Rivastigmine Patch in Veterans With Cognitive Impairment Following TBI
Condition: Traumatic Brain Injury; Cognitive Impairment
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 3

Summary: 
      Difficulties with intellectual functioning, particularly memory functions, are common and
      source of long-term disability after Traumatic Brain Injury (TBI). However, there is very
      little information about pharmacologic (i.e., medication) treatments targeting these
      deficits. There are growing data showing brain abnormalities in acetylcholine, the chemical
      system that manages memory, in TBI. These findings provide the rationale for the use of
      cholinesterase inhibitors, medications that modulate this system, in TBI patients. As the
      prevalence of TBI among Veterans of recent military conflicts increases, becoming a
      "signature injury" of the Iraq and Afghanistan conflicts, it is of utmost importance to the
      Veterans Health Administration to collect scientific data on the efficacy of pharmacological
      treatments for intellectual difficulties in TBI patients. This study will evaluate the
      effects of the cholinesterase inhibitor rivastigmine transdermal patch in Veterans with TBI
      and posttraumatic memory problems. Results will provide much needed data that will help treat
      Veterans with TBI.
    

Detailed description: 
      Traumatic brain injury (TBI) represents one of the most significant health risks related to
      military duty; rapidly becoming the "signature injury" of the Iraq and Afghanistan conflicts.
      TBI patients often experience multiple cognitive problems, with disturbances in memory,
      attention, and executive functions among the most common. Disturbances in memory as well as
      attention are particularly problematic, as disruption of these relatively basic cognitive
      functions may exacerbate or cause additional disturbances in executive function,
      communication and other more complex cognitive domains. These cognitive deficits, especially
      when memory is affected, significantly impact day-to-day functioning and are the source of
      lingering disability and distress to the affected individuals. However, despite advances made
      in TBI care, treatment of cognitive deficits in TBI lag behind, forcing clinicians to provide
      treatment without the guidance of evidence-based scientific data. This proposal aims to begin
      the process of providing clinicians with evidence-based guidelines for pharmacological
      management of Veterans with TBI suffering from persistent cognitive deficits following their
      injuries. This aim will be accomplished by conducting a clinical trial in Veterans suffering
      from moderate to severe posttraumatic memory impairment following TBI. Specifically, this
      proposal will evaluate the efficacy and safety of rivastigmine transdermal patch, an
      intermediate-acting cholinesterase inhibitor, in this population.

      The investigators hypothesize that rivastigmine transdermal patch will be more effective
      than, and equally safe as, placebo in the treatment of moderate to severe posttraumatic
      memory impairment in Veterans with TBI when tested in a randomized, multi-site, parallel
      design, placebo-controlled trial, at a 12-week endpoint. The exploratory hypothesis states
      that compared to placebo, rivastigmine patch will be more effective and equally safe in the
      treatment of patients who will continue in a randomized, placebo-controlled phase for a total
      of 26 weeks. To test these hypotheses we will evaluate the effect and the safety of
      rivastigmine 9.5 mg/24 hours (10cm2) transdermal patch in 138 Veterans who meet or exceed the
      criteria for closed, non-penetrating, mild TBI and who present at baseline with moderate to
      severe memory impairment. Memory impairment will be defined as a Total Recall index (Trials
      1-3) of the Hopkins Verbal Learning Test-Revised (HVLT-R) that is at least 25% lower than the
      intelligence-adjusted expected score, as assessed by the Wechsler Adult Intelligence Scale -
      Fourth Edition (WAIS-IV) Information and Vocabulary subtests. The study consists of a
      screening period, one-week single-blind, placebo run-in phase, and a 12-week double-blind
      acute treatment phase (Phase I). Subjects will be randomized 1:1 to rivastigmine transdermal
      patch 9.5mg/24 hours (10cm2) or matching placebo. During Phase I, there will be an initial
      4-week titration period followed by an 8-week continuation phase. Following the 12-week acute
      treatment phase, randomized patients will continue in the double-blind phase (Phase II) for
      additional 14 weeks or until study treatment period ends. Recruitment stage ended 2.25.16.
      Efficacy will be determined by comparing the proportion of patients in each treatment group
      who are classified as responders at week 12. Secondary measure of functional capacity
      assessing the impact of memory improvement on real-world functioning, other measures of
      cognitive domains affected in TBI, namely attention, working and episodic memory and
      executive functions, as well as measures of mood and quality of life will be examined. Study
      findings will contribute to the body of evidence needed to establish standards of care for
      Veterans with posttraumatic memory impairment and other cognitive deficits.
    

Intervention name(s): Rivastigmine Transdermal Patch
Intervention type(s): Drug
Intervention description(s): Cholinesterase Inhibitor
Other intervention name(s): Cholinesterase Inhibitor
Intervention MeSH terms: Rivastigmine; Cholinesterase Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Traumatic Brain Injury; Cognitive Impairment; Rivastigmine; Pharmacologic Actions; TBI; Memory; Cholinesterase Inhibitors; Cognition; Head Trauma