Effect of Psychostimulant Medications on Physical Function in Children with Cerebral Palsy: Protocol for a Pilot Randomized Controlled Trial

Background: Cerebral palsy (CP) is prevalent non-progressive disorder that leads to impairment of movement (i.e., spasticity), posture, and balance, which affects movements that are required for functioning, such as walking and upper extremity tasks. Current medical treatments showed efficacy in improving motor performance but have considerable side effects. Emerging off-label use of central nervous system (CNS) medications for improving motor performance showed promising results in children with CP and other populations. The aim of this study was to describe a protocol for a pilot randomized controlled trial (RCT) to examine safety, tolerability, and efficacy of methylphenidate (MPH) and modafinil on spasticity and motor performance in children with CP. Methods: A protocol study for a pilot, triple-masked, and placebo controlled RCT (class I trial following the American Academy of Neurology criteria) with blinded patients, outcome assessors, and intervention delivery team. Eligible children should be diagnosed with CP levels I and II based on the gross motor function classification system aged between seven and 12 years. Thirty-six children with CP will be randomized into three groups to receive: a) MPH (2.5 mg of MPH + 100 mg placebo), b) modafinil (100mg modafinil + 2.5 placebo), and c) placebo group (2.5 mg and 100 mg placebo), in addition to physical therapy for 12. Primary outcomes include the gross motor function measure-66 and the modified Ashworth scale. Secondary outcomes include the timed-up and go, five time sit to stand test, modified clinical test for sensory interaction of balance, and ten-meter walk tests. Discussion: This study protocol outlines a pilot (RCT) aimed at assessing the impact of MPH and modafinil on motor performance and spasticity in children with CP. The study aims to establish the safety and tolerability of these medications and expects to observe improvements in motor function (GMFM–66 and MAS) in the MPH and modafinil groups compared to a placebo group. These potential improvements could enhance the overall quality of life for children with CP and may have cost-saving implications for healthcare systems by reducing the burden associated with CP-related motor impairments. Trial Registration: This trial was registered in clinicaltrials.gov (NCT05675098).