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

This study has been completed.
Sponsor:
Collaborators:
United Cerebral Palsy Foundation
Don and Linda Carter Foundation
Crowley-Carter Foundation
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00122044
First received: July 18, 2005
Last updated: August 15, 2005
Last verified: July 2005
  Purpose

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.


Condition Intervention Phase
Dystonia
Drug: trihexyphenidyl
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Childhood Hypertonia of Central Origin: An Open Label Trial of Anticholinergic Treatment Effects

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Melbourne assessment of upper extremity function

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

Estimated Enrollment: 35
Study Start Date: January 2003
Estimated Study 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.

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00122044

Locations
United States, Alabama
University of Alabama School of Medicine
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Stanford, California, United States, 94305-5235
United States, Illinois
Rehabilitation Institute of Chicago
Chicago, Illinois, United States, 60611
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Texas
Texas Scottish Rite Hospital for Children
Dallas, Texas, United States, 75219
Sponsors and Collaborators
Stanford University
United Cerebral Palsy Foundation
Don and Linda Carter Foundation
Crowley-Carter Foundation
Investigators
Principal Investigator: Terence D Sanger, MD, PhD Stanford University
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00122044     History of Changes
Other Study ID Numbers: CHOCOLATE
Study First Received: July 18, 2005
Last Updated: August 15, 2005
Health Authority: United States: Institutional Review Board

Keywords provided by Stanford University:
childhood
cerebral palsy
dystonia
secondary
trihexyphenidyl
pediatric dystonia

Additional relevant MeSH terms:
Muscle Hypertonia
Dystonia
Dystonic Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
Neuromuscular Manifestations
Trihexyphenidyl
Cholinergic Antagonists
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscarinic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014