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

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.

Study Overview

• Status: Unknown
• Conditions: Dystonic Cerebral Palsy
• Intervention / Treatment: Drug: L- DOPA; Drug: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Recruiting
    • Shaare Zedek Medical Center
    • Contact: Hilla Ben- Pazi, MD; Email: Benpazi@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clear pathophysiological cause for CP
• disabling dystonia in upper limbs

Exclusion Criteria:

• significant contractures
• psychiatric disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center

Publications and helpful links

General Publications

• Pozin I, Bdolah-Abram T, Ben-Pazi H. Levodopa does not improve function in individuals with dystonic cerebral palsy. J Child Neurol. 2014 Apr;29(4):534-7. doi: 10.1177/0883073812473645. Epub 2013 Jan 24.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Anticipated): May 1, 2012
• Study Completion (Anticipated): August 1, 2012

Study Registration Dates

• First Submitted: June 6, 2010
• First Submitted That Met QC Criteria: May 25, 2011
• First Posted (Estimate): May 26, 2011

Study Record Updates

• Last Update Posted (Estimate): May 27, 2011
• Last Update Submitted That Met QC Criteria: May 26, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Cerebral Palsy; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: -L- Dopa-Cerebral Palsy