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

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

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.

Keywords: Botulinum Toxin-A; adult; cerebral palsy; pain; randomized controlled trial; spasticity.

Conflict of interest statement

KK has received speakers' honorarium from Ipsen and Allergan. The other authors have no conflicts of interest to report.

Copyright © 2021 Jacobson, Löwing, Kullander, Rydh and Tedroff.

Figures

Figure 1
Figure 1
Study patient flowchart. BoNT-A, botulinum toxin-A.
Figure 2
Figure 2
Main study outcomes. (A) Primary outcome. The number of treatment responders (defined as a reduction of ≥2 scale steps on the NRS) at 6 weeks after treatment, by treatment group. Test of proportions, p = 1.000. (B) Secondary outcome. The number of treatment responders (defined as change in categories of analgesics use) at 6 weeks after treatment, by treatment group. Test of proportions p = 0.429. (C) Secondary outcome. The number of treatment responders (defined as a reduction of mean interference score of ≥1 on the BPI) at 6 weeks after treatment, by treatment group. Test of proportions p = 1.000. BPI, Brief Pain Inventory; NRS, Numerical Rating Scale.
Figure 3
Figure 3
Exploratory analysis of mean pain intensity, by treatment group. BoNT-A, botulinum toxin-A; NRS, Numerical Rating Scale.
Figure 4
Figure 4
Exploratory analysis of individual patient pain intensity, by treatment group. Δ NRS represents change in pain intensity as compared to baseline. BoNT-A, botulinum toxin-A; NRS, Numerical Rating Scale.

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