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

Dystonia Clinical Trial

Official title:

Childhood Hypertonia of Central Origin: An Open Label Trial of Anticholinergic Treatment Effects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00122044
• Other study ID #: CHOCOLATE
• Status: Completed
• Phase: Phase 2
• First received: July 18, 2005
• Last updated: May 21, 2014
• Start date: January 2003
• Est. completion date: December 2004

Study information

• Verified date: May 2014
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 2004
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 17 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dystonia

Intervention

Drug:
• trihexyphenidyl

Locations

Country	Name	City	State
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	University of Alabama School of Medicine	Birmingham	Alabama
United States	Rehabilitation Institute of Chicago	Chicago	Illinois
United States	Texas Scottish Rite Hospital for Children	Dallas	Texas
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Stanford University	Stanford	California

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern California	Crowley Carter Foundation, Don and Linda Carter Foundation, United Cerebral Palsy Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Melbourne assessment of upper extremity function
Secondary	Barry-Albright Dystonia Scale
Secondary	Burke-Fahn-Marsden Dystonia Scale
Secondary	Pediatric Outcomes Data Collection Instrument
Secondary	Pediatric Quality of Life
Secondary	Gross Motor Function Measure

External Links

•   Information on childhood dystonia and other movement disorders