Oral Branched-chain Amino Acid Supplementation for Cirrhotic Patients With Sarcopenia

Sarcopenia Clinical Trial

— BCAASarcopenia  

Official title:

Oral Branched-chain Amino Acid Supplementation for Cirrhotic Patients With Sarcopenia: a Double-blinded Randomized Controlled Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06121492
• Other study ID #: SI 655/2023
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: November 15, 2023
• Est. completion date: December 31, 2025

Study information

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

Clinical Trial Summary

The goal of this clinical trial is to compare the nutritional parameters after 24-week supplementation of branched-chain amino acids in cirrhotic patients with low muscle mass.

The main questions it aims to answer are:

Is there the differences in the proportions of cirrhotic patients recovering from low muscle mass at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there the differences in the change of skeletal muscle index (SMI) measured by abdominal computed tomography (CT) at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in other indices related to low muscle mass, including appendicular skeletal muscle mass (ASM), ASM/height^2, handgrip strength, and 6-meter walk speed at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in the liver frailty index (LFI), consisting of handgrip strength, chair stands, and balance, at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in serum albumin levels, at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in severity of liver disease, including the Model for End-Stage Liver Disease-Sodium Score (MELD-Na score), Child-Turcotte-Pugh score, and liver stiffness measured by transient elastography at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group?

Participants will be asked to do following tasks:

Participants will be asked for basic information such as age, place of residence, and contact phone number.

Participants will undergo measurements of body weight, height, body mass index (BMI), muscle mass, and body fat content using a body composition analyzer, a total of 2 times (at the beginning and end of the research), and a lower abdominal computed tomography (CT) scan without additional radiation exposure, only once (at the end of the research) throughout the study.

Participants will be tested for muscle function, including handgrip strength, a 6-meter walk test, chair stands, and balance, all performed twice (at the beginning and end of the research).

Laboratory testing will include a complete blood count, liver and kidney function, blood clotting function, mineral levels, cholesterol, and glucose. Blood will be drawn a total of 2 times (at the beginning and end of the research) during the study, with each blood draw approximately 15 milliliters (1 tablespoon).

Transient elastography will be performed twice (at the beginning and end of the research) during the study, with each Transient elastography taking approximately 10 minutes.

Participants will be randomly assigned to either the group receiving branched chain amino acid (BCAA) medication or the placebo group, and you will take the assigned medication twice daily for a total of 24 weeks.

Participants will receive dietary and exercise recommendations from the research team and nutritionists in a group format, taking approximately 1 hour.

Participants will have follow-up appointments to monitor your condition three times during the study, at weeks 4, 12, and 24. These appointments will include inquiries about side effects from medication and placebo use, exercise, and dietary intake, each lasting approximately 30 minutes.

Participants will be asked to take photos of your daily meals for 3 days before meeting with the physician at weeks 4 and 12, to provide data for assessing your calorie intake. Participants can send these meal images via the online application, prepared by our research team. If participants are unable to do so, participants will be asked to keep a food diary and report your food and portion sizes to the research team.

Description:

The goal of this clinical trial is to compare the nutritional parameters after 24-week supplementation of branched-chain amino acids in cirrhotic patients with low muscle mass.

The main questions it aims to answer are:

Is there the differences in the proportions of cirrhotic patients recovering from low muscle mass at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there the differences in the change of skeletal muscle index (SMI) measured by abdominal computed tomography (CT) at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in other indices related to low muscle mass, including appendicular skeletal muscle mass (ASM), ASM/height^2, handgrip strength, and 6-meter walk speed at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in the liver frailty index (LFI), consisting of handgrip strength, chair stands, and balance, at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in serum albumin levels, at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in severity of liver disease, including the Model for End-Stage Liver Disease-Sodium Score (MELD-Na score), Child-Turcotte-Pugh score, and liver stiffness measured by transient elastography at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group?

Participants will be asked to do following tasks:

Participants will be asked for basic information such as age, place of residence, and contact phone number.

Participants will undergo measurements of body weight, height, body mass index (BMI), muscle mass, and body fat content using a body composition analyzer, a total of 2 times (at the beginning and end of the research), and a lower abdominal computed tomography (CT) scan without additional radiation exposure, only once (at the end of the research) throughout the study.

Participants will be tested for muscle function, including handgrip strength, a 6-meter walk test, chair stands, and balance, all performed twice (at the beginning and end of the research).

