Oral Branched-chain Amino Acid Supplementation for Decompensated Cirrhotic Patients

Study Overview
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Brief Summary
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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: 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? 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? 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? 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? 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: Participants will be asked for basic information such as age, place of residence, and contact telephone number. 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. Participants will perform grip strength measurements, at both the beginning and end of the research study. 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). Participants will be administered supplements containing branched-chain amino acids (BCAA) twice a day for a total of 12 weeks. 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. Participants will undergo ultrasound measurements of the right thigh to assess thigh muscle thickness, both at the beginning and end of the research study. 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
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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: 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? 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? 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? 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? 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: Participants will be asked for basic information such as age, place of residence, and contact telephone number. 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. Participants will perform grip strength measurements, at both the beginning and end of the research study. 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). Participants will be administered supplements containing branched-chain amino acids (BCAA) twice a day for a total of 12 weeks. 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. Participants will undergo ultrasound measurements of the right thigh to assess thigh muscle thickness, both at the beginning and end of the research study. Participants will will complete questionnaires to assess your overall quality of life twice, both at the beginning and end of the research study.

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

Conditions
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Decompensated Cirrhosis and Ascites

Intervention / Treatment
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* Drug: Branched-chain amino acid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Oral branched-chain amino acid (BCAA) 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 provided to the patients comes in pre-packaged silver sachets, with the manufacturing date and expiration date indicated.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: branched-chain amino acid<br>Oral branched-chain amino acid (BCAA) 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 provided to the patients comes in pre-packaged silver sachets, with the manufacturing date and expiration date indicated. | Drug: Branched-chain amino acid<br>* 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 provided to the patients comes in pre-packaged silver sachets, with the manufacturing date and expiration date indicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| thigh muscle thickness by ultrasound | Thigh muscle thickness (centimeters) by ultrasound of right thigh will be performed according to these instructions 1. Measure the thickness of the right thigh muscles, which are the rectus femoris and vastus intermedius, at a position one-third between the upper edge of the patella bone to the iliac crest, with the patient lying flat. In that position, measure the thigh muscle thickness using two methods: a. Compression reading: Measure the muscle thickness by pressing the probe head until it cannot be compressed further. b. Feather weight reading: Measure the muscle thickness without applying pressure to the probe head. Take the muscle thickness measurements twice for each method, calculate their averages. Increase in thigh muscle thickness implies better nutritional status. | 12 weeks | 
| Average Feather Index | The Average Feather Index (cm/m2) will be calculated by taking average of thigh muscle thickness (centimeter) measured by feather weight reading divided by height (m^2). Increase in average feather index implies better nutritional status. | 12 weeks | 
| Average Compression Index | The Average Compression Index (cm/m2) will be calculated by taking average of thigh muscle thickness (centimeter) measured by compression weight reading divided by height (m^2). Increase in average compression index implies better nutritional status. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| triceps skin fold thickness | Triceps skin fold thickness (TSF, millimeter) will be measured using Lange skin fold caliper at midpoint of non dominant arm. | 12 weeks | 
| mid-arm circumferences | Mid-arm circumferences (MAC, centimeters) will be measured using standard measuring tape at midpoint of non dominant arm. Increase of mid-arm circumferences implies better nutritional status. | 12 weeks | 
| mid-arm muscle circumferences | Mid-arm muscle circumferences (MAMC, centimeters) will be obtained from calculating the following formula: MAMC (cm) = MAC - (0.314 × TSF [mm]). Increase of mid-arm muscle circumferences implies better nutritional status. | 12 weeks | 
| skeletal muscle mass | Skeletal muscle mass (kilograms) will be measured using bioelectrical impedance analysis. Increase of skeletal muscle mass implies better nutritional status. | 12 weeks | 
| appendicular skeletal muscle mass | Appendicular skeletal muscle mass (kilograms) will be measured using bioelectrical impedance analysis. Increase of appendicular skeletal muscle mass implies better nutritional status. | 12 weeks | 
| skeletal muscle index | Skeletal muscle index (kilograms/m^2) will be measured using bioelectrical impedance analysis. Increase of skeletal muscle index implies better nutritional status. | 12 weeks | 
| Fat mass | Fat mass (kilograms) will be measured using bioelectrical impedance analysis. | 12 weeks | 
| Handgrip strength | Handgrip strength (kilograms) will be measured three times for each hand using digital handgrip strength dynamometer. Increase of handgrip strength implies better physical performance. | 12 weeks | 
| MELD Na Score | MELD Na Score will be calculated at the start and end of study. Decrease of MELD Na Score implies improving of cirrhotic severity. | 12 weeks | 
| Child Turcotte Pugh Score | Child Turcotte Pugh Score will be calculated at the start and end of study. Decrease of Child Turcotte Pugh Score implies improving of cirrhotic severity. | 12 weeks | 
| Serum albumin | Serum albumin (gram/deciliter) will be measured at the start and end of study. Increase of serum albumin implies better nutritional status. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ascites, Decompensated cirrhosis, Branched-chain amino acid, Nutrition