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

Quality of Life Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05724485
• Other study ID #: Si 1071/2020
• Status: Completed
• Phase: Phase 4
• Start date: April 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2024
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cirrhosis
• Fibrosis
• Liver Cirrhosis
• Muscle Cramp
• Quality of Life
• Spasm

Intervention

Drug:
• Branched-chain Amino Acid
12.45 grams of BCAA orally per day before bedtime
• Placebo
12.45 grams of Maltodextrin orally per day before bedtime

Locations

Country	Name	City	State
Thailand	Faculty of Medicine Siriraj Hospital, Mahidol University	Bangkok Noi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (23)

Abd-Elsalam S, Arafa M, Elkadeem M, Elfert A, Soliman S, Elkhalawany W, Badawi R. Randomized-controlled trial of methocarbamol as a novel treatment for muscle cramps in cirrhotic patients. Eur J Gastroenterol Hepatol. 2019 Apr;31(4):499-502. doi: 10.1097/ — View Citation

Angeli P, Albino G, Carraro P, Dalla Pria M, Merkel C, Caregaro L, De Bei E, Bortoluzzi A, Plebani M, Gatta A. Cirrhosis and muscle cramps: evidence of a causal relationship. Hepatology. 1996 Feb;23(2):264-73. doi: 10.1002/hep.510230211. — View Citation

Angeli P, Fasolato S, Mazza E, Okolicsanyi L, Maresio G, Velo E, Galioto A, Salinas F, D'Aquino M, Sticca A, Gatta A. Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical — View Citation

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Chatrath H, Liangpunsakul S, Ghabril M, Otte J, Chalasani N, Vuppalanchi R. Prevalence and morbidity associated with muscle cramps in patients with cirrhosis. Am J Med. 2012 Oct;125(10):1019-25. doi: 10.1016/j.amjmed.2012.03.012. Epub 2012 Jul 24. — View Citation

Elfert AA, Abo Ali L, Soliman S, Zakaria S, Shehab El-Din I, Elkhalawany W, Abd-Elsalam S. Randomized placebo-controlled study of baclofen in the treatment of muscle cramps in patients with liver cirrhosis. Eur J Gastroenterol Hepatol. 2016 Nov;28(11):128 — View Citation

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 — View Citation

Gluud LL, Dam G, Les I, Marchesini G, Borre M, Aagaard NK, Vilstrup H. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2017 May 18;5(5):CD001939. doi: 10.1002/14651858.CD001939.pub4. — View Citation

Hidaka H, Nakazawa T, Kutsukake S, Yamazaki Y, Aoki I, Nakano S, Asaba N, Minamino T, Takada J, Tanaka Y, Okuwaki Y, Watanabe M, Shibuya A, Koizumi W. The efficacy of nocturnal administration of branched-chain amino acid granules to improve quality of lif — View Citation

Kawaguchi T, Izumi N, Charlton MR, Sata M. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology. 2011 Sep 2;54(3):1063-70. doi: 10.1002/hep.24412. Epub 2011 Jun 23. — View Citation

Ko CH, Wu SJ, Wang ST, Chang YF, Chang CS, Kuan TS, Chuang HY, Chang CM, Chou W, Wu CH. Effects of enriched branched-chain amino acid supplementation on sarcopenia. Aging (Albany NY). 2020 Jul 26;12(14):15091-15103. doi: 10.18632/aging.103576. Epub 2020 J — View Citation

Marchesini G, Bianchi G, Amodio P, Salerno F, Merli M, Panella C, Loguercio C, Apolone G, Niero M, Abbiati R; Italian Study Group for quality of life in cirrhosis. Factors associated with poor health-related quality of life of patients with cirrhosis. Gas — View Citation

Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, Rossi Fanelli F, Abbiati R; Italian BCAA Study Group. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology — View Citation

Mehta SS, Fallon MB. Muscle cramps in liver disease. Clin Gastroenterol Hepatol. 2013 Nov;11(11):1385-91; quiz e80. doi: 10.1016/j.cgh.2013.03.017. Epub 2013 Mar 28. — View Citation

Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, Kato M, Nakamura T, Higuchi K, Nishiguchi S, Kumada H; Long-Term Survival Study Group. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Cl — View Citation

Nakaya Y, Okita K, Suzuki K, Moriwaki H, Kato A, Miwa Y, Shiraishi K, Okuda H, Onji M, Kanazawa H, Tsubouchi H, Kato S, Kaito M, Watanabe A, Habu D, Ito S, Ishikawa T, Kawamura N, Arakawa Y; Hepatic Nutritional Therapy (HNT) Study Group. BCAA-enriched sna — View Citation

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Sako K, Imamura Y, Nishimata H, Tahara K, Kubozono O, Tsubouchi H. Branched-chain amino acids supplements in the late evening decrease the frequency of muscle cramps with advanced hepatic cirrhosis. Hepatol Res. 2003 Aug;26(4):327-329. doi: 10.1016/s1386- — View Citation

Sawada Y, Shiraki M, Iwasa M, Hiraoka A, Nakanishi H, Karino Y, Nakajima T, Miyaaki H, Kawaguchi T, Yoshiji H, Okita K, Koike K. The effects of diuretic use and the presence of ascites on muscle cramps in patients with cirrhosis: a nationwide study. J Gas — View Citation

Sobhonslidsuk A, Silpakit C, Kongsakon R, Satitpornkul P, Sripetch C. Chronic liver disease questionnaire: translation and validation in Thais. World J Gastroenterol. 2004 Jul 1;10(13):1954-7. doi: 10.3748/wjg.v10.i13.1954. — View Citation

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Vidot H, Carey S, Allman-Farinelli M, Shackel N. Systematic review: the treatment of muscle cramps in patients with cirrhosis. Aliment Pharmacol Ther. 2014 Aug;40(3):221-32. doi: 10.1111/apt.12827. Epub 2014 Jun 18. — View Citation

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of muscle cramp frequency	Change from baseline in muscle cramp frequency by patient's diary record	12 weeks
Secondary	Change of muscle cramp duration	Change from baseline in muscle cramp duration by patient's diary record as minutes per muscle cramp events	12 weeks
Secondary	Change of muscle cramp severity	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).	12 weeks
Secondary	Quality of life in cirrhotic patients with muscle cramps	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".	12 weeks
Secondary	Muscle mass in cirrhotic patients with muscle cramps	Change of muscle mass in cirrhotic patients with muscle cramps at the end of the study compared to baseline by bioelectrical impedance analysis (BIA)	12 weeks
Secondary	Muscle strengthening in cirrhotic patients with muscle cramps	Change of muscle strength in cirrhotic patients with muscle cramps at the end of the study compared to baseline by hand grip strength measurement	12 weeks
Secondary	Serum albumin	Change of serum albumin (g/dL) in cirrhotic patients with muscle cramps at the end of the study compared to baseline	12 weeks
Secondary	Serum alanine aminotransferase	Change of serum alanine aminotransferase in cirrhotic patients with muscle cramps at the end of the study compared to baseline	12 weeks
Secondary	Serum aspartate aminotransferase	Change of serum aspartate aminotransferase in cirrhotic patients with muscle cramps at the end of the study compared to baseline	12 weeks