Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects

Overview

This study is an open-label trial of trihexyphenidyl in children with upper extremity dystonia due to cerebral palsy. It is hypothesized that trihexyphenidyl in doses up to 0.75mg/kg/day would be well-tolerated and show significant changes on the Melbourne scale of upper extremity function.

Full Title of Study: “Childhood Hypertonia of Central Origin: An Open Label Trial of Anticholinergic Treatment Effects”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2004

Detailed Description

BACKGROUND: Although trihexyphenidyl has been used to treat both primary and secondary dystonia in children, previous studies have not investigated efficacy in secondary dystonia. We describe the results of a prospective, open-label, multi-center trial of high-dose trihexyphenidyl in children with secondary dystonia of the arms due to cerebral palsy. METHODS: Twenty-six children age 4-15 years with cerebral palsy and dystonia that impairs function of the dominant upper extremity were enrolled. All children were given trihexyphenidyl at increasing doses over 9 weeks up to 0.75mg/kg/day. Trihexyphenidyl was subsequently tapered over 5 weeks. Visits occurred at baseline, 9 weeks, and 15 weeks. The primary outcome measure was the Melbourne assessment of upper extremity function, tested in the dominant arm. RESULTS: Three children withdrew due to non-serious adverse events (chorea, drug rash, hyperactivity). 3 children reduced dosage due to non-serious adverse events. The 23 children who completed the study showed a significant improvement in arm function at 15 weeks (p=0.045) but not at 9 weeks. Post-hoc analysis showed that a subgroup (N=10) with hyperkinetic dystonia worsened at 9 weeks (p=0.04) but subsequently returned to baseline following taper of the medicine. CONCLUSIONS: Trihexyphenidyl appears to be safe and effective for treatment of arm dystonia in children with cerebral palsy. Children with hyperkinetic dystonia may worsen. A larger randomized prospective trial is needed to confirm these results.

Interventions

  • Drug: trihexyphenidyl

Clinical Trial Outcome Measures

Primary Measures

  • Melbourne assessment of upper extremity function

Secondary Measures

  • Barry-Albright Dystonia Scale
  • Burke-Fahn-Marsden Dystonia Scale
  • Pediatric Outcomes Data Collection Instrument
  • Pediatric Quality of Life
  • Gross Motor Function Measure

Participating in This Clinical Trial

Inclusion Criteria

  • Dystonia in the dominant upper extremity Exclusion Criteria:

  • Complete absence of voluntary movement in the affected hands, wrists, and elbows – Severe weakness in the dominant upper extremity (MRC grade < 4) – Passive range of motion at the hand, wrist or elbow less than 80% of normal – Current use of medications for dystonia (anticholinergics, L-dopa, baclofen, diazepam, tizanidine, tetrabenazine, reserpine, and others) – Changes in the subject's physical therapy regimen for the duration of the 15-week study – Prior use of trihexyphenidyl or other anticholinergic therapy for dystonia. – History of surgery on the dominant upper extremity or cervical spine – Botulinum toxin injection in the dominant upper extremity within the previous 6 months – Current or prior implantation of an intrathecal baclofen pump, deep brain stimulator, or other device to treat dystonia or spasticity – Concurrent acute or chronic medical condition (such as frequent seizures, heart disease, or asthma) that could adversely affect motor performance or the safety of testing – Presence of diurnal fluctuations or other clinical signs and symptoms suggesting an inborn error of metabolism, a family history of dystonia suggesting a genetic dystonia, or dystonia due to injury after the neonatal period (including toxin exposure, trauma, or medication-induced) – History of allergic or adverse reaction to trihexyphenidyl or other anticholinergic medications – Current complaint of urinary retention requiring treatment. – History of glaucoma, or family history of glaucoma with onset before age 40

Gender Eligibility: All

Minimum Age: 5 Years

Maximum Age: 17 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Southern California
  • Collaborator
    • United Cerebral Palsy Foundation
  • Provider of Information About this Clinical Study
    • Principal Investigator: Terence Sanger, Associate Professor – University of Southern California
  • Overall Official(s)
    • Terence D Sanger, MD, PhD, Principal Investigator, Stanford University

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