Branched-chain Amino Acid Supplementation for Hepatocellular Carcinoma

NCT03908255 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: BCAA in HCC Intervention
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer death among men. While several new treatment options have recently become available, they are costly and have a potential for significant, adverse side effects. Many patients diagnosed with HCC also suffer from underlying liver disease, including cirrhosis. As many as 80-90% of patients diagnosed with HCC also have cirrhosis. Protein-energy malnutrition (PEM) in cirrhosis is as high as 65-90% and significantly increases the risk of morbidity and mortality as well as decreased quality of life. Branched-chain amino acid (BCAA) supplementation has been extensively studied for usefulness in liver disease, specifically to treat hepatic encephalopathy to and preserve and restore muscle mass. Maintenance of liver function and prevention of PEM are essential for improving outcomes in patients with HCC. Branched-chain amino acid supplementation in HCC has been studied extensively in China \& Japan with multiple studies showing improvements in liver function, progression-free survival, and overall survival. Additionally, patients in treatment groups have shown improvement in quality of life indicators. However, these results have yet to be replicated in the United States. Branched-chain amino acid supplementation may be a safe, low-cost approach to improve survival, liver function indicators, and quality of life for patients diagnosed with HCC. In this study, patients with primary HCC will be randomized to either a treatment group, which will receive standard of care and BCAA supplement or to a control group which will receive standard of care and a maltodextrin placebo. Both groups will receive liver-directed therapy including transarterial chemoembolization (TACE) and thermal ablation. All patients will complete a quality of life survey (FACT-Hep) at each visit.

Conditions

Hepatocellular Carcinoma; Cirrhosis; Liver Failure

Keywords

branch chain amino acid; nutritional supplement; malnutrition; decompensated liver failure

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival after after Day 0 of study (date of HCC treatment)

  Up to 24 months after enrollment

Secondary Outcomes (4)

• Tolerability and Use of BCAA Supplement: use of the supplement as greater than 50% compliance or less than 50% compliance

  At every clinic visit up to 24 months after enrollment

• Progression Free Survival

  Up to 24 months after enrollment

• Event Free Survival

  Up to 24 months after enrollment

• Quality of life using FACT-Hep

  Every 6 months up to 24 months after enrollment

Other Outcomes (11)

• Child Pugh Score

  At every clinic visit up to 24 months after enrollment

• Weight

  At every clinic visit up to 24 months after enrollment

• Height

  Every 3 months up to 24 months after enrollment

Study Arms (2)

Control Group

PLACEBO COMPARATOR

The control group will receive current standard of care (locoregional therapy of the liver, serial bloodwork and imaging, serial assessments in clinic), consume a maltodextrin placebo supplement beginning two weeks prior to liver directed therapy and continue supplementation for the following 12 months.

Other: maltodextrin

Intervention Group

EXPERIMENTAL

In the intervention group, patients will receive current standard of care (locoregional therapy of the liver, serial bloodwork and imaging, serial assessments in clinic) and consume BCAA supplements beginning two weeks prior to liver directed therapy and continue supplementation for the following 12 months.

Drug: Branch Chain Amino Acid

Interventions

Branch Chain Amino Acid DRUG

Nutritional supplementation

Also known as: Do Vitamins BCAA

Intervention Group

maltodextrin OTHER

Placebo

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have been diagnosed with HCC and deemed a candidate for nonsurgical local therapy (TACE and/or percutaneous ablation)
• Have a Child-Pugh score \< 6
• Are at least 18 years of age or older
• Otherwise healthy adults
• Provide written consent to participate

You may not qualify if:

• Have a diagnosis of renal failure
• Have a Child-Pugh score \> 6
• Consume \> 60g alcohol intake per day
• Have been diagnosed with branched-chain ketoaciduria (maple syrup urine disease)
• Have hepatic encephalopathy
• Have been diagnosed with a medical condition that warrants a low-protein diet
• Are currently taking insulin or metformin
• Pregnant women
• Younger than 18 years of age
• Are unable to provide consent
• Are incarcerated

Sponsors & Collaborators

• Louisiana State University Health Sciences Center in New Orleans: lead
• University Medical Center-New Orleans: collaborator

Study Sites (1)

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Related Publications (7)

• Takeda H, Nishikawa H, Iguchi E, Ohara Y, Sakamoto A, Saito S, Nishijima N, Nasu A, Komekado H, Kita R, Kimura T, Osaki Y. Effect of treatment with branched-chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma. Hepatol Res. 2014 Mar;44(3):302-12. doi: 10.1111/hepr.12125. Epub 2013 Apr 29.

  PMID: 23607614 RESULT

• Nojiri S, Fujiwara K, Shinkai N, Iio E, Joh T. Effects of branched-chain amino acid supplementation after radiofrequency ablation for hepatocellular carcinoma: A randomized trial. Nutrition. 2017 Jan;33:20-27. doi: 10.1016/j.nut.2016.07.013. Epub 2016 Aug 8.

  PMID: 27908546 RESULT

• Imanaka K, Ohkawa K, Tatsumi T, Katayama K, Inoue A, Imai Y, Oshita M, Iio S, Mita E, Fukui H, Yamada A, Nakanishi F, Inada M, Doi Y, Suzuki K, Kaneko A, Marubashi S, Ito Y