Oral Branched-chain Amino Acid Supplementation for Decompensated Cirrhotic Patients

Official title

Oral Branched-chain Amino Acid Supplementation for Decompensated Cirrhotic Patients: a Pilot Study

Overview

The goal of this clinical trial is to compare the nutritional parameters after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL. The main questions it aims to answer are: 1. Would thigh muscle thickness change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? 2. Would triceps skin fold thickness, mid-arm circumferences, mid-arm muscle circumferences, skeletal muscle mass, appendicular skeletal muscle mass, skeletal muscle index and fat mass change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? 3. Would handgrip strength change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? 4. Would serum albumin change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? 5. Would score for cirrhotic severity such as Model for End-Stage Liver Disease-Sodium Score (MELD-Na score) and Child Turcotte Pugh Score change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? Participants will be asked to do following tasks: 1. Participants will be asked for basic information such as age, place of residence, and contact telephone number. 2. Participants will undergo measurements of weight, height, body mass index, skinfold thickness on the arms, circumference of the arms and legs, muscle mass, and body fat content using a body composition analyzer, both at the beginning and end of the research study. 3. Participants will perform grip strength measurements, at both the beginning and end of the research study. 4. Participants will undergo laboratory tests, including a complete blood count, liver and kidney function tests, blood clotting factors, and blood mineral levels, with a total blood volume of approximately 15 milliliters (1 tablespoon), collected twice during the study (at the beginning and end). 5. Participants will be administered supplements containing branched-chain amino acids (BCAA) twice a day for a total of 12 weeks. 6. Participants will be appointed for follow-up during the study, totaling 2 appointments at weeks 4 and 12. Side effects related to medication will be asked. 7. Participants will undergo ultrasound measurements of the right thigh to assess thigh muscle thickness, both at the beginning and end of the research study. 8. Participants will will complete questionnaires to assess your overall quality of life twice, both at the beginning and end of the research study.

Detailed description

The goal of this clinical trial is to compare the nutritional parameters after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL.

The main questions it aims to answer are:

1. Would thigh muscle thickness change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? 2. Would triceps skin fold thickness, mid-arm circumferences, mid-arm muscle circumferences, skeletal muscle mass, appendicular skeletal muscle mass, skeletal muscle index and fat mass change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? 3. Would handgrip strength change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? 4. Would serum albumin change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL? 5. Would score for cirrhotic severity such as Model for End-Stage Liver Disease-Sodium Score (MELD-Na score) and Child Turcotte Pugh Score change after 12-week supplementation of branched-chain amino acids in cirrhotic patients with ascites and serum albumin less than 3 g/dL?

Participants will be asked to do following tasks:

1. Participants will be asked for basic information such as age, place of residence, and contact telephone number. 2. Participants will undergo measurements of weight, height, body mass index, skinfold thickness on the arms, circumference of the arms and legs, muscle mass, and body fat content using a body composition analyzer, both at the beginning and end of the research study. 3. Participants will perform grip strength measurements, at both the beginning and end of the research study. 4. Participants will undergo laboratory tests, including a complete blood count, liver and kidney function tests, blood clotting factors, and blood mineral levels, with a total blood volume of approximately 15 milliliters (1 tablespoon), collected twice during the study (at the beginning and end). 5. Participants will be administered supplements containing branched-chain amino acids (BCAA) twice a day for a total of 12 weeks. 6. Participants will be appointed for follow-up during the study, totaling 2 appointments at weeks 4 and 12. Side effects related to medication will be asked. 7. Participants will undergo ultrasound measurements of the right thigh to assess thigh muscle thickness, both at the beginning and end of the research study. 8. Participants will will complete questionnaires to assess your overall quality of life twice, both at the beginning and end of the research study.

Interventions

• Drug Branched-chain amino acid
  Oral branched-chain amino acid is provided to the patients with a recommended daily intake of approximately 13.68 grams per day. Each sachet contains 6.84 grams of BCAA (valine 1.82 grams, leucine 3.29 grams, isoleucine 1.72 grams), total protein 17.08 grams, carbohydrates 25.48 grams, fat 5.66 grams, providing 221.2 kcal of energy. Each sachet weighs 52 grams and should be mixed with 150 ml of water. The recommended daily intake is 2 sachets, to be consumed after breakfast and dinner. The BCAA

Primary outcome measures

• thigh muscle thickness by ultrasound [Time frame: 12 weeks]
• Average Feather Index [Time frame: 12 weeks]
• Average Compression Index [Time frame: 12 weeks]

Secondary outcome measures (11)

• triceps skin fold thickness [Time frame: 12 weeks]
• mid-arm circumferences [Time frame: 12 weeks]
• mid-arm muscle circumferences [Time frame: 12 weeks]
• skeletal muscle mass [Time frame: 12 weeks]
• appendicular skeletal muscle mass [Time frame: 12 weeks]
• skeletal muscle index [Time frame: 12 weeks]
• Fat mass [Time frame: 12 weeks]
• Handgrip strength [Time frame: 12 weeks]
• MELD Na Score [Time frame: 12 weeks]
• Child Turcotte Pugh Score [Time frame: 12 weeks]
• Serum albumin [Time frame: 12 weeks]

Eligibility criteria

Inclusion criteria

• Cirrhotic patients of all etiology with aged of 18-85 years
• Clinically detectable ascites
• Serum albumin < 3 g/dL

Exclusion criteria

• Patients with hepatocellular carcinoma outside the Milan criteria.
• Patients with history of gastrointestinal bleeding and spontaneous bacterial peritonitis (SBP) within the last 3 months.
• Patients with acute on chronic liver failure (ACLF).
• Patients with uncontrollable chronic comorbidities, including chronic heart failure in NYHA stages 3-4, end stage kidney disease requiring dialysis, and chronic obstructive pulmonary disease Gold D.

5 .Patients who have undergone liver or kidney transplant. 6. Patients with Human Immunodeficiency Virus (HIV). 7. Pregnant or lactating patients. 8. Patients who have undergone large volume paracentesis (>5 liters) with intravenous albumin administration on the day of study enrollment. 9. Patients with a history of above-knee amputation surgery. 10. Patients with a history of receiving intravenous albumin administration every 1-2 weeks within the last one month.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Thailand · 1 center

• Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital — Bangkok

Publications

• Liu YB, Chen MK. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J Gastroenterol. 2022 Nov 7;28(41):5910-5930. doi: 10.3748/wjg.v28.i41.5910. PMID 36405106
• D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006 Jan;44(1):217-31. doi: 10.1016/j.jhep.2005.10.013. Epub 2005 Nov 9. No abstract available. PMID 16298014
• 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. PMID 30144956
• Maharshi S, Sharma BC, Srivastava S. Malnutrition in cirrhosis increases morbidity and mortality. J Gastroenterol Hepatol. 2015 Oct;30(10):1507-13. doi: 10.1111/jgh.12999. PMID 25974421
• 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. PMID 62115
• 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. PMID 30148232
• 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. PMID 28518283
• 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):6 PMID 35164698

Identifiers

NCT: NCT06121479 · SI 608/2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