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Comparative Efficacy of Three Preparations of Botox-A in Treating Spasticity

This study has been completed.
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Gerard Francisco, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT00178646
First received: September 12, 2005
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

The study seeks to compare the effectiveness of three preparations of BOTOX-A® in treating muscle tightness and spasms in the feet and ankles of people with stroke.


Condition Intervention Phase
Stroke
Brain Injuries
Spasticity
Drug: Botox
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparative Efficacy of Three Preparations of Botox-A in Treating Spasticity

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Ashworth Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Range of Motion [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: January 2002
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Botox, 150 units prepared as 100 units/ml
Drug: Botox
Botox 75-150 units, single treatment only
Other Name: generic name: botulinum toxin type A
Active Comparator: 2
Botox 150 units, prepared as 50 units/ml.
Drug: Botox
Botox 75-150 units, single treatment only
Other Name: generic name: botulinum toxin type A
Active Comparator: 3
Botox 75 units, prepared as 25 units/ml.
Drug: Botox
Botox 75-150 units, single treatment only
Other Name: generic name: botulinum toxin type A

Detailed Description:

Spasticity is one of the most debilitating complications of neurologic conditions, such as stroke, brain injury, spinal cord injury, cerebral palsy, and multiple sclerosis. Although the exact pathophysiology is unknown, it is believed to result from an imbalance of ascending excitatory influences on and descending inhibitory components of the central nervous system. Clinically, spasticity manifests as abnormally increased muscle tone, associated with loss of range of motion, increased muscle stretch reflexes, clonus, weakness, and incoordination. If inadequately treated, spasticity leads to more disability and increase health care costs. Common complications of inadequately treated spasticity include joint and muscle contracture, pain, difficulty with performing activities of daily living and hygiene, and impaired transfers and ambulation.

Acquired brain injuries (ABI), including stroke, traumatic brain injury, and encephalopathy, often lead to long-term impairments, including spasticity. In severe cases, spasticity is difficult and frustrating to treat in this patient population, since the individuals may not tolerate the side effects of conventional therapies because of ABI-related deficits in arousal and cognition. Systemic medications, such as baclofen and tizanidine, are effective in controlling spasticity; however, they may also cause sleepiness and drowsiness, and impair memory and thinking processes---adverse effects that individuals with ABI may not tolerate.

Thus, "local" treatments, such as neurolysis and chemodenervation using botulinum toxin, have become superior treatment options in individuals with ABI, since they are devoid of the usual side effects of systemic medications. They are also effective in controlling spasticity, yet they do not impair arousal and cognition. The medical literature is replete with reports of the efficacy of botulinum toxin-A in the management of spasticity. Thus, the current challenge for clinicians and researchers at this time is to find ways to further enhance the efficacy of botulinum toxin. One way to achieve this is by exploiting certain properties of the toxin. Animal studies and clinical experience have shown that the effects of the drug is dose-dependent. One other property is the flexibility in preparing the volume of drug injected. Since botulinum toxin, as it is currently available (as BOTOX-A®) in the United States, requires reconstitution with preservative-free saline, there is flexibility for clinicians to manipulate the volume of solution that will be administered, without altering the dose.

We recently completed a trial comparing the effects of two volume preparations of BOTOX-A® on wrist and finger flexor spasticity of individuals with ABI. One group of patients received BOTOX-A® prepared as 100 units/cc, while another received BOTOX-A® prepared as 50 units/cc. Although there was no statistically significant difference between the two groups, there was a trend in favor of the group that received the higher volume, i.e.; they appeared to improve more based on decrease in muscle tone (measured by the Modified Ashworth Scale). This was compared by the clinician's global impression that the high volume group improved more. The latter measure achieved statistical significance. One possible reason for the absence of statistical significance was that the "high" volume (50 units/cc) was not high enough. Thus, we are proposing this study to investigate the comparative effects of three preparations of BOTOX-A®.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria -

  • Spasticity resulting from ABI (stroke, including vascular malformations, traumatic brain injury)
  • Ashworth Score (resting) of at least 2 of the primary ankle plantarflexor (gastrocnemius)
  • Onset of primary illness at least six months prior to study inclusion
  • At least 12 years of age

Exclusion Criteria -

  • Hypersensitivity or allergy to botulinum toxin
  • History of myasthenia gravis or other neuromuscular disease
  • Current use of aminoglycosides
  • Botulinum toxin or phenol injection to study limb within six months prior to recruitment
  • Current use of other spasmolytic drug, such as diazepam, baclofen, dantrolene, tizanidine
  • Presence of contracture or significant muscle atrophy
  • Pregnancy
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00178646

Locations
United States, New Jersey
Kessler Institute for Rehabiliation
West Orange, New Jersey, United States, 07052
United States, Texas
Memorial Hermann Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Allergan
Investigators
Principal Investigator: Gerard E Francisco, MD University of Texas
  More Information

Publications:
Responsible Party: Gerard Francisco, Clinical Professor and Chairman - Physical Medicine and Rehabilitation, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT00178646     History of Changes
Other Study ID Numbers: HSC-MS-01-103
Study First Received: September 12, 2005
Last Updated: December 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center, Houston:
Stroke
Brain Injuries
Spasticity
Botulinum Toxins

Additional relevant MeSH terms:
Brain Injuries
Muscle Spasticity
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Muscle Hypertonia
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Manifestations
Signs and Symptoms
Trauma, Nervous System
Wounds and Injuries
Botulinum Toxins
Botulinum Toxins, Type A
Anti-Dyskinesia Agents
Central Nervous System Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014