Effect of Branched-chain Amino Acids (BCAA) to Muscle Cramps in Patients With Cirrhosis

Phase 4

Completed

• Conditions: Muscle Cramp; Cirrhosis; Quality of Life
• Interventions: Drug: Branched-chain Amino Acid; Drug: Placebo

• Registration Number: NCT05724485
• Lead Sponsor: Mahidol University

Brief Summary

The goal of this randomized controlled trial is to compare the efficacy and safety of branched-chain amino acids (BCAA) versus placebo for treating muscle cramps in cirrhotic patients. The main questions it aims to answer are:

* Compared the effect of BCAA versus placebo on muscle cramp frequency in cirrhotic patients

* Compared the effect of BCAA versus placebo on muscle cramp duration and severity in cirrhotic patients

* Compared the effect of BCAA versus placebo on quality of life in cirrhotic patients with muscle cramps Participants with cirrhosis who have experienced muscle cramps at least once per week will be randomized to receive either a placebo or 12.45 grams of BCAA orally per day for 12 weeks.

Detailed Description

Cirrhosis is a late-stage of fibrosis of the liver caused by many forms of liver disease. Muscle cramps are visible or palpable involuntary contraction part of the muscle. The prevalence of cramps in cirrhosis varied range from 31-78%. The pathophysiology of cramps in cirrhosis was explained by multiple mechanisms such as energy metabolism, nerve function, and plasma volume. Cramps significantly diminished the quality of life in cirrhotic patients.

Many drugs, vitamins, and minerals were studied for treating cramps in cirrhosis in previous studies but no clinical improvement, good randomized control studies, or side effects.

Branched-chain amino acids (BCAA) had been developed to correct this amino acid imbalance and helped to decrease the frequency of cramps and improve the quality of life in cirrhotic patients from previous studies but there were no control groups and a small number of patients were included. The aim of this study was to evaluate the efficacy and safety of BCAA for controlling muscle cramps in cirrhotic patients.

Study Timeline

• Study First Submitted: 2023-02-01
• Study First Submitted QC: 2023-02-09
• Study First Posted: 2023-02-13
• Study Start: 2023-04-01
• Primary Completion: 2023-10-31
• Study Completion: 2023-12-31
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-07
• Last Update Posted: 2024-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

• Age ≥ 18 years
• Muscle cramp ≥ 1 time per week
• Confirmed cirrhotic status (radiologic finding compatible with cirrhosis or liver stiffness measurement ≥ 12.5 kPa by transient elastography method or pathological confirm of cirrhosis)

Exclusion Criteria

• Allergy to BCAA
• Overt hepatic encephalopathy
• Hepatorenal syndrome
• Severe renal insufficiency; eGFR < 30
• Heart failure
• Peripheral arterial disease
• Active malignancies beyond hepatocellular carcinoma
• Heavy alcohol drinking (> 21g/day for men and >14g/day for women)
• Pregnancy or lactation
• Current use of BCAA within 3 months
• Recent adding or titrating diuretics within 4 weeks
• On current medications for muscle cramp relief such as vitamin E, taurine, carnitine, narcotic pain medications, baclofen, methocarbamol, other muscle relaxers, NSAIDs, or other antispastic agents.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BCAA group	Branched-chain Amino Acid	12.45 grams of branched-chain amino acids orally per day before bedtime for 12 weeks.
Placebo group	Placebo	12.45 grams of placebo (Maltodextrin) orally per day before bedtime for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change of muscle cramp frequency	12 weeks	Change from baseline in muscle cramp frequency by patient's diary record

Secondary Outcome Measures

Name	Time	Method
Change of muscle cramp duration	12 weeks	Change from baseline in muscle cramp duration by patient's diary record as minutes per muscle cramp events
Serum aspartate aminotransferase	12 weeks	Change of serum aspartate aminotransferase in cirrhotic patients with muscle cramps at the end of the study compared to baseline
Change of muscle cramp severity	12 weeks	Change from baseline in muscle cramp severity by patient's diary record as the visual analog scale that reported from 0 (no pain) to 10 (worst pain).
Quality of life in cirrhotic patients with muscle cramps	12 weeks	Change of quality of life in cirrhotic patients with muscle cramps at the end of the study compared to baseline by chronic liver disease questionnaire (CLDQ) that includes 29 items in the following domains: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function, and worry. The response of CLDQ results in 1 to 7 scales: ranging from "all of the time" to "none of the time".
Muscle mass in cirrhotic patients with muscle cramps	12 weeks	Change of muscle mass in cirrhotic patients with muscle cramps at the end of the study compared to baseline by bioelectrical impedance analysis (BIA)
Muscle strengthening in cirrhotic patients with muscle cramps	12 weeks	Change of muscle strength in cirrhotic patients with muscle cramps at the end of the study compared to baseline by hand grip strength measurement
Serum albumin	12 weeks	Change of serum albumin (g/dL) in cirrhotic patients with muscle cramps at the end of the study compared to baseline
Serum alanine aminotransferase	12 weeks	Change of serum alanine aminotransferase in cirrhotic patients with muscle cramps at the end of the study compared to baseline

Trial Locations

Locations (1)

Faculty of Medicine Siriraj Hospital, Mahidol University; 🇹🇭 Bangkok Noi, Bangkok, Thailand