Dopamine Treatment in Children With Cerebral Palsy With Dystonia- A Double Blind Controlled Study

Study Overview
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Brief Summary
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Background: Cerebral palsy (CP) is the main cause of childhood immobility and is defined as a non progressive injury to the developing central nervous system in children younger than 3 years, resulting in neurological and musculoskeletal abnormalities. The main pathophysiological causes are encephalopathy of prematurity (periventricular leukomalacia) hypoxic ischemic encephalopathy. Infections, infracts and migration defects are other less common causes of CP. The brain injury leads to functional motor impairment impacting on daily activities commonly manifests as a movement disorder: pyramidal, leading to spasticity and extra-pyramidal leading to dystonia and chorea. In most cases extensive brain injury causes a mixed movement disorder. Dystonia is defined as involuntary muscle contractions causing twisting and abnormal postures. While the neurological underpinnings of CP remain unknown, a link between low dopamine and increased acetylcholine release has recently been reported in dystonia. Dopamine is considered the first line of treatment in children with dystonia and CP followed by anticholiergic treatment with trihexphenidyl. The recommendation of dopaminergic treatment is based on need to rule out dopamine-responsive-dystonia, a rare genetic disorder, and on single case study reporting improvement in CP. A double blind study support or refute the use of dopamine treatment for dystonic CP was never reported. Working hypothesis and Aims: In children with CP due to a clear underlying pathology, dopamine treatment will not improve daily function. Methods: the investigators will perform a double blinded randomized controlled crossover study. 50 children ages 4-18 years with a clear pathophysiological cause for CP will be enrolled. Each child will receive dopamine and placebo treatment for 2 weeks with a 2 week washout interval. Participants will be randomized into 2 groups; one will receive placebo followed by dopamine and the other vice versa. The primary outcome measure, goal-attainment-scale, and secondary outcome functional measures (such as box and blocks, 9 hole pegs, pronation/ supination, finger sequencing) will be assessed at the beginning and end of each treatment as well as parent questionnaires regarding satisfaction and side effects. Expected results: No functional improvement with dopamine treatment compared to placebo. Importance: supplying sufficient data to support or refute the use of dopamine treatment for dystonic CP. Probable implications to Medicine: this may lead to a change in medical treatment guidelines for children with CP.

Conditions
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Dystonic Cerebral Palsy

Intervention / Treatment
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* Drug: L- DOPA
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clear pathophysiological cause for CP disabling dystonia in upper limbs Exclusion Criteria: significant contractures psychiatric disorder

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DOPAMINE<br>Sinemet up to 10 mg/kg/day | Drug: L- DOPA<br>* Sinemet up to 10 mg/kg/ day increasing gradually for 2 weeks<br>|
| Placebo Comparator: Placebo<br>placebo | Drug: placebo<br>* placebo for 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QUEST quality of upper extremity skills test score before and after treatment | The QUEST is a measure designed to evaluate movement patterns and hand function in children with cerebral palsy. It is administered within a play context. Items are related to quality of movement, not to chronological age. There are 36 items assessing dissociated movements, grasp, protective extension, and weight bearing. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| box and blocks, 9 hole pegs, pronation/ supination, finger sequencing | Difference between test scores before and after treatment. Namely: of box transfered per minute time to complete the 9 hole pegs insertion. pronation/ supination per 20 seconds time to complete 5 finger sequencing rounds | 2 years |