Clinical trial NCT06121492: Oral Branched-chain Amino Acid Supplementation for Cirrhotic Patients with Sarcopenia
Official title: Oral Branched-chain Amino Acid Supplementation for Cirrhotic Patients with Sarcopenia: a Double-blinded Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Sarcopenia
Cirrhosis of the Liver
Keywords: sarcopenia
cirrhosis
Branched-chain amino acids
nutrition
Lead sponsor: Mahidol University
Sponsor class: OTHER
First posted: 2023-11-08
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants will be randomly and blindly divided into two groups: (branched-chain amino acids) BCAA group and the placebo group, using a 1:1 ratio, with each group consisting of 43 individuals. The blinded participants will take either BCAA or placebo for 24 weeks.
Primary purpose: TREATMENT

Brief 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 an upper 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.

Detailed 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 an upper 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Resolution of sarcopenia
timeFrame: 24 weeks
Secondary outcomes:
measure: change of skeletal muscle index (SMI) measured by abdominal computed tomography (CT)
timeFrame: 24 weeks
measure: change of appendicular skeletal muscle mass (ASM)
timeFrame: 24 weeks
measure: change of index of appendicular skeletal muscle mass (ASM, kg) divided by height squared (meter^2)
timeFrame: 24 weeks
measure: change of handgrip
timeFrame: 24 weeks
measure: change of 6-meter walk speed
timeFrame: 24 weeks
measure: change of the liver frailty index (LFI)
timeFrame: 24 weeks
measure: change of serum albumin
timeFrame: 24 weeks
measure: change of MELD-Na score
timeFrame: 24 weeks
measure: change of Child-Turcotte-Pugh score
timeFrame: 24 weeks
measure: change of liver stiffness
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Study officials:
affiliation: Mahidol University
name: Phunchai Charatcharoenwitthaya, M.D.
role: PRINCIPAL_INVESTIGATOR
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