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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00453921
First received: March 27, 2007
Last updated: June 19, 2013
Last verified: June 2013

March 27, 2007
June 19, 2013
February 2007
May 2013   (final data collection date for primary outcome measure)
  • Neuropsychological Testing [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Self Report Questionnaires [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Structural and Functional MRI [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Neuropsychological Testing
  • Self Report Questionnaires
  • Structural and Functional MRI
Complete list of historical versions of study NCT00453921 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Methylphenidate (Ritalin) and Memory/Attention in Traumatic Brain Injury (TBI)
Methylphenidate (Ritalin) and Memory/Attention in Traumatic Brain Injury (TBI)

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.

Summary and Gaps to be Addressed by the Proposed Study

What is known: There are two interventions of promising efficacy in ameliorating deficits in attention and memory after mild traumatic brain injury (MTBI): (i) memory and attention training/rehabilitation, and (ii) catecholaminergic augmentation (particularly with methylphenidate - which augments both dopaminergic and adrenergic systems). fMRI and other functional imaging strategies are providing valuable insights into the underlying neural mechanisms of the cognitive enhancing effects of methylphenidate in some neuropsychiatric populations (individuals with ADHD), and the effects of cognitive rehabilitation efforts in some domains (e.g. speech and language in individuals after stroke).

What is not known: To date there are no studies that apply a psychopharmacological strategy of augmenting neurotransmitter systems known to modulate memory/attention (dopaminergic and adrenergic systems) in combination with a cognitive rehabilitation intervention known to improve memory/attention (memory/attention training) in individuals with MTBI. We are aware of no published studies that use fMRI to assess the neural mechanisms of memory/attention improvement from the use of catecholaminergic agents or memory/attention training in individuals with MTBI. It is important to determine the efficacy of combined memory/attention training and methylphenidate. It is equally important to begin to understand the neural mechanisms underlying effective treatment as it may help to inform the development of the next generation of interventions and perhaps lead to individually tailored treatment interventions. This proposal will start to address these gaps in our knowledge.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Brain Injury
  • Drug: Methylphenidate
    Dosage dependent on weight
  • Behavioral: Memory and Attention Training
    Weekly Memory and Attention Training with at home practice.
  • Other: Placebo as both treatments
    Placebo capsules and Placebo Memory and Attention Training
  • Placebo Comparator: 1
    Placebo Capsule and Placebo Memory and Attention Training
    Intervention: Other: Placebo as both treatments
  • Active Comparator: 2
    Methylphenidate capsules and Memory and Attention Training
    Interventions:
    • Drug: Methylphenidate
    • Behavioral: Memory and Attention Training
  • Active Comparator: 3
    Methylphenidate capsules and Placebo Memory and Attention Training
    Intervention: Drug: Methylphenidate
  • Active Comparator: 4
    Placebo capsules and Memory and Attention Training
    Intervention: Behavioral: Memory and Attention Training

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
160
May 2013
May 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age: Individuals aged 18-65 who sustained a mild to severe TBI 4 months prior to study entry.
  2. 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.
  3. 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:

  1. a history of other neurologic disorders (such as epilepsy, cerebrovascular disease, mental retardation, neurodegenerative disorders)
  2. significant systemic medical illness such as clinically significant liver disease, renal disease, atherosclerotic coronary vascular disease, or hypertension requiring medication management
  3. 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
  4. women currently pregnant or lactating. Female participants will be asked to take a pregnancy test to confirm they are not currently pregnant.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00453921
17363, 5R01HD047242
Yes
Dartmouth-Hitchcock Medical Center
Dartmouth-Hitchcock Medical Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Thomas W McAllister, MD Dartmouth-Hitchcock Medical Center, Dartmouth Medical School
Dartmouth-Hitchcock Medical Center
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP