Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of Central Nervous System Stimulants, represented by Methylphenidate and Modafinil, compared to placebo control on motor performance in children with Cerebral Palsy. This study will be a triple-masked study per the American Academy of Neurology guidelines for clinical trials.

Detailed Description
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Cerebral Palsy (CP) is a neurological disorder that commonly cause disability and limit physical function in children, and this disability persists into adulthood. There are several treatment options for motor impairments associated with CP, including oral medications (diazepam or related benzodiazepines, baclofen, dantrolene, and tizanidine hydrochloride), intraspinal infusion (baclofen), paralyzing agents (Botulinum toxin), and surgical interventions (dorsal rhizotomy). However, these interventions have drawbacks that could impact their benefits, such as drowsiness with oral medications and permanent change in muscle tone with the rhizotomy surgery. Other rehabilitation interventions showed significant improvements in motor function such as constraint-induced movement therapy (CIMT) and strength training. A few researchers attempted using central nervous system stimulants (i.e., Modafinil [Provigil]) off-label for improving motor control and reducing spasticity in children with CP. Another medication that has been used for motor impairments is Methylphenidate (MPH), also a central nervous system stimulant. However, this medication was used for improving muscle tone and motor performance in children with Attention-deficit/Hyperactivity Disorder (ADHD), but not in children with CP. MPH is useful for children with combined CP and ADHD and showed beneficial results for ADHD symptoms and behavioral outcomes with minimal side effects. Therefore, the purpose of this pilot randomized controlled trial (RCT) is to examine the effects of Central Nervous System (CNS) stimulants (Modafinil and MPH) vs. placebo in addition to physical therapy intervention on gross motor function and spasticity in children with CP.

Official Title
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Effect of Central Nervous System Stimulants on Physical Function in Children With Cerebral Palsy: A Pilot Randomized Controlled Trial

Conditions
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Neurodevelopmental Disorders, Cerebral Palsy

Intervention / Treatment
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* Drug: Methylphenidate
* Drug: Modafinil
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children diagnosed with spastic diplegic or quadriplegic CP by a physician. Children aged between 7-12 years old. Children with CP classified as level I & II based on the gross motor function classification system (GMFCS). Children with CP that are receiving physical therapy for ≥ 3 months. Exclusion Criteria: Children that had a seizure attack in the past 6 months Children that have been diagnosed with attention deficit/ hyperactivity disorder (ADHD) Children that had any surgery within the last 6 months Children that has lower-extremity contractures determined by the passive range of motion (hips, knees, and ankles) Children that use medications that interfere with spasticity (e.g., Baclofen)

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 12 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylphenidate<br>Participants in this group will receive 2.5mg Methylphenidate and 100mg placebo (Modafinil shape) in addition to physical therapy program | Drug: Methylphenidate<br>* This medication is a psychostimulant medication and is usually prescribed for individuals with Attention-Deficit/Hyperactivity Disorder to manage ADHD behavioral symptoms<br>* Other names: Ritalin;|
| Experimental: Modafinil<br>Participants in this group will receive 100mg Modafinil and 2.5mg placebo (Methylphenidate shape) in addition to physical therapy program | Drug: Modafinil<br>* This medication is a Central Nervous System stimulant and is usually used to treat neurological conditions, including Narcolepsy<br>* Other names: Provigil;|
| Placebo Comparator: Placebo<br>Participants in this group will receive 2.5mg placebo (Methylphenidate shape) and 100mg placebo (Modafinil shape) in addition to physical therapy program | Other: Placebo<br>* Participant will receive placebo tablets (Methylphenidate and Modafinil shape)<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gross motor function measure (GMFM) | To determine changes in functional motor abilities. | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 
| Modified Ashworth Scale (MAS) | To determine changes in spasticity | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body height | To determine body height | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 
| Timed up and go (TUG) | To assess dynamic balance | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 
| Five times sit to stand test (5x Sit-To-Stand Test /5XSST) | To assess the change in functional strength | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 
| Modified clinical test for sensory interaction of balance (MCTSIB) | To assess static balance | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 
| Ten-meter walk test (10MWT) (normal pace) | To assess change in gait speed | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 
| 2-Minutes Walking Test (normal pace) | To determine changes in fatigue | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 
| The University of California, San Diego Shortness of Breath Questionnaire (UCSDSOBQ) | To determine changes in respiratory function | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 
| Body weight | To determine body weight | Baseline, 6 weeks, 12 weeks, and 24 weeks after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methylphenidate, Modafinil, physical therapy, motor performance, spasticity, physical function