BOTOX® Versus Zanaflex® for the Treatment of Post-Stroke or Traumatic Brain Injury Upper Limb Spasticity
Primary Purpose
Upper Limb Spasticity
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
BOTOX®
Zanaflex®
Sponsored by
About this trial
This is an interventional treatment trial for Upper Limb Spasticity
Eligibility Criteria
Inclusion Criteria:
- Outpatient, male and female subjects, of any race, between 18 and 85 years of age.
- Female subjects of childbearing potential must have a negative urine pregnancy test result at Visit 1/Screening. (A female is considered of childbearing potential unless she is postmenopausal or without a uterus and/or both ovaries.)
Subjects with a history of stroke or traumatic brain injury, more than 90 days prior to Visit 2/Baseline, that result in disability caused by focal upper limb muscle over activity, as assessed by the Investigator and characterized by the following:
- A wrist Ashworth tone of +3 or greater as measured on the Modified Ashworth Scale at Visit 1/Screening and Visit 2/Baseline;
- A minimum measurement of +2 on the Disability Assessment Scale (DAS) for the principal therapeutic intervention target assessment (hygiene, dressing, pain, and cosmesis) chosen by the Investigator and the subject or subject's caregiver at Visit 1/Screening and Visit 2/baseline.
- Subjects, who, as assessed by the Investigator, clearly understand the intent of the study and are willing and able to comply with study instructions, complete the entire study and sign Informed Consent Form.
Exclusion Criteria:
- Female subjects who are pregnant (positive urine pregnancy test at Visit 1/screening), nursing, planning a pregnancy during the study period or female subjects of childbearing potential who are not using a reliable means of contraception. Reliable means of contraception. Reliable methods of contraception are hormonal methods or intrauterine device in use at least 14 days before study drug administration.
- Subjects with a severe contracture at the wrist (inability to passively move the joint more than 10 degrees) or a history of tendon transfer in the study limb.
- Subjects who have had a cast of the study limb within two weeks of the Visit 1/Screening or are planning casting of the study limb during the study period.
- Subjects with a diagnosis of Myasthenia Gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis or any other disease that might interfere with neuromuscular function.
- Subjects with profound atrophy (as per the Investigator's assessment) of the muscle in the target area(s) of injection.
- Subjects with an infection at the injection site or systemic infection (in this case, postpone study entry until one week following recovery).
- Subjects with diagnosed orthostatic hypotension or subjects that are taking alpha-2 adrenergic agonists (e.g. clonidine).
- Subjects with impaired renal and/or hepatic function.
- Subjects with a known allergy or sensitivity to the study medications or its components.
- Subjects who are currently taking tizanidine or have taken tizandidine within 14 days prior to Visit 2/Baseline.
- Subjects who have received previous botulinum toxin injection(s) of any serotype into the target limb within 4 months of Visit 2/Baseline.
- Subjects who have received phenol or alcohol injections to the study limb.
- Subjects who are currently taking oral gabaergic medications (baclofen, gabapentin, benzodiazepines) or dantrolone sodium, or have been taking these drugs within 2 weeks of baseline (Visit 2). Please note that benzodiazepines will be excluded only as antispasmodic medications but not as hypnotics or anxiolytics on a PRN basis.
- Subjects who have not been on stable doses of their CNS medications (antidepressant, antianxiety drugs) for at least 2 months prior to Visit 1 (dose regimen must remain stable throughout the study).
- Subjects who are currently using medication that are contraindicated with the concomitant use of BOTOX® or Zanaflex®.
- Subjects currently participating in an investigational drug study or who have participated in an investigational drug study within 30 days of Visit 1/Screening.
- Subjects that in the Investigator's opinion have a concurrent condition that may put them at significant risk, may confound the study results, or may interfere significantly with the conduct of the study.
- Subjects with a history of poor cooperation, non-compliance with medical treatment, or unreliability.
- Subjects currently receiving anticoagulant therapy and who have an INR > 3.5
Sites / Locations
Outcomes
Primary Outcome Measures
wrist Modified Ashworth Score
Secondary Outcome Measures
Disability Assessment Scale
Modified Frenchay Assessment
Walking Speed
Contralateral Grip Strength
Contralateral Finger Tap
Epworth Sleepiness Scale
Cognitive Evaluations Questionnaire
Discontinuation
Titration schedule of oral study medication between treatment groups
Full Information
NCT ID
NCT00430196
First Posted
January 30, 2007
Last Updated
January 31, 2007
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
Allergan
1. Study Identification
Unique Protocol Identification Number
NCT00430196
Brief Title
BOTOX® Versus Zanaflex® for the Treatment of Post-Stroke or Traumatic Brain Injury Upper Limb Spasticity
Official Title
Placebo-Controlled Trial of BOTOX® Versus Zanaflex® for the Treatment of Subjects With Post Stroke Upper Limb Spasticity
Study Type
Interventional
2. Study Status
Record Verification Date
January 2007
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
September 2006 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
Allergan
4. Oversight
5. Study Description
Brief Summary
In this study, we will compare BOTOX® versus Zanaflex ® for the treatment of muscle overactivity in the upper limb following stroke or brain traums. This is a critical step in the development of local intramuscular treatment for patients with muscle overactivity following an acute brain lesions, as opposed to the more classic oral treatments.
