Improving Stroke Rehabilitation: Spacing Effect and D-cycloserine
Condition: Stroke
MeSH terms: Stroke
Study type: Interventional
Phase: Phase 2

Summary: 
      Each year 730,000 Americans experience a stroke. Forty percent are left with significant
      paralysis of one arm. Certain types of physical therapy, for example constraint induced
      movement therapy (CIMT), have been shown to be effective in improving arm function. However,
      for most subjects, improvement is modest. In this trial, we test two approaches that may
      increase the amount of improvement achieved: 1) distributing treatment over a greater amount
      of time; and 2) adding a drug, d-cycloserine, which theoretically enhances the molecular
      mechanisms of learning.
    

Detailed description: 
      Each year, 730,000 Americans experience a stroke. Forty percent are left with persistent
      impairment of upper extremity function. Although scientifically vetted rehabilitation
      therapies for this impairment are starting to emerge, current treatment is generally
      unsatisfactory. Therapies that seek to engage neuroplastic mechanisms constitute one approach
      to this problem. A good example is constraint induced movement therapy (CIMT), a treatment
      that seeks, through extensive functional task practice, to overcome an acquired intentional
      predisposition to use the spared arm (learned non-use), and to improve motor function in the
      affected arm. CIMT has been tested in a host of trials, most recently a multicenter
      randomized controlled trial (RCT) - the EXCITE trial. These trials have generally
      demonstrated that on average, the treatment shows efficacy, and the results from the RCT
      indicate that it is more efficacious than "standard" therapies. However, problems with CIMT
      can be readily identified that pose research challenges: 1) on average, efficacy is limited;
      2) only a fraction of subjects show substantial benefit. We propose to address these two
      problems in a pilot RCT of 20 subjects that will test two modifications of standard CIMT: 1)
      addition of a drug, d-cycloserine, that may enhance neuroplasticity by potentiating
      NMDA-glutamate receptor-mediated learning mechanisms; 2) delivery of a fixed amount of CIMT
      over a greater number of days, which according to learning research, may enhance long-term
      retention of gains.

      All subjects in this trial will receive CIMT. Subjects will be randomized to one of 4 groups:

      A. CIMT + d-cycloserine, more condensed treatment B. CIMT + d-cycloserine, less condensed
      treatment C. CIMT + placebo, more condensed treatment D. CIMT + placebo, less condensed
      treatment The primary outcome measure will be performance on the Wolf Motor Function Test
      (time) 3 months after completion of treatment.
    

Intervention name(s): D-cycloserine + distributed treatment; D-cycloserine + condensed treatment; Placebo + distributed treatment; Placebo + condensed treatment
Intervention type(s): Drug; Behavioral; Drug; Behavioral
Intervention description(s): Subjects will receive CIMT 2 hours/day, 3 days a week, for 10 weeks, in conjunction with d-cycloserine 50 mg PO administered before each treatment session; Subjects will receive CIMT 6 hours/day, 5 days a week, for 2 weeks, in conjunction with d-cycloserine 50 mg PO administered before each treatment session; Subjects will receive CIMT 2 hours/day, 3 days a week, for 10 weeks, in conjunction with placebo administered before each treatment session; Subjects will receive CIMT 6 hours/day, 5 days a week, for 2 weeks, in conjunction with placebo administered before each treatment session
Other intervention name(s): spaced training; spaced training
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: stroke; hemiparesis; randomized controlled trial; d-cycloserine; distributed practice; constraint induced movement therapy