Keywords:spasticy , stroke , TBI
Dysport has been investigated in a number of studies of upper and lower limb spasticity of various etiologies in adults and in children. In these studies improvements in spasticity and muscle tone were observed in targeted muscles. Dysport is licensed in over 75 countries for various indications including the treatment of adult upper limb spasticity. The maximum dose for this
indication is 1000 U.
The upper limb is often adversely affected by stroke or traumatic brain injury, resulting in spasticity which can affect subject’s activities of daily life. However,
few studies have assessed at the same time the effects of BTX on muscle tone,
passive and active function, and spasticity in this subject population.
The present phase III, multicentre, prospective, double blind, randomised, placebo
controlled, single treatment cycle study has been designed to assess the efficacy of
Dysport for the treatment of upper limb spasticity in adult subjects with hemiparesis
due to stroke or traumatic brain injury. Effects of muscle tone on the primary
targeted muscle group (using the Modified Ashworth Scale (MAS)) will be assessed
as primary criterion.
Both the efficacy and safety profile of Dysport administered at 500 U and 1000 U
will be compared to placebo. Long term safety and efficacy will be assessed in an
open label extension study for all eligible subjects.
Principle Investigator: Steven Edgley
Principle Department: Physical Medicine & Rehab
All subjects must satisfy the following inclusion criteria to be eligible for the study:
Provision of written informed consent prior to any study related procedures.
Between 18 and 80 years of age, inclusive.
Subjects who had only one clinically defined stroke episode, as defined by the World Health Organisation (WHO) criteria or who have had one brain trauma, or subjects who had a nonevolutive lesion diagnosed prior to the stroke and in the same hemisphere as shown by brain imaging (i.e. scan or MRI).
At least 6 months post-stroke or traumatic brain injury.
Modified Ashworth Scale (MAS) score ≥2 in the primary targeted muscle group for toxin naïve subjects or MAS score ≥3 in the primary targeted muscle group for toxin non-naïve subjects at least 4 months after the last BTX injection, of any serotype.
Disability Assessment Scale (DAS) score ≥2 on the PTT.
Spasticity angle ≥10° in the primary targeted muscle group.
Modified Frenchay Scale (MFS) overall score (average of all task scores) between 1 and 8 (including limit values).
Subjects are to be excluded if any of the following apply:
(1) Major limitation in the passive ROM at the affected elbow, wrist and fingers, as defined by:
- Maximum passive elbow extension <150° (0° corresponding to the minimal stretch of the elbow flexors, which corresponds to a fully flexed elbow position),
- Maximum passive wrist extension <70°, (0° corresponding to the minimal stretch of the wrist flexors, which corresponds to a fully flexed wrist position),
- Maximum passive finger extension <70° (0° corresponding to the minimal stretch of the extrinsic finger flexors, which corresponds to a formed fist with the second phalanx parallel to the metacarpal).
(2) Physiotherapy initiated less than 4 weeks before entry or expected to be initiated during the study.
(3) Previous treatment with BTX of any type within 4 months prior to study entry for any condition.
(4) Subjects likely to be treated with BTX of any type in the lower limb during the course of this double blind study.
(5) Previous primary or secondary non response to any BTXs for the targeted condition.
(6) Previous surgery to treat spasticity of the affected upper limb.
(7) Previous treatment with phenol and/or alcohol in the treated upper limb anytime before the study.
(8) Any medical condition (including severe dysphagia or airway disease) that may increase, in the opinion of the Investigator, the likelihood of AEs related to BTX treatment.
(9) Major neurological impairment other than spastic paresis (including major proprioceptive ataxia or apraxia on the paretic side) that could negatively impact on the functional performance of the subject.
(10) Known disease of the neuromuscular junction (such as Lambert-Eaton myasthenic syndrome or myasthenia gravis).
(11) Inability to understand protocol procedures and requirements which, in the opinion of the Investigator, could negatively impact on protocol compliance.
(12) Known sensitivity to BTX or any excipient of Dysport.
(13) Infection at the injection site(s).
(14) Unwillingness or inability to comply with the protocol.
(15) Current or planned treatment with any drug that interferes either directly or indirectly with neuromuscular function (i.e. aminoglycosides) within the last 4 weeks prior to study treatment.
(16) Pregnant women, or premenopausal women not willing to use contraceptive measures throughout the duration of the study.
(17) Treatment with a new investigational drug in the 4 weeks prior to enrolment into the study or scheduled to receive such a drug during the study period.
(18) Any underlying disease (not associated with the stroke or traumatic brain injury) likely to affect upper limb function and/or muscle tone and/or spasticity.
(19) Any medical condition (or laboratory finding) which, in the opinion of the Investigator, may compromise compliance with the objectives and/or procedures of this protocol or preclude the administration of BTX.
(20) Subjects treated or likely to be treated with intrathecal baclofen during the course of the study or during the 4 weeks before study entry.