"DOES MYOBLOC™ IMPROVE FUNCTIONAL HAND USE IN YOUNG CHILDREN WITH A HYPERTONIC UPPER EXTREMITY?"
Condition: Cerebral Palsy
MeSH terms: Cerebral Palsy
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      In children with cerebral palsy, stiffness of the arm can develop early and delay or prevent
      the acquisition of normal hand skills. Improvement in functional use of the hand may
      therefore be dependent upon early treatment of upper extremity hypertonia. We propose to test
      a series of injections of Myobloc™ in a non-randomized one-way crossover pilot clinical trial
      and dose-finding study, with clinical assessments and blinded video evaluations. Ten children
      age 2-17 years with increased tone at the elbow or wrist will be expected to complete the
      study. A 1-month baseline evaluation period will be followed by an injection of low-dose
      Myobloc™ to affected muscle(s) of the arm according to standardized per-kilogram dosing with
      a maximum of 25U/kg in each affected arm. Three months later, a second injection of up to
      50U/kg will be performed in each affected arm. Three months after the second dose, a third
      dose of up to 100U/kg will be performed in each affected arm. Neurological assessments will
      be performed at study entry, prior to each injection, and at 1 and 3 months following each
      injection. Routine physical therapy and non-study medications will be continued during the
      study.
    

Detailed description: 
      Subjects: 10 subjects age 2-17 years with hypertonia affecting one or both upper extremities,
      but without injections of neuromuscular blocking agents for six months prior to enrollment,
      or surgery on the upper extremity.

      Intervention: Injection of Myobloc™ in 2 sites per muscle for up to two muscles of each upper
      extremity (biceps, brachioradialis), at a maximum dose of 25Units/kg/arm for the first
      injection, a maximum of 50Units/kg/arm for the second injection, and a maximum of
      100Units/kg/arm for the third injection. If there is significant weakness or worsening of
      function following any injection, the dose will not be increased for subsequent injections.
      Injections will be performed after placement of topical anesthetic (ELA-MAX™ cream), using
      EMG guidance to identify active muscles contributing to hypertonia.

      Primary outcome measures: The primary outcome measure is the time it takes to complete
      maximum arm extension during voluntary reaching, measured from the coraco-acromial joint to
      the midpoint of the dorsum of the wrist. Change scores will be calculated between intake and
      1 month (baseline effect), 1 month and 2 months (first injection effect), 4 months and 5
      months (second injection effect), and 7 months and 8 months (third injection effect). A
      device called a Shape Tape (Measureand, Inc.) will be used to measure this outcome. Shape
      Tape is a flexible strip of portable spring steel with optic fiber that provides
      instantaneous readouts to a portable computer of bends and twists and other forms of movement
      capture that can be conducted in a clinical setting. The Shape Tape is fastened loosely to
      the body part under measurement (in this case, the subject's wrist and shoulder) with either
      medical-grade adhesive tape or Velcro. The shapetape is connected to a portable computer, and
      custom software allows measurement of the average velocity of hand movement during reaching.

      Secondary outcome measures: The rater will compare improvement or worsening in global arm
      function through the Unified Dystonia Rating Scale (UDRS), the motor subscale of the Unified
      Parkinson's Disease rating scale (UPDRS), and the Burke-Fahn-Marsden dystonia scale (BFM).
      Comparisons will be performed between intake and 1 month (baseline effect), 1 month and 2
      months (first injection effect), 4 months and 5 months (second injection effect), and 7
      months and 8 months (third injection effect). Other secondary measures include neurological
      examination, Ashworth spasticity scale, and comparisons of numerical stiffness measures as
      measured by the Rigidity Analyzer Device. A parent rating scale, the Pediatric Quality of
      Life Inventory (PedsQL), will be used to determine overall functional improvement.

      Statistical analysis: The outcomes will be tested at the 0.05 level of significance using
      repeated-measures analysis of variance (ANOVA) and the Friedman nonparametric test applied to
      the 4 repeated change scores for each of the primary and secondary outcome measures. Tests of
      significance for the secondary measures will be corrected for multiple comparisons.
    

Intervention name(s): Botulinum Toxin type B
Intervention type(s): Drug
Intervention MeSH terms: rimabotulinumtoxinB; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment