A First Clinical Trial on Botulinum Toxin-A for Chronic Muscle-Related Pain in Cerebral Palsy.

Dan Jacobson,Britt-Marie Rydh,Kristina Tedroff,Kristina Löwing,Kjell Kullander

doi:10.3389/fneur.2021.696218

Abstract

Objective: To test if botulinum toxin-A (BoNT-A) is effective in reducing chronic muscle-related pain in adults with spastic cerebral palsy (CP), as compared to placebo.Design: A single-center, double-blind, parallel, randomized placebo-controlled trial. The design included an interim analysis to allow for confirmatory analysis, as well as pilot study outcomes.Setting: Tertiary university hospital.Participants: Adults with spastic CP and chronic pain associated with spastic muscle(s).Intervention: Treatment was one session of electromyographically guided intramuscular injections of either BoNT-A or placebo normosaline.Main Study Outcomes: The primary outcome was the proportion who achieved a reduction of pain intensity of two or more steps on the Numerical Rating Scale 6 weeks after treatment.Results: Fifty individuals were screened for eligibility, of whom 16 were included (10 female, 6 male, mean age = 32 years, SD = 13.3 years). The randomization yielded eight participants per treatment arm, and all completed the study as randomized. The study was stopped at the interim analysis due to a low probability, under a preset threshold, of a positive primary outcome. Four individuals were treatment responders in the BoNT-A group for the primary outcome compared to five responders in the placebo group (p = 1.000). Adverse events were mild to moderate. In exploratory analysis, the BoNT-A group had a trend of continuing reduction of pain at the last follow-up, after the primary endpoint.Conclusions: This study did not find evidence that BoNT-A was superior to placebo at the desired effect size (number needed to treat of 2.5) at 6 weeks after treatment.Trial registration:ClinicalTrials.gov: NCT02434549

Highlights

One important health issue in adults with cerebral palsy (CP) is pain
The most common causes for exclusion were that the individual presented with pain that appeared only infrequently or that the pain was unrelated to regional spasticity
The study was terminated at the interim analysis due to futility of the primary outcome

Summary

Introduction

One important health issue in adults with cerebral palsy (CP) is pain. Pain, often chronic in character, is reported to affect up to 76% of adults with CP [1]. To the best of our knowledge, no clinical trial has been published where pain reduction has been the primary outcome in adults with CP and in only one case as an exploratory variable [2]. Spasticity is characterized by a velocity-dependent resistance of a muscle to stretch [7] and could, hypothetically, cause mechanical stresses on musculoskeletal structures with secondary development of chronic pain. Spasticity is a quite frequent finding in neurological disorders, many aspects of spasticity differ because of the etiology. These include, but are not limited to, the onset of spasticity after an event, the development or change of spasticity over time, and the possible neuroradiological findings that are considered to correlate with the spasticity. Findings from studies on spasticity reduction in multiple sclerosis or traumatic brain injury, for example, cannot be directly extrapolated onto CP

Results

Discussion

Conclusion