Study of Botulinum Toxin and Recovery of Hand Function After Stroke

Botulinum Toxin Type A Therapy as a Plasticity Inducing Agent for Recovery of Hand Function After Stroke

The purpose of this study is to determine whether injections of botulinum toxin (commonly known as BOTOX®) into the affected hand of Stroke patients, while targeting the muscles controlling the hand, will lead to improved use of the hand when compared to injections of placebo (a substance that looks similar to the study drug but contains no active study medication).

Study Overview

• Status: Completed
• Conditions: Stroke With Hemiparesis
• Intervention / Treatment: Drug: Botulinum Toxin commonly known as BOTOX®; Drug: Placebo

Detailed Description

Hemiparesis is the most common motor impairment after stroke that frequently leads to persistent deficits in hand function. This study investigates whether the application of botulinum toxin to a set of synergistically-acting hand muscles, in conjunction with task-specific therapy, will lead to reorganization and improved motor function in the stroke-involved hand. The investigators will use objective psychophysical measures of hand function and hand function rating scales to investigate if Botox in conjunction with task-specific therapy will lead to:

• improved motor execution,
• improved motor planning during a psychophysical two-finger grasping and lifting task with varying object weight, and
• increased hand function as assessed by the time taken to complete fine motor tasks.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to follow study instructions and likely to complete all required visits
• Ability to comply with the therapy protocol as assessed by the investigator
• 3 months post first-time unilateral stroke with right or left hemiparesis and complaints of unilateral hand dysfunction
• Must have ability to grasp and lift the test object
• Subjects must have upper extremity motor impairment

Exclusion Criteria:

• Known allergy or sensitivity to botulinum toxin type A (BOTOX).
• Females with a positive pregnancy test, or who are breast-feeding, planning a pregnancy during the study, who think that they may be pregnant at the start of the study or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study.
• Concurrent participation in another investigational drug or device study or participation in another Botulinum toxin study in the 6 months prior to study.
• Treatment with botulinum toxin of any serotype in the 3 months prior to study enrollment
• Any medical condition that may put the subject at increased risk with exposure to BOTOX including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amytrophic lateral sclerosis, or any other disorder that might interfere with neuromuscular function.
• Evidence of alcohol, drug abuse or other relevant neuropsychiatric condition.
• Infection or skin disorder at an anticipated injection site.
• Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
• History of surgery or other significant injury to either upper extremity causing mechanical limitations that preclude task performance.
• Previous neurological illness such as head trauma, prior stroke, epilepsy, or demyelinating disease.
• Complicating medical problems such as uncontrolled hypertension, diabetes with signs of polyneuropathy, severe renal, cardiac or pulmonary disease, or evidence of other concurrent neurologic or orthopedic conditions precluding the subject from complying with the study protocol.
• Current treatment with intrathecal baclofen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Botulinum Toxin commonly known as BOTOX®; Some subjects will receive BOTOX® injections. Subject will not be informed of what injection they received.	Drug: Botulinum Toxin commonly known as BOTOX®; A total dose between 200-300 units of Botulinum toxin will be administered across 12 muscles of the affected hand. There will be 1 treatment cycle during the 9 week study.; Other Names: Saline; BOTOX®
PLACEBO_COMPARATOR: Placebo; Some subject will receive a safe Placebo injection. Subjects will not be informed of what injection they have received.	Drug: Placebo; The control group will receive a placebo injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Taken to Form a Stable Grasp Pre-Treatment	Assessments are done on day 1, before the 1st Botulinum toxin injection. They will be assessed for: Hand motor impairment (execution and planning) during a functional grasp and lift tasks.; Hand function.	Day 1
Time Taken to Form a Stable Grasp Post Treatment	Hand motor impairment (execution and planning) during a functional grasp and lift tasks.; Hand function.	90 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Upper Limb Motor Impairment Measured by Fugl Meyer Scale	This scale has 3 points for each item. A zero is given for the item if the subject cannot do the task. A score of 1 is given when the task is performed partially and a score of 2 is given when the task is performed fully. Reflex activity is measured using 2 points only, with a score of 0 or 3 for absence and presence of reflex. The maximum total score that can be obtained in Fugl Meyer assessment is 226, though it is common practice to assess all domains separately.The five domains assessed by Fugl-Meyer scale are: Motor function (Maximum score in upper limb = 66; Maximum score in lower limb = 34) Sensory function (Maximum score = 24) Balance (Maximum score = 14) Range of motion of joints (Maximum score = 44) Joint pain (Maximum score = 44)	Pre-Treatment, Day 90
Disability Measured by Modified Rankin Scale Score Post-Treatment	Measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.The mRS is an ordered scale coded from 0 (no symptoms at all), 1 (No significant disability despite symptoms; able to carry out all usual duties and activities), 2 (Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance), 3 (Moderate disability; requiring some help, but able to walk without assistance), 4 (Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance), 5 (severe disability) and 6 (death).	90 Days
Motor Impairment Measured by the Fugl-Meyer Scale Post-Treatment	Scale is comprised of five domains and there are 155 items in total: Motor functioning (in the upper and lower extremities); Sensory functioning (evaluates light touch on two surfaces of the arm and leg, and position sense for 8 joints); Balance (contains 7 tests, 3 seated and 4 standing); Joint range of motion (8 joints); Joint pain. Each domain contains multiple items, each scored on a 3-point ordinal scale (0 = cannot perform, 1= perform partially, 2 = perform fully).	1 Day and 90 Days
Disability Measured by Modified Rankin Scale Score Pre-Treatment	Measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.The mRS is an ordered scale coded from 0 (no symptoms at all), 1 (No significant disability despite symptoms; able to carry out all usual duties and activities), 2 (Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance), 3 (Moderate disability; requiring some help, but able to walk without assistance), 4 (Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance), 5 (severe disability) and 6 (death).	Pre-Treatment

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Allergan

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: August 19, 2011
• First Submitted That Met QC Criteria: August 22, 2011
• First Posted (ESTIMATE): August 23, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 20, 2019
• Last Update Submitted That Met QC Criteria: June 4, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Rehabilitation; Biomechanics; Hand; Strength; Pathology; Neuronal Plasticity; Weight-Bearing; Psychomotor Performance; Fingers; Grasp; Brain Infraction; Touch; Physiopathology; Functional Laterality
• 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; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A
• Other Study ID Numbers: 10-01126 (OTHER: Institutional Review Board (IRB) - NYU School of Medicine)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No