This study will be a multicenter, randomized, prospective, parallel, double blind study that enrolls subjects at twelve sites (including Mt. Sinai) throughout the United States and Europe. The purpose of this study is to evaluate the safety and efficacy of BOTOX® compared to Zanaflex® in reducing upper limb muscle tone in post-stroke subjects, as well as evaluating changes in muscle tone-related disability and drug-therapy tolerance. This will be an 18 week study. Subjects are eligible if they have been medically stable with upper limb spasticity 6 months after their first stroke. Subjects will be randomized to one of three treatment groups: Treatment Group I - intramuscular BOTOX® plus oral placebo, Treatment Group II - intramuscular placebo plus oral Zanaflex®, Treatment Group III - intramuscular placebo plus oral placebo. The dose of BOTOX® will be at the discretion of the investigator with a maximum of 500 U per subject. The dose of the Zanaflex® will be 4mg/day to a maximum of 36mg/day. The study anticipates that 150 subjects will be enrolled to provide sufficient information to answer the primary objective of safety and efficacy of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Upper Limb Spasticity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
135 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
BOTOX®
Intervention Type
Drug
Intervention Name(s)
Zanaflex®
Primary Outcome Measure Information:
Title
wrist Modified Ashworth Score
Secondary Outcome Measure Information:
Title
Disability Assessment Scale
Title
Modified Frenchay Assessment
Title
Walking Speed
Title
Contralateral Grip Strength
Title
Contralateral Finger Tap
Title
Epworth Sleepiness Scale
Title
Cognitive Evaluations Questionnaire
Title
Discontinuation
Title
Titration schedule of oral study medication between treatment groups
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Outpatient, male and female subjects, of any race, between 18 and 85 years of age.
Female subjects of childbearing potential must have a negative urine pregnancy test result at Visit 1/Screening. (A female is considered of childbearing potential unless she is postmenopausal or without a uterus and/or both ovaries.)
Subjects with a history of stroke or traumatic brain injury, more than 90 days prior to Visit 2/Baseline, that result in disability caused by focal upper limb muscle over activity, as assessed by the Investigator and characterized by the following:
A wrist Ashworth tone of +3 or greater as measured on the Modified Ashworth Scale at Visit 1/Screening and Visit 2/Baseline;
A minimum measurement of +2 on the Disability Assessment Scale (DAS) for the principal therapeutic intervention target assessment (hygiene, dressing, pain, and cosmesis) chosen by the Investigator and the subject or subject's caregiver at Visit 1/Screening and Visit 2/baseline.
Subjects, who, as assessed by the Investigator, clearly understand the intent of the study and are willing and able to comply with study instructions, complete the entire study and sign Informed Consent Form.
Exclusion Criteria:
Female subjects who are pregnant (positive urine pregnancy test at Visit 1/screening), nursing, planning a pregnancy during the study period or female subjects of childbearing potential who are not using a reliable means of contraception. Reliable means of contraception. Reliable methods of contraception are hormonal methods or intrauterine device in use at least 14 days before study drug administration.
Subjects with a severe contracture at the wrist (inability to passively move the joint more than 10 degrees) or a history of tendon transfer in the study limb.
Subjects who have had a cast of the study limb within two weeks of the Visit 1/Screening or are planning casting of the study limb during the study period.
Subjects with a diagnosis of Myasthenia Gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis or any other disease that might interfere with neuromuscular function.
Subjects with profound atrophy (as per the Investigator's assessment) of the muscle in the target area(s) of injection.
Subjects with an infection at the injection site or systemic infection (in this case, postpone study entry until one week following recovery).
Subjects with diagnosed orthostatic hypotension or subjects that are taking alpha-2 adrenergic agonists (e.g. clonidine).
Subjects with impaired renal and/or hepatic function.
Subjects with a known allergy or sensitivity to the study medications or its components.
Subjects who are currently taking tizanidine or have taken tizandidine within 14 days prior to Visit 2/Baseline.
Subjects who have received previous botulinum toxin injection(s) of any serotype into the target limb within 4 months of Visit 2/Baseline.
Subjects who have received phenol or alcohol injections to the study limb.
Subjects who are currently taking oral gabaergic medications (baclofen, gabapentin, benzodiazepines) or dantrolone sodium, or have been taking these drugs within 2 weeks of baseline (Visit 2). Please note that benzodiazepines will be excluded only as antispasmodic medications but not as hypnotics or anxiolytics on a PRN basis.
Subjects who have not been on stable doses of their CNS medications (antidepressant, antianxiety drugs) for at least 2 months prior to Visit 1 (dose regimen must remain stable throughout the study).
Subjects who are currently using medication that are contraindicated with the concomitant use of BOTOX® or Zanaflex®.
Subjects currently participating in an investigational drug study or who have participated in an investigational drug study within 30 days of Visit 1/Screening.
Subjects that in the Investigator's opinion have a concurrent condition that may put them at significant risk, may confound the study results, or may interfere significantly with the conduct of the study.
Subjects with a history of poor cooperation, non-compliance with medical treatment, or unreliability.
Subjects currently receiving anticoagulant therapy and who have an INR > 3.5
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Simpson, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
18977811
Citation
Simpson DM, Gracies JM, Yablon SA, Barbano R, Brashear A; BoNT/TZD Study Team. Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study. J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):380-5. doi: 10.1136/jnnp.2008.159657. Epub 2008 Oct 31.
Results Reference
derived
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BOTOX® Versus Zanaflex® for the Treatment of Post-Stroke or Traumatic Brain Injury Upper Limb Spasticity
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