Stroke With Hemiparesis
Conditions
Keywords
Rehabilitation, Fingers, Grasp, Hand, Strength, Brain Infraction, Pathology, Physiopathology, Functional Laterality, Neuronal Plasticity, Psychomotor Performance, Biomechanics, Touch, Weight-Bearing
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).
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.
Interventions
DRUGBotulinum 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.
DRUGPlacebo
The control group will receive a placebo injection.
Sponsors
Allergan
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Taken to Form a Stable Grasp Pre-Treatment | 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. |
| Time Taken to Form a Stable Grasp Post Treatment | 90 Days | * Hand motor impairment (execution and planning) during a functional grasp and lift tasks. * Hand function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Upper Limb Motor Impairment Measured by Fugl Meyer Scale | 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) |
| Disability Measured by Modified Rankin Scale Score Post-Treatment | 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). |
| Motor Impairment Measured by the Fugl-Meyer Scale Post-Treatment | 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). |
| Disability Measured by Modified Rankin Scale Score Pre-Treatment | 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). |
Countries
United States
Participant flow
Recruitment details
Sample size is estimated based on a treatment difference of 20% between the two groups
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin Commonly Known as BOTOX® Some subjects will receive BOTOX® injections. Subject will not be informed of what injection they received.
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.
The control group will receive a placebo injection. There will be 1 treatment cycle during the 9 week study. | 10 |
| Placebo Some subject will receive a safe Placebo injection. Subjects will not be informed of what injection they have received.
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.
The control group will receive a placebo injection. There will be 1 treatment cycle during the 9 week study. | 6 |
| Total | 16 |
Baseline characteristics
| Characteristic | Botulinum Toxin Commonly Known as BOTOX® | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 6 Participants | 16 Participants |
| Region of Enrollment United States | 10 participants | 6 participants | 16 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 |
| other Total, other adverse events | 0 / 10 | 0 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 |
Outcome results
Primary
Time Taken to Form a Stable Grasp Post Treatment
* Hand motor impairment (execution and planning) during a functional grasp and lift tasks. * Hand function.
Time frame: 90 Days
Population: Time taken to form a stable grasp.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control (Saline) Group -PRE Treatment | Time Taken to Form a Stable Grasp Post Treatment | 2.65 Preload phase duration in Seconds | Standard Error 0.17 |
| Botox Group -PRE Treatment | Time Taken to Form a Stable Grasp Post Treatment | .79 Preload phase duration in Seconds | Standard Error 0.09 |
Primary
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.
Time frame: Day 1
Population: Improved motor execution as measured by the time taken to form a stable grasp.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control (Saline) Group -PRE Treatment | Time Taken to Form a Stable Grasp Pre-Treatment | 1.51 Preload phase duration in Seconds | Standard Error 0.21 |
| Botox Group -PRE Treatment | Time Taken to Form a Stable Grasp Pre-Treatment | 1.14 Preload phase duration in Seconds | Standard Error 0.59 |
Secondary
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).
Time frame: 90 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control (Saline) Group -PRE Treatment | Disability Measured by Modified Rankin Scale Score Post-Treatment | 2 Modified Rankin Scale Score | Standard Deviation 0.36 |
| Botox Group -PRE Treatment | Disability Measured by Modified Rankin Scale Score Post-Treatment | 1.8 Modified Rankin Scale Score | Standard Deviation 0.24 |
Secondary
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).
Time frame: Pre-Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control (Saline) Group -PRE Treatment | Disability Measured by Modified Rankin Scale Score Pre-Treatment | 2.3 Modified Rankin Scale Score | Standard Deviation 0.33 |
| Botox Group -PRE Treatment | Disability Measured by Modified Rankin Scale Score Pre-Treatment | 2.6 Modified Rankin Scale Score | Standard Deviation 0.33 |
Secondary
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)
Time frame: Pre-Treatment, Day 90
Population: Total upper limb Fugl Meyer scale score out of 66.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control (Saline) Group -PRE Treatment | Measure of Upper Limb Motor Impairment Measured by Fugl Meyer Scale | 47.6 Fugl Meyer Scale Score | Standard Error 4 |
| Botox Group -PRE Treatment | Measure of Upper Limb Motor Impairment Measured by Fugl Meyer Scale | 40.7 Fugl Meyer Scale Score | Standard Error 3.31 |
Secondary
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).
Time frame: 1 Day and 90 Days
Population: Total upper limb Fugl Meyer Score out of 66.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control (Saline) Group -PRE Treatment | Motor Impairment Measured by the Fugl-Meyer Scale Post-Treatment | 52.1 score on a scale | Standard Error 3.5 |
| Botox Group -PRE Treatment | Motor Impairment Measured by the Fugl-Meyer Scale Post-Treatment | 45.5 score on a scale | Standard Error 2.85 |