Laboratory testing will include a complete blood count, liver and kidney function, blood clotting function, mineral levels, cholesterol, and glucose. Blood will be drawn a total of 2 times (at the beginning and end of the research) during the study, with each blood draw approximately 15 milliliters (1 tablespoon).

Transient elastography will be performed twice (at the beginning and end of the research) during the study, with each Transient elastography taking approximately 10 minutes.

Participants will be randomly assigned to either the group receiving branched chain amino acid (BCAA) medication or the placebo group, and you will take the assigned medication twice daily for a total of 24 weeks.

Participants will receive dietary and exercise recommendations from the research team and nutritionists in a group format, taking approximately 1 hour.

Participants will have follow-up appointments to monitor your condition three times during the study, at weeks 4, 12, and 24. These appointments will include inquiries about side effects from medication and placebo use, exercise, and dietary intake, each lasting approximately 30 minutes.

Participants will be asked to take photos of your daily meals for 3 days before meeting with the physician at weeks 4 and 12, to provide data for assessing your calorie intake. Participants can send these meal images via the online application, prepared by our research team. If participants are unable to do so, participants will be asked to keep a food diary and report your food and portion sizes to the research team.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 86
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patients aged between 18 and 85 years.

• Patients who have been diagnosed with liver cirrhosis due to any etiology.

• Patients with sarcopenia as determined by a computed tomography scan within the last 3 months. For males, sarcopenia is defined as a Skeletal Muscle Index (SMI) less than 42 cm²/m², and for females, an SMI less than 38 cm²/m²

Exclusion Criteria:

• Patients with hepatocellular carcinoma outside the Milan criteria.

• Patients with Overt Hepatic Encephalopathy or gastrointestinal bleeding within the last 6 months.

• Patients with refractory ascites (ascites that does not respond to treatment).

• Patients in the advanced stage of cirrhosis with Child-Turcotte-Pugh (CTP) score C.

• Patients with acute-on-chronic liver failure (ACLF).

• Patients with uncontrollable decompensated comorbidities, including chronic heart failure classified as NYHA 3-4, patients with kidney disease requiring dialysis, patients with severe obstructive lung disease classified as Gold D, patients with other non-liver cancers requiring chemotherapy, and patients with chronic infections such as tuberculosis.

• Patients who have previously undergone liver or kidney transplantation.

• Patients with Human Immunodeficiency Virus (HIV) infection.

• Pregnant or breastfeeding patients.

Related Conditions & MeSH terms

• Cirrhosis of the Liver
• Fibrosis
• Liver Cirrhosis
• Sarcopenia

Intervention

Drug:
• Branched-chain amino acid
In the BCAA group, participants will receive oral BCAA for 24 weeks, with a daily dosage of approximately 13.68 g/day. Each sachet of BCAA will contain 6.84 g of BCAA (valine 1.82 g, leucine 3.29 g, isoleucine 1.72 g), total protein 17.08 g, carbohydrates 25.48 g, fat 5.66 g, providing 221.2 kcal of energy. Each sachet weighs 52 g and should be mixed with 150 ml of water. Participants will consume 2 sachets daily, one after breakfast and one after dinner.
• Placebo
In the placebo group, BCAA will be replaced with maltodextrin. Each sachet of the placebo will contain a total of 5.93 g of protein, 35.87 g of carbohydrates, 6.00 g of fat, providing 221.2 kcal of energy. Like the BCAA sachets, each placebo sachet will weigh 52 g and should be mixed with 150 ml of water. Participants in the placebo group will consume 2 sachets daily, one after breakfast and one after dinner.

Locations

Country	Name	City	State
Thailand	Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (22)

Charatcharoenwitthaya P, Tansakul E, Chaiyasoot K, Bandidniyamanon W, Charatcharoenwitthaya N. Dietary Composition and Its Association with Newly Diagnosed Nonalcoholic Fatty Liver Disease and Insulin Resistance. Nutrients. 2021 Dec 11;13(12):4438. doi: 10.3390/nu13124438. — View Citation

Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jul 1;48(4):601. doi: 10.1093/ageing/afz046. No abstract available. — 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 on nutrition in chronic liver disease. J Hepatol. 2019 Jan;70(1):172-193. doi: 10.1016/j.jhep.2018.06.024. Epub 2018 Aug 23. — View Citation

Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146. — 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

Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994 Mar;49(2):M85-94. doi: 10.1093/geronj/49.2.m85. — View Citation

