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

Study Overview
=================
Brief 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.

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.

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

Conditions
-----------------
Dystonia

Intervention / Treatment
-----------------
* Drug: trihexyphenidyl


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: trihexyphenidyl|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Melbourne assessment of upper extremity function |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Barry-Albright Dystonia Scale |  |  | 
| Burke-Fahn-Marsden Dystonia Scale |  |  | 
| Pediatric Outcomes Data Collection Instrument |  |  | 
| Pediatric Quality of Life |  |  | 
| Gross Motor Function Measure |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
childhood, cerebral palsy, dystonia, secondary, trihexyphenidyl, pediatric dystonia