RCT of a Neuroplasticity Agent and CI Therapy for Severe Arm Paresis After Stroke

Stroke patients who have little or no voluntary movement in the hand on the more affected side of their body more than one year after stroke have few treatment options. This project proposes to test the efficacy of a form of Constraint-Induced Movement therapy designed for patients with such severe impairment in conjunction with an agent, fluoxetine, which has been shown in some studies to enhance brain neuroplasticity in response to training. Constraint-Induced Movement therapy, which is abbreviated CIMT, is a form of physical rehabilitation based on basic research in neuroscience and behavioral science. If the project is successful, an efficacious, evidence-based therapy will become available to stroke patients for what is now a largely untreated condition

Study Overview

• Status: Withdrawn
• Conditions: Severe Stroke With Affected Arm Motor Function
• Intervention / Treatment: Drug: Placebo; Drug: Fluoxetine; Procedure: eCMIT; Procedure: Usual Care

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Motor criteria determinations will be made with the subject sitting. The more-affected forearm will be resting on a supporting surface (e.g., arm of a chair) to allow for maximum wrist flexion with gravity.

• The minimum motor criterion (MMC) for inclusion in Grade 5 (severe impairment) will be ability to:

  • initiate extension against gravity at the wrist or at least one digit,
  • initiate extension and flexion at the elbow,
  • actively move the shoulder ≥ 30° in flexion, abduction, or scaption

• The MMC for inclusion in Grade 4 (moderately severe impairment) will be ability to actively:

  • extend at least two fingers more than 0° but less than < 10°,
  • extend or abduct thumb ≥ 10°
  • extend wrist ≥ 10° from a fully flexed starting position,
  • extend elbow ≥ 20° from a 90° flexed starting position,
  • flex and abduct shoulder > 45°.
• Stroke patients who can extend at least two fingers ≥ 10° at the metacarpophalangeal (MCP) joint and either the proximal or distal interphalangeal (PIP or DIP) joint will be excluded.

• Additional inclusion criteria are:

  • must score ≤ 4 on the Modified Ashworth Scale (23)116 for all more-affected arm joints

  • meet the following passive range of movement criteria:

    • ≥ 90° shoulder flexion,
    • ≥ 90° shoulder abduction,
    • ≥ 45° shoulder external rotation,
    • ≤ 30° short of normal elbow extension, forearm supination to at least neutral,
    • forearm pronation 45° or more from neutral,
    • ≤ 35° short of normal wrist extension,
    • ≤ 35° short of normal MCP extension on all the digits.

Exclusion Criteria:

• Less than 1 year post-stroke.
• Frailty or insufficient stamina to carry out the requirements of the therapy (based on clinical judgment).
• Ferrous metal in body or medical complications or psychological problems that would prohibit receiving an MRI.
• Positive pregnancy test for women of child-bearing age since 3T MRI is contraindicated for pregnant women.
• Other neurological or musculoskeletal conditions affecting UE function.
• Medication will not be exclusionary except in the following cases: a. participation in any experimental drug study, b. Botox injections to the more-affected UE < 3 months prior to enrollment, c. Baclofen or Dantrium taken orally at the time of study, d. fluoxetine or other antidepressant with SSRI-like properties taken < 3 months prior to enrollment, e. any agents that would contraindicate concurrent fluoxetine. If subjects are on other medications, the medications will be recorded and the possible effect on treatment outcome will be analyzed separately.
• Moderate or greater depressive symptoms as indicated by a score > 30/63 on the Beck Depression Inventory (24,25).117, 118
• Concurrent participation in any formal physical rehabilitation program or clinical trial.
• Excessive pain in any joint of the more-affected arm that could limit ability to cooperate with the intervention (based on clinical judgment).
• Serious cognitive deficits manifested by a Folstein Mini-Mental State Examination (MMSE) score ≤ 24 (26).119
• Inadequate ability to follow test instructions as indicated by a Token Test of the Multilingual Aphasia Examination score ≤ 36 (27).120
• Serious, uncontrolled medical problems as judged by the Medical Director (e.g., severe rheumatoid arthritis, serious joint deformity of arthritic origin, symptomatic cancer or renal disease, any end-stage pulmonary or cardiovascular disease, senility or a deteriorated condition due to age, uncontrolled epilepsy).
• Motor problems that are not primarily unilateral.
• Poor motivation to participate in the study (if a person is only marginally interested, he/she is a bad risk as a subject).
• Less than 40 years old.
• Previous CIMT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eCMIT and Fluoxetine; expanded form of Constraint Induced Movement Therapy (eCIMT) combined with Fluoxetine (FLX)	Drug: Fluoxetine; Procedure: eCMIT
Experimental: eCIMT and placebo; expanded form of Constraint Induced Movement Therapy (eCIMT) combined with placebo	Drug: Placebo; Drug: Fluoxetine
Experimental: Usual care and fluoxetine; Ususal physical care combined with Fluoxetine (FLX)	Drug: Fluoxetine; Procedure: Usual Care
Experimental: Usual care and placebo; Usual physical care combined with placebo	Drug: Placebo; Procedure: Usual Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 4/5 Motor Activity Log (MAL) Arm Use Scale	This is a structured interview. Patients and family caregivers, if available, are asked to rate how well and how much the stroke survivor has used his or her more-affected arm on 30 upper-extremity tasks outside of the treatment setting over a specified period. The test score is the mean of the item scores. The primary outcome will be change on this instrument from pre- to post-treatment.	baseline to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 4/5 MAL Arm Use scale	See primary outcome.	baseline to 12 months after therapy
Grade 4/5 Wolf Motor Function Test Performance Rate score	This is a laboratory motor performance test. Patients are asked to complete the items are rapidly as possible. Performance is timed and converted to a rate (repetitions/60 s). The test score is the mean of the item scores.	baseline to 90 days

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: October 11, 2013
• First Submitted That Met QC Criteria: October 15, 2013
• First Posted (Estimate): October 16, 2013

Study Record Updates

• Last Update Posted (Estimate): January 12, 2015
• Last Update Submitted That Met QC Criteria: January 9, 2015
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: stroke; Central Nervous System; Fluoxetine (FLX); eCIMT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Stroke; Paresis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: F130410007