Hernandez-Conde M, Llop E, Gomez-Pimpollo L, Fernandez Carrillo C, Rodriguez L, Van Den Brule E, Perello C, Lopez-Gomez M, Abad J, Martinez-Porras JL, Fernandez-Puga N, Ferre C, Trapero M, Fraga E, Calleja JL. Adding Branched-Chain Amino Acids to an Enhanced Standard-of-Care Treatment Improves Muscle Mass of Cirrhotic Patients With Sarcopenia: A Placebo-Controlled Trial. Am J Gastroenterol. 2021 Nov 1;116(11):2241-2249. doi: 10.14309/ajg.0000000000001301. — View Citation

Jaruvongvanich V, Thamtorawat S, Saiviroonporn P, Pisanuwongse A, Siriwanarangsun P. Sarcopenia as a Predictive Factor for Recurrence of Hepatocellular Carcinoma Following Radiofrequency Ablation. Asian Pac J Cancer Prev. 2023 Apr 1;24(4):1143-1150. doi: 10.31557/APJCP.2023.24.4.1143. — View Citation

Krell RW, Kaul DR, Martin AR, Englesbe MJ, Sonnenday CJ, Cai S, Malani PN. Association between sarcopenia and the risk of serious infection among adults undergoing liver transplantation. Liver Transpl. 2013 Dec;19(12):1396-402. doi: 10.1002/lt.23752. Epub 2013 Oct 21. — View Citation

Li AA, Kim D, Ahmed A. Association of Sarcopenia and NAFLD: An Overview. Clin Liver Dis (Hoboken). 2020 Sep 4;16(2):73-76. doi: 10.1002/cld.900. eCollection 2020 Aug. No abstract available. — View Citation

Luengpradidgun L, Chamroonkul N, Sripongpun P, Kaewdech A, Tanutit P, Ina N, Piratvisuth T. Utility of handgrip strength (HGS) and bioelectrical impedance analysis (BIA) in the diagnosis of sarcopenia in cirrhotic patients. BMC Gastroenterol. 2022 Mar 30;22(1):159. doi: 10.1186/s12876-022-02236-7. — View Citation

Mohta S, Anand A, Sharma S, Qamar S, Agarwal S, Gunjan D, Singh N, Madhusudhan KS, Pandey RM, Saraya A. Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia. Hepatol Int. 2022 Jun;16(3):680-690. doi: 10.1007/s12072-022-10334-7. Epub 2022 Apr 25. — View Citation

Nishikawa H, Shiraki M, Hiramatsu A, Moriya K, Hino K, Nishiguchi S. Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res. 2016 Sep;46(10):951-63. doi: 10.1111/hepr.12774. — View Citation

Roman E, Torrades MT, Nadal MJ, Cardenas G, Nieto JC, Vidal S, Bascunana H, Juarez C, Guarner C, Cordoba J, Soriano G. Randomized pilot study: effects of an exercise programme and leucine supplementation in patients with cirrhosis. Dig Dis Sci. 2014 Aug;59(8):1966-75. doi: 10.1007/s10620-014-3086-6. Epub 2014 Mar 6. — View Citation

Santilli V, Bernetti A, Mangone M, Paoloni M. Clinical definition of sarcopenia. Clin Cases Miner Bone Metab. 2014 Sep;11(3):177-80. — View Citation

Siramolpiwat S, Limthanetkul N, Pornthisarn B, Vilaichone RK, Chonprasertsuk S, Bhanthumkomol P, Nunanan P, Issariyakulkarn N. Branched-chain amino acids supplementation improves liver frailty index in frail compensated cirrhotic patients: a randomized controlled trial. BMC Gastroenterol. 2023 May 15;23(1):154. doi: 10.1186/s12876-023-02789-1. — View Citation

Sirisunhirun P, Bandidniyamanon W, Jrerattakon Y, Muangsomboon K, Pramyothin P, Nimanong S, Tanwandee T, Charatcharoenwitthaya P, Chainuvati S, Chotiyaputta W. Effect of a 12-week home-based exercise training program on aerobic capacity, muscle mass, liver and spleen stiffness, and quality of life in cirrhotic patients: a randomized controlled clinical trial. BMC Gastroenterol. 2022 Feb 14;22(1):66. doi: 10.1186/s12876-022-02147-7. — View Citation

