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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01963832
Recruitment Status : Withdrawn (not funded)
First Posted : October 16, 2013
Last Update Posted : January 12, 2015
Information provided by (Responsible Party):
University of Alabama at Birmingham

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Severe Stroke With Affected Arm Motor Function Drug: Fluoxetine Drug: Placebo Procedure: eCMIT Procedure: Usual Care Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: RCT of a Neuroplasticity Agent and CI Therapy for Severe Arm Paresis After Stroke
Study Start Date : November 2016
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Fluoxetine

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: Fluoxetine
Drug: Placebo
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

Primary Outcome Measures :
  1. Grade 4/5 Motor Activity Log (MAL) Arm Use Scale [ Time Frame: baseline to 90 days ]
    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.

Secondary Outcome Measures :
  1. Grade 4/5 MAL Arm Use scale [ Time Frame: baseline to 12 months after therapy ]
    See primary outcome.

  2. Grade 4/5 Wolf Motor Function Test Performance Rate score [ Time Frame: baseline to 90 days ]
    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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01963832

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Sponsors and Collaborators
University of Alabama at Birmingham

Responsible Party: University of Alabama at Birmingham Identifier: NCT01963832     History of Changes
Other Study ID Numbers: F130410007
First Posted: October 16, 2013    Key Record Dates
Last Update Posted: January 12, 2015
Last Verified: December 2014

Keywords provided by University of Alabama at Birmingham:
Fluoxetine (FLX)
Central Nervous System

Additional relevant MeSH terms:
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Neurologic Manifestations
Signs and Symptoms
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors