and (2) use functional MRI (fMRI) to characterize changes in activation of the neural circuitry of memory and attention due to MAAT alone, methylphenidate alone, and MAAT in combination with methylphenidate. This is a two by two design with medication (methylphenidate/placebo) and cognitive therapy (Memory and Attention Training (MAAT) or an Attention control intervention) as possible interventions. Using a randomized, placebo-controlled, double-blind design, 200 individuals with persistent cognitive deficits 6-12 months after MTBI will be randomized to receive a six week trial of either (1) MAAT and placebo, (2) MAAT and methylphenidate (0.3 mg/kg BID), (3) attention control intervention and methylphenidate (0.3 mg/kg BID), or (4) attention control intervention and placebo. Symptom distress, attention and memory performance, and activation patterns of the neural circuitry of attention and memory while undergoing fMRI will be characterized at baseline, and after the four treatment conditions. This study will provide important information on three interventions for the most disabling sequelae of an enormous public health problem. Further, it will help to clarify underlying neural mechanisms and suggest additional treatment possibilities.
Eligibility Criteria
Inclusion Criteria
- Age: Individuals aged 18-65 who sustained a mild to severe TBI 4 months prior to study entry.
- TBI: Subjects must sustain a traumatic blow to the head, resulting in either alteration of level of consciousness (manifested by being dazed and confused or having amnesia for the event) or loss of consciousness (LOC). Duration of LOC will be estimated by using all available information including patient and witness reports, emergency personnel records and Dartmouth Hitchcock Medical Center (DHMC) medical records. Post traumatic amnesia (PTA) will be estimated by careful questioning of patients to determine the time of return of continuous memory. This will be informed by review of medical records. We plan to include individuals with intracranial or skull injuries stemming from the TBI, providing they meet the inclusion criteria. Such lesions will be catalogued, and included as a factor in the data analysis.
- Cognitive Deficits: Subjects will have either subjective and objective evidence of persistent cognitive deficits. Subjects must report persistent memory or attention deficits as a result of their injury, which are of sufficient severity to interfere with social and/or occupational functioning. Subjects must either score more than 2 standard deviations below the age adjusted norm or estimates of baseline premorbid function on one or more tests of attention and/or memory administered as part of the baseline screening cognitive battery (see below), or score greater than 1.0 standard deviations below either age adjusted norms or estimates of premorbid function on 2 or more of the screening tests.
Exclusion Criteria
The following factors will exclude otherwise eligible subjects from participation:
- a history of other neurologic disorders (such as epilepsy, cerebrovascular disease, mental retardation, neurodegenerative disorders)
- significant systemic medical illness such as clinically significant liver disease, renal disease, atherosclerotic coronary vascular disease, or hypertension requiring medication management
- current Diagnostic and Statistical Manual (DSM-IV) Axis I diagnosis of psychiatric illness other than substance abuse. We have given careful consideration to the inclusion of the latter group given our use of a stimulant with potential abuse properties. Because of the potential for cross-over abuse with cocaine, amphetamines, and other stimulants, individuals with such histories will be excluded from this study. Individuals with history of otherwise uncomplicated ethanol or other non-stimulant drug abuse currently in stable remission will be eligible. The Structured Clinical Interview for DSM-IV (MINI) will be used to screen for psychiatric illness
- women currently pregnant or lactating. Female participants will be asked to take a pregnancy test to confirm they are not currently pregnant.
Data sourced from ClinicalTrials.gov (NCT00453921). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.