Methylphenidate (Ritalin) and Memory/Attention in Traumatic Brain Injury (TBI)
Condition: Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Study type: Interventional

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.
    

Detailed description: 
      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.
    

Intervention name(s): Methylphenidate; Memory and Attention Training; Placebo as both treatments
Intervention type(s): Drug; Behavioral; Other
Intervention description(s): Dosage dependent on weight; Weekly Memory and Attention Training with at home practice.; Placebo capsules and Placebo Memory and Attention Training
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: TBI; Memory; Methylphenidate; Ritalin; Memory and Attention Training