Improving Stroke Rehabilitation: Spacing Effect and D-cycloserine

• ClinicalTrials.gov Identifier: NCT00720759
• Recruitment Status: Completed
• First Posted: July 23, 2008
• Results First Posted: March 7, 2014
• Last Update Posted: March 7, 2014
• Sponsor: US Department of Veterans Affairs
• Information provided by (Responsible Party): VA Office of Research and Development ( US Department of Veterans Affairs )

Study Description

Brief 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.

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

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Improving Stroke Rehabilitation: Spacing Effect and D-cycloserine
• Study Start Date: July 2009
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Wolf Motor Function Test (Time) [ Time Frame: 3 months after completion of treatment ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Florida

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, United States, 32608

Sponsors and Collaborators

US Department of Veterans Affairs

Investigators

• Principal Investigator: Stephen E Nadeau, MD BS BS; North Florida/South Georgia Veterans Health System, Gainesville, FL

More Information

• Responsible Party: US Department of Veterans Affairs
• ClinicalTrials.gov Identifier: NCT00720759
• Other Study ID Numbers: B6346-R
• First Posted: July 23, 2008
• Results First Posted: March 7, 2014
• Last Update Posted: March 7, 2014
• Last Verified: January 2014

Keywords provided by VA Office of Research and Development ( US Department of Veterans Affairs ):

stroke; hemiparesis; randomized controlled trial; d-cycloserine; distributed practice; constraint induced movement therapy

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cycloserine; Anti-Infective Agents, Urinary; Anti-Infective Agents; Renal Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action