J Korean Med Sci. 2022;37(7):e56.

Efficacy and Safety of Pregabalin for Muscle Cramps in Liver Cirrhosis: A Double-Blind Randomized Controlled Trial.

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제1저자 안소현 · 교신저자 김원, 홍윤호

PMID 35191232 PMC8860769 DOI 10.3346/jkms.2022.37.e56 IF 3.2 소화기내과

소속 (6)

Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
Department of Neurology, Neuroscience Research Institute, Seoul National University Medical Research Council, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea. yhh@snu.ac.kr.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Department of Neurology, Ajou University Medical Center, Ajou University College of Medicine, Suwon, Korea.
Department of Neurology, Konkuk University Hospital, Konkuk University College of Medicine, Seoul, Korea.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea. drwon1@snu.ac.kr.

Abstract

BACKGROUND Muscle cramp is possibly related to peripheral nerve hyperexcitability (PNH), and one of the most debilitating symptoms frequently encountered in patients with liver cirrhosis. We investigated whether pregabalin, a gamma-aminobutyric acid analogue, can suppress neuronal excitability and reduce muscle cramps in cirrhotic patients.

METHODS We conducted a randomized, double-blind, placebo-controlled trial in which study participants with cirrhosis from a single tertiary center were enrolled. Primary endpoint was the relative change in cramp frequency from the run-in to standard dose treatment phase (4 weeks per each). Secondary endpoints included the responder rate, and the changes in cramp frequency during sleep, pain intensity, health-related quality of life (Liver Disease Quality of Life Instrument, Short Form-36) and electrophysiological measures of PNH.

RESULTS This study was terminated early because of insufficient accrual. 80% (n = 56) of the target number of participants (n = 70) were randomized to pregabalin (n = 29) or placebo (n = 27). Median baseline frequency of muscle cramps (interquartile range) was 5.8 (3.5-10) per week in the pregabalin group and 6.5 (4.0-10) in the placebo group (P = 0.970). The primary analysis showed a significant reduction in cramp frequency with pregabalin compared to placebo (-36% vs. 4.5% for the percentage change, P = 0.010). Secondary outcomes did not differ significantly between the two groups. Adverse effects with pregabalin were mainly dizziness and lethargy.

CONCLUSION With multiple problems emerging from premature termination in mind, the results suggested an acceptable safety profile and favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients.

TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01271660.

Keywords

Liver CirrhosisMuscle CrampPeripheral NervePregabalin

Figures

**Fig. 1** Trial profile. Efficacy and safety analyses were performed with the modified intention-to-treat population set, defined as all randomized study participants who received at least one dose of the study drug.

**Fig. 2** Changes in the relative frequency of muscle cramps. (A) Box plots of the relative change in the frequency of muscle cramps from baseline (run-in phase) to the standard dose treatment phase (4 weeks per each) (P = 0.010 by the Wilcoxon rank sum test). (B) Responder analyses over a range of cut-off points for the minimum percentage change. P values calculated using the Fisher's exact test.

그림 출처: PubMed Central 공개 논문 (PMC8860769)

Conflict of interest statement

YHH received research grants from Astellas Pharma Korea, the National Research Foundation of Korea, the Korea Health Industry Development Institute, and received honoraria for consultancies from Mitsubishi Tanabe Pharma Korea. WK received research grants from Pfizer, Gilead, Novartis, Roche, Springbank, Altimmune, Ildong, MSD, BMS, DaeWoong, BuKwang, Pharmaessentia, Dicerna, GreenCross, Celgene, and Enyo, and received honoraria for consultancies or lectures from Gilead, Boehringer-Ingelheim, Novo Nordisk, Samil, Ildong, LG Chemistry, HK inno.N, GreenCross, BuKwang, Standigm, PharmaKing, KOBIOLABS, and Eisai, and holds stocks from KOBIOLABS and Lepidyne. Other authors have no potential conflicts of interest to disclose.

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