## Protocol Section
### Identification Module
**NCT ID:** NCT06121479

**Brief Title:** 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

#### Organization Study ID Info
**ID:** SI 608/2023
#### Organization
**Class:** OTHER
**Full Name:** Mahidol University
### Status Module
#### Completion Date
**Date:** 2024-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-11-18

**Type:** ACTUAL

**Last Update Submit Date:** 2023-11-14

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-06-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-11-13

**Type:** ACTUAL

**Status Verified Date:** 2023-11

#### Study First Post Date
**Date:** 2023-11-08
**Type:** ACTUAL
**Study First Submit Date:** 2023-11-01
**Study First Submit QC Date:** 2023-11-07
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Mahidol University

#### Responsible Party

**Investigator Affiliation:** Mahidol University

**Investigator Full Name:** Phunchai Charatcharoenwitthaya

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

### Conditions Module

**Conditions:**

- Decompensated Cirrhosis and Ascites

**Keywords:**

- Decompensated cirrhosis

- Branched-chain amino acid

- Nutrition

- Ascites

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention 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 Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**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.

**Intervention Names:**

- Drug: Branched-chain amino acid

**Label:** branched-chain amino acid

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- branched-chain amino acid

**Description:** 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.

**Name:** Branched-chain amino acid

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** thigh muscle thickness by ultrasound

**Time Frame:** 12 weeks

**Description:** 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.

**Measure:** Average Feather Index

**Time Frame:** 12 weeks

**Description:** 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.

**Measure:** Average Compression Index

**Time Frame:** 12 weeks

#### Secondary Outcomes

**Description:** Triceps skin fold thickness (TSF, millimeter) will be measured using Lange skin fold caliper at midpoint of non dominant arm.

**Measure:** triceps skin fold thickness

**Time Frame:** 12 weeks

**Description:** 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.

**Measure:** mid-arm circumferences

**Time Frame:** 12 weeks

**Description:** 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.

**Measure:** mid-arm muscle circumferences

**Time Frame:** 12 weeks

**Description:** Skeletal muscle mass (kilograms) will be measured using bioelectrical impedance analysis. Increase of skeletal muscle mass implies better nutritional status.

**Measure:** skeletal muscle mass

**Time Frame:** 12 weeks

**Description:** Appendicular skeletal muscle mass (kilograms) will be measured using bioelectrical impedance analysis. Increase of appendicular skeletal muscle mass implies better nutritional status.

**Measure:** appendicular skeletal muscle mass

**Time Frame:** 12 weeks

**Description:** Skeletal muscle index (kilograms/m\^2) will be measured using bioelectrical impedance analysis. Increase of skeletal muscle index implies better nutritional status.

**Measure:** skeletal muscle index

**Time Frame:** 12 weeks

**Description:** Fat mass (kilograms) will be measured using bioelectrical impedance analysis.

**Measure:** Fat mass

**Time Frame:** 12 weeks

**Description:** Handgrip strength (kilograms) will be measured three times for each hand using digital handgrip strength dynamometer. Increase of handgrip strength implies better physical performance.

**Measure:** Handgrip strength

**Time Frame:** 12 weeks

**Description:** MELD Na Score will be calculated at the start and end of study. Decrease of MELD Na Score implies improving of cirrhotic severity.

**Measure:** MELD Na Score

**Time Frame:** 12 weeks

**Description:** 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.

**Measure:** Child Turcotte Pugh Score

**Time Frame:** 12 weeks

**Description:** Serum albumin (gram/deciliter) will be measured at the start and end of study. Increase of serum albumin implies better nutritional status.

**Measure:** Serum albumin

**Time Frame:** 12 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

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

Exclusion Criteria:

1. Patients with hepatocellular carcinoma outside the Milan criteria.
2. Patients with history of gastrointestinal bleeding and spontaneous bacterial peritonitis (SBP) within the last 3 months.
3. Patients with acute on chronic liver failure (ACLF).
4. 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.

**Maximum Age:** 85 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** WASIT.WONGTRAKUL@GMAIL.COM

**Name:** WASIT WONGTRAKUL, M.D.

**Phone:** +66822702898

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Bangkok

**Contacts:**

***Contact 1:***

- **Email:** wasit.wongtrakul@gmail.com

- **Name:** WASIT WONGTRAKUL, M.D.

- **Phone:** 66822702898

- **Role:** CONTACT

***Contact 2:***

- **Name:** Phunchai Charatcharoenwitthaya, M.D.

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Thailand

**Facility:** Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

**Status:** RECRUITING

**Zip:** 10700

#### Overall Officials

**Official 1:**

**Affiliation:** Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

**Name:** Phunchai Charatcharoenwitthaya, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** In order to protect patients' confidentiality, we will not share individual participant data.

**IPD Sharing:** NO

### References Module

#### References

**Citation:** 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

**Citation:** 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

**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.

**PMID:** 30144956

**Citation:** 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

**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.

**PMID:** 62115

**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.

**PMID:** 30148232

**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.

**PMID:** 28518283

**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.

**PMID:** 35164698

**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.

**PMID:** 34074812

**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.

**PMID:** 37189033

**Citation:** Haj Ali S, Abu Sneineh A, Hasweh R. Nutritional assessment in patients with liver cirrhosis. World J Hepatol. 2022 Sep 27;14(9):1694-1703. doi: 10.4254/wjh.v14.i9.1694.

**PMID:** 36185724

**Citation:** Tandon P, Low G, Mourtzakis M, Zenith L, Myers RP, Abraldes JG, Shaheen AA, Qamar H, Mansoor N, Carbonneau M, Ismond K, Mann S, Alaboudy A, Ma M. A Model to Identify Sarcopenia in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2016 Oct;14(10):1473-1480.e3. doi: 10.1016/j.cgh.2016.04.040. Epub 2016 May 14. Erratum In: Clin Gastroenterol Hepatol. 2022 Jun;20(6):1423.

**PMID:** 27189915

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M11103

- Name: Liver Cirrhosis

- Relevance: LOW

- As Found: Unknown

- ID: M4509

- Name: Ascites

- Relevance: HIGH

- As Found: Ascites

- ID: M8485

- Name: Fibrosis

- Relevance: HIGH

- As Found: Cirrhosis

### Condition Browse Module - Meshes

- ID: D000005355

- Term: Fibrosis

- ID: D000001201

- Term: Ascites

### Intervention Browse Module - Browse Branches

- Abbrev: AA

- Name: Amino Acids

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: T10

- Name: Leucine

- Relevance: LOW

- As Found: Unknown

- ID: T23

- Name: Valine

- Relevance: LOW

- As Found: Unknown

- ID: T9

- Name: Isoleucine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
