Amphetamine-Enhanced Stroke Recovery

Completed

Phase 2 Results N/A

Trial Description

This is an NIH Pilot Clinical Trial Grant designed to provide data to permit the rationale design of a subsequent efficacy study. The purpose of this project is to determine the potential benefit of amphetamine combined with physical therapy in enhancing motor recovery in patients admitted for inpatient rehabilitation between 10 and 30 days after hemispheric ischemic stroke. The study hypotheses are: 1, The addition of treatment with d-amphetamine will result in at least a 12.6 point improvement in the Fugl-Meyer motor score 3 months after stroke. 2, There will be no clinically significant increase in the frequency of serious adverse events associated with treatment with d-amphetamine which would preclude further testing.

Detailed Description

The purpose of this Pilot Grant is to collect data critical for the design of a subsequent full-scale clinical trial testing the efficacy of treatment with amphetamine combined with physical therapy to facilitate poststroke motor recovery. When combined with task-relevant experience, a single dose of d amphetamine given 24 hr following a unilateral sensorimotor cortex ablation in the rat results in an enduring enhancement of motor recovery. This amphetamine effect extends to functional deficits that occur following focal lesions produced through a variety of mechanisms including ischemic brain injury, to lesions affecting other areas of the cortex, and to other behaviors. Laboratory studies not only show that certain drugs such as amphetamine may facilitate recovery, but that other classes of drugs may be harmful. Clinical studies suggest similar detrimental drug effects may occur in humans recovering from stroke. Three small studies of the impact of treatment with amphetamine on poststroke recovery have been carried out. Two found a beneficial effect and the third was negative. These studies differed in significant ways as reviewed in the referenced section of the proposal. The present study is designed based on these small studies. Using a multicenter, block-randomized, placebo-controlled design, this pilot study will:
1. Refine the intervention strategy which has been developed for this Pilot Grant based on the best available laboratory and preliminary clinical data.
2. Refine the target patient population.
3. Gain information to permit an accurate sample size calculation (estimated for this pilot study) for a subsequent trial.
4. Refine outcome measures, site monitoring techniques, data consistency protocols, and data management procedures.
5. Obtain data to further support the safety of the proposed intervention.
This study has several hypotheses.
1. Patients treated with d-amphetamine combined with physical therapy will have improved recovery of motor function as compared to similar patients treated with placebo combined with physical therapy measured 90 days after hemispheric ischemic stroke.
2. There will not be a clinically significant increase in the frequency of serious adverse events associated with treatment with d-amphetamine which would preclude further testing of these regimens.
Secondary goals include:
1. Refinement of the target patient population.
2. Gain information to permit an accurate sample size calculation (estimated for this pilot study) for a subsequent trial.
3. Refinement of outcome measures, site monitoring techniques, data consistency protocols, and data management procedures.

Conditions

Interventions

  • Physical therapy Other
    Intervention Desc: One hour of active physical therapy (PT) directed at a primary motor impairment. An outline indicating a range and level of physical therapy interventions will be provided to the therapists, and the level and of therapy will be recorded.
    ARM 1: Kind: Experimental
    Label: Dextroamphetamine + Physical therapy (PT)
    Description: Treatment with d-amphetamine + physical therapy administered under two regimens administered sequentially: 10 mg of d-amphetamine combined with 1 hr PT session beginning 1 hr after drug administration every 4 days, for a total of 6 or 10 sessions
    ARM 2: Kind: Experimental
    Label: Placebo + Physical Therapy (PT)
    Description: Treatment with placebo + physical therapy administered under two regimens administered sequentially: Regimen 1: 10 mg of placebo combined with 1 hr PT session beginning 1 hr after placebo administration every 4 days, for a total of 6 or 10 sessions
  • Placebo Drug
    ARM 1: Kind: Experimental
    Label: Placebo + Physical Therapy (PT)
    Description: Treatment with placebo + physical therapy administered under two regimens administered sequentially: Regimen 1: 10 mg of placebo combined with 1 hr PT session beginning 1 hr after placebo administration every 4 days, for a total of 6 or 10 sessions
  • Dextroamphetamine Drug
    Other Names: D-amphetamine
    ARM 1: Kind: Experimental
    Label: Dextroamphetamine + Physical therapy (PT)
    Description: Treatment with d-amphetamine + physical therapy administered under two regimens administered sequentially: 10 mg of d-amphetamine combined with 1 hr PT session beginning 1 hr after drug administration every 4 days, for a total of 6 or 10 sessions

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Mean Change in Fugl-Meyer Score from Baseline to 90 days Poststroke 90 days, Baseline No
Secondary Mean Change in Ambulation Speed Score from Baseline to 90 Days Poststroke 90 days, Baseline No
Secondary Mean Change in Ambulation Endurance Score from Baseline to 90 days Poststroke 90 days, Baseline No
Secondary Mean Change in the Action Research Arm Test (ARAT) score from Baseline to 90 days Poststroke 90 days, Baseline No
Secondary Mean Change in the Mobility Subscale of the Functional Independence Measure from Baseline 90 days, Baseline No
Secondary Mean Change in the NIH Stroke Scale Score from Baseline 90 days, Baseline No
Secondary Mean Change in Rankin Scale Score from Baseline 90 days, Baseline No
Secondary Mean Change in Mini-Mental State Examination Score 90 days, Baseline No

Sponsors