Quinine Sulfate for Muscle Cramps in Amyotrophic Lateral Sclerosis: A Randomized, Double-Blind Crossover Trial

Abstract

Introduction/aims: Many patients with amyotrophic lateral sclerosis (ALS) experience muscle cramps during the course of the disease. This study aimed to evaluate the efficacy of orally administered quinine sulfate for muscle cramps in ALS patients.

Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial in ALS patients experiencing daily muscle cramps. After a two-week run-in period, patients were assigned to receive 250 mg quinine sulfate once daily, followed by a placebo or vice versa. Each treatment period lasted 2 weeks and was followed by a 4-week washout period. Patients used a daily diary to rate muscle cramp intensity on the numeric rating scale (NRS) and record muscle cramp frequency. The primary outcome measure was change in cramp intensity; coprimary outcome measures were number of muscle cramps during daytime and nighttime.

Results: Data from four women and three men were included in the analysis, all of whom reported a notable reduction in cramp intensity and frequency, leading them to continue the medication. Quinine sulfate was well-tolerated, with two patients reporting mild tinnitus. Cramp intensity was significantly reduced by 48% (p = 0.042). Further, the number of daytime muscle cramps declined significantly (p = 0.024).

Discussion: Our findings suggest the potential efficacy of quinine sulfate in reducing muscle cramp intensity and frequency in ALS patients. However, the small sample size (n = 7) limits generalizability. Larger, multicenter studies are needed to confirm these results and fully assess its safety, serious adverse events, and therapeutic potential.

Keywords: ALS; efficacy; muscle cramps; placebo‐controlled trial; quinine sulfate.