Improving Stroke Rehabilitation: Spacing Effect and D-cycloserine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00720759
First received: July 21, 2008
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Stroke
Drug: D-cycloserine + distributed treatment
Behavioral: D-cycloserine + condensed treatment
Drug: Placebo + distributed treatment
Behavioral: Placebo + condensed treatment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Improving Stroke Rehabilitation: Spacing Effect and D-cycloserine

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Wolf Motor Function Test (Time) [ Time Frame: 3 months after completion of treatment ] [ Designated as safety issue: No ]
    The Wolf Motor Function Test (time) score is the average time in seconds taken to perform each of 15 functional tasks ranging in difficulty from putting one's forearm on a table to stacking checkers. Participants are given 120 seconds to perform a task and if they fail, they are scored 120 for that task. Score range on the WMFT-T is 0-120, lower scores being better.


Enrollment: 24
Study Start Date: July 2009
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
D-cycloserine + distributed treatment
Drug: D-cycloserine + distributed treatment
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
Other Name: spaced training
Sham Comparator: Arm 2
D-cycloserine + condensed treatment
Behavioral: D-cycloserine + condensed treatment
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
Placebo Comparator: Arm 3
Placebo + distributed treatment
Drug: Placebo + distributed treatment
Subjects will receive CIMT 2 hours/day, 3 days a week, for 10 weeks, in conjunction with placebo administered before each treatment session
Other Name: spaced training
Placebo Comparator: Arm 4
Placebo + condensed treatment
Behavioral: Placebo + condensed treatment
Subjects will receive CIMT 6 hours/day, 5 days a week, for 2 weeks, in conjunction with placebo administered before each treatment session

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.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 21-80,
  • of either sex,
  • diverse ethnic background,
  • s/p a single unilateral hemispheric stroke 6 or more months prior,
  • who meet upper extremity functional criteria for participation in constraint induced movement therapy.

Exclusion Criteria:

  • History of more than minor head trauma,
  • subarachnoid hemorrhage,
  • dementia or other neurodegenerative disease,
  • multiple sclerosis,
  • lobar intracerebral hemorrhage,
  • epilepsy,
  • drug or alcohol abuse,
  • serious medical illness,
  • serum creatinine >1.5,
  • schizophrenia,
  • major refractory depression,
  • insufficient cardiopulmonary function to participate in low-intensity,
  • sustained upper extremity exercise,
  • severe visual impairment,
  • pregnancy,
  • inability to understand the potential risks and benefits of the study,
  • personally provide informed consent, and
  • understand and cooperate with treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720759

Locations
United States, Florida
North Florida/South Georgia Veterans Health System, Gainesville, FL
Gainesville, Florida, United States, 32608
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen E Nadeau, MD BS BS North Florida/South Georgia Veterans Health System, Gainesville, FL
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00720759     History of Changes
Other Study ID Numbers: B6346-R
Study First Received: July 21, 2008
Results First Received: October 7, 2013
Last Updated: January 21, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
stroke
hemiparesis
randomized controlled trial
d-cycloserine
distributed practice
constraint induced movement therapy

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014