Soeters PB, Fischer JE. Insulin, glucagon, aminoacid imbalance, and hepatic encephalopathy. Lancet. 1976 Oct 23;2(7991):880-2. doi: 10.1016/s0140-6736(76)90541-9. — View Citation

Tajiri K, Shimizu Y. Branched-chain amino acids in liver diseases. Transl Gastroenterol Hepatol. 2018 Jul 30;3:47. doi: 10.21037/tgh.2018.07.06. eCollection 2018. — View Citation

Tantai X, Liu Y, Yeo YH, Praktiknjo M, Mauro E, Hamaguchi Y, Engelmann C, Zhang P, Jeong JY, van Vugt JLA, Xiao H, Deng H, Gao X, Ye Q, Zhang J, Yang L, Cai Y, Liu Y, Liu N, Li Z, Han T, Kaido T, Sohn JH, Strassburg C, Berg T, Trebicka J, Hsu YC, IJzermans JNM, Wang J, Su GL, Ji F, Nguyen MH. Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis. J Hepatol. 2022 Mar;76(3):588-599. doi: 10.1016/j.jhep.2021.11.006. Epub 2021 Nov 14. — View Citation

Therakomen V, Petchlorlian A, Lakananurak N. Prevalence and risk factors of primary sarcopenia in community-dwelling outpatient elderly: a cross-sectional study. Sci Rep. 2020 Nov 11;10(1):19551. doi: 10.1038/s41598-020-75250-y. — View Citation

Zenith L, Meena N, Ramadi A, Yavari M, Harvey A, Carbonneau M, Ma M, Abraldes JG, Paterson I, Haykowsky MJ, Tandon P. Eight weeks of exercise training increases aerobic capacity and muscle mass and reduces fatigue in patients with cirrhosis. Clin Gastroenterol Hepatol. 2014 Nov;12(11):1920-6.e2. doi: 10.1016/j.cgh.2014.04.016. Epub 2014 Apr 24. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resolution of sarcopenia	To study the differences in the proportions of patients with resolution from sarcopenia measured by abdominal computed tomography at 24 weeks among cirrhotic patients with sarcopenia who received BCAA supplementation and the placebo group for 24 weeks. Resolution of sarcopenia implies better nutritional status and prognosis.	24 weeks
Secondary	change of skeletal muscle index (SMI) measured by abdominal computed tomography (CT)	To study the differences in the change of skeletal muscle index (SMI, centimeter^2/meter^2) measured by abdominal computed tomography (CT) at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group	24 weeks
Secondary	change of appendicular skeletal muscle mass (ASM)	To study changes in appendicular skeletal muscle mass (ASM, kg) measured by bioelectrical impedance at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group. Increase in appendicular skeletal muscle mass implies better nutritional status.	24 weeks
Secondary	change of index of appendicular skeletal muscle mass (ASM, kg) divided by height squared (meter^2)	To study changes in index of appendicular skeletal muscle mass (ASM, kg) divided by height squared (meter^2) at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group. Increase index of appendicular skeletal muscle mass (ASM, kg) divided by height squared (meter^2) implies better nutritional status.	24 weeks
Secondary	change of handgrip	To study changes in handgrip (kilograms) measured by digital handgrip strength dynamometer at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group. Increase in handgrip implies better physical performance.	24 weeks
Secondary	change of 6-meter walk speed	To study changes in 6-meter walk speed (meter/second) at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group. Increase in 6-meter walk speed implies better nutritional status.	24 weeks
Secondary	change of the liver frailty index (LFI)	To study changes in the liver frailty index (LFI), consisting of handgrip strength, chair stands, and balance, at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group.	24 weeks
Secondary	change of serum albumin	To study changes in serum albumin levels (grams/deciliters), at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group. Increase in serum albumin implies better nutritional status.	24 weeks
Secondary	change of MELD-Na score	To study changes in the Model for End-Stage Liver Disease-Sodium Score (MELD-Na score) at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group. Decrease of MELD-Na score implies improved severity of cirrhosis.	24 weeks
Secondary	change of Child-Turcotte-Pugh score	To study changes in Child-Turcotte-Pugh score at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group. Decrease of Child-Turcotte-Pugh score implies improved severity of cirrhosis.	24 weeks
Secondary	change of liver stiffness	To study changes in the liver stiffness (kPa) measured by transient elastography at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group. Decrease of liver stiffness implies improved severity of cirrhosis.	24 weeks