Study of Botulinum Toxin and Recovery of Hand Function After Stroke

• ClinicalTrials.gov Identifier: NCT01422161
• Recruitment Status: Completed
• First Posted: August 23, 2011
• Results First Posted: May 31, 2019
• Last Update Posted: June 20, 2019
• Sponsor: NYU Langone Health
• Collaborator: Allergan
• Information provided by (Responsible Party): NYU Langone Health

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Stroke With Hemiparesis	Drug: Botulinum Toxin commonly known as BOTOX®; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Botulinum Toxin Type A Therapy as a Plasticity Inducing Agent for Recovery of Hand Function After Stroke
• Study Start Date: April 2010
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: October 2015

Arms and Interventions

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: BOTOX®; Saline
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.

Outcome Measures

Primary Outcome Measures :

1. Time Taken to Form a Stable Grasp Pre-Treatment [ Time Frame: Day 1 ]

   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.
2. Time Taken to Form a Stable Grasp Post Treatment [ Time Frame: 90 Days ]
   • Hand motor impairment (execution and planning) during a functional grasp and lift tasks.
   • Hand function.

Secondary Outcome Measures :

1. Measure of Upper Limb Motor Impairment Measured by Fugl Meyer Scale [ Time Frame: Pre-Treatment, Day 90 ]

   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)

2. Disability Measured by Modified Rankin Scale Score Post-Treatment [ Time Frame: 90 Days ]
   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).
3. Motor Impairment Measured by the Fugl-Meyer Scale Post-Treatment [ Time Frame: 1 Day and 90 Days ]
   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).
4. Disability Measured by Modified Rankin Scale Score Pre-Treatment [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, New York

New York University School of Medicine

New York, New York, United States, 10016

Sponsors and Collaborators

NYU Langone Health

Allergan

Investigators

• Principal Investigator: Preeti Raghavan, MD; NYU Langone Health

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT01422161
• Other Study ID Numbers: 10-01126; 10-01126 ( Other Identifier: Institutional Review Board (IRB) - NYU School of Medicine )
• First Posted: August 23, 2011
• Results First Posted: May 31, 2019
• Last Update Posted: June 20, 2019
• Last Verified: June 2019

• 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

Keywords provided by NYU Langone Health:

Rehabilitation; Fingers; Grasp; Hand; Strength; Brain Infraction; Pathology; Physiopathology; Functional Laterality; Neuronal Plasticity; Psychomotor Performance; Biomechanics; Touch; Weight-Bearing

Additional relevant MeSH terms:

Stroke; Paresis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Botulinum Toxins; Botulinum Toxins, Type A; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents