The Effect of Branched-chain Amino Acid on the Improvement of Serum Albumin Level in Cirrhotic Patients With Ascites

The Effect of Branched-chain Amino Acid on the Improvement of Serum Albumin Level in Cirrhotic Patients With Ascites: A Multi-center, Randomized, Double-blind, Placebo-controlled, Investigator Initiated Clinical Trial

To compare the efficacy of branched-chain amino acid in serum albumin level in cirrhotic patients with ascites.

Study Overview

• Status: Unknown
• Conditions: Cirrhosis; Ascites
• Intervention / Treatment: Drug: Branched-chain Amino Acid; Drug: Placebo

Detailed Description

Branched-chain amino acid (BCAA) is known to reduce the relapse rate of liver cancer as it is associated with insulin resistance and has been reported to improve the progression of liver fibrosis when used in combination with an angiotensin-converting enzyme. With regard to the effect of liver function improvement, in a research conducted in South Korea, approximately 41.2% of the patients showed recovery of the normal albumin level when BCAA was administered to them for about 10 weeks during radiation therapy for liver cancer. Additionally, in other overseas researches, the changes in the values of total protein and albumin were significantly smaller in the patients who underwent transarterial chemoembolization (TACE) to whom BCAA was administered than in those to whom BCAA was not administered.

The hypothesis of this study is that the serum albumin value will be increased significantly in the cirrhotic patients with ascites to whom BCAA is administered than the patients to whom placebo is administered.

• Study Type: Interventional
• Enrollment (Anticipated): 188
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Principal Investigator: Jun Yong Park
  • Seoul, Korea, Republic of, 02841
    • Recruiting
    • Korea University Anam Hospital
    • Contact: Yeon Seok Seo, Professor
    • Principal Investigator: Yeon Seok Seo
  • Seoul, Korea, Republic of, 04401
    • Recruiting
    • Soonchunhyang University Seoul Hospital
    • Contact: Soung Won Jeong, Professor
    • Principal Investigator: Soung Won Jeong
  • Seoul, Korea, Republic of, 04763
    • Recruiting
    • Hanyang University Hospital
    • Principal Investigator: Dae won Jun
  • Seoul, Korea, Republic of, 02477
    • Recruiting
    • KyungHee University Hospital
    • Contact: Jae Jun Shim, Professor
    • Principal Investigator: Jae Jun Shim
  • Gangwon
    • Wonju, Gangwon, Korea, Republic of, 26426
      • Recruiting
      • Wonju Severance Christian Hospital
      • Principal Investigator: Moon Young Kim
  • Gyeonggi do
    • Bucheon, Gyeonggi do, Korea, Republic of, 14584
      • Recruiting
      • Soon Chun Hyang University Bucheon Hospital
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Not yet recruiting
      • Stanford University School of Medicine
      • Contact: W.Ray Kim, Professor; Phone Number: 650-725-6511; Email: wrkim@stanford.edu
      • Principal Investigator: W.Ray Kim, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 19 and ≤ 70 years;
• Presence of liver cirrhosis
• Serum albumin level ≤ 3.5g/dl, ultrasound or CT scan confirmed ascites (≥Grade 1)
• No administration of diuretics and BCAA within the past 1 week
• Voluntary consent to take part in this trial

Exclusion Criteria:

• Child-Pugh score > 12
• Having been diagnosed as HCC within the past 5 years
• Serum creatinine > 1.5mg/dl
• Serum bilirubin > 5.0mg/dl
• Presence of such complications as SBP, or hepatic encephalopathy(West Haven grade ≥ 3)
• Patients who experienced organ failure by acute exacerbation of liver cirrhosis within the past 1 month
• Presence of serious cardiac or respiratory disease
• Contraindicated to either diuretics or BCAA
• Having commenced anti-viral treatment against hepatitis C, B within the past 1 month
• Pregnant or lactating women
• Chronic alcohol taker
• Woman patients who do not agree to the contraception from baseline to 12 month
• Unsuitable patients judged by investigator
• Patients participating in another clinical trial within 1 month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BCAA group; Branched-chain amino acid, 4.15g, Tid	Drug: Branched-chain Amino Acid; BCAA (livact) will be administered 3 times a day during 24 weeks; Other Names: Livact®
PLACEBO_COMPARATOR: Placebo group; Placebo, 4.15g, Tid	Drug: Placebo; Placebo will be administered in the same way

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in serum albumin level	24 week

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in serum albumin level	12 week
Rates of albumin normalization	12, 24 week
Change in dose of diuretics	12, 24 week
Improvement in terms of severity of ascites (International Ascites Club grade)	24 week
Development rate of cirrhotic complications(including acute kidney injury, hepatic encephalopathy, variceal bleeding, peritonitis, etc)	24 week
Improvement in Child-Pugh score, class	24 week
Change in MELD, MELD-Na	24 week
Improvement in sarcopenia	24 week
Change in muscle mass	24 week
Change in muscle strength	24 week
Improvement in SF-36(short form-36)	24 week
Change in HOMA-IR(homeostatic model assessment-insulin resistance)	24 week

Other Outcome Measures

Outcome Measure	Time Frame
Change in serum cystatin c	12, 24 week
Change in HVPG(hepatic venous pressure gradient)	24 week
Radiological characteristics of patients who have reaction to the branched-chain amino acid agent	24 week
Change in serum creatinine	12, 24 week
Improvement on PHES (psychometric hepatic encephalopathy score)	24 week
Improvement on relative adrenal insufficiency	24 week

Collaborators and Investigators

• Sponsor: Soonchunhyang University Hospital
• Collaborators: Stanford University; Korea University Anam Hospital; Hanyang University; Severance Hospital; Wonju Severance Christian Hospital; Kyunghee University
• Investigators: Principal Investigator: Sang Gyune Kim, Soon Chun Hyang University

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (ANTICIPATED): June 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: April 21, 2016
• First Submitted That Met QC Criteria: April 26, 2016
• First Posted (ESTIMATE): April 29, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): September 2, 2016
• Last Update Submitted That Met QC Criteria: August 31, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ascites
• Other Study ID Numbers: LIV_ACT Trial_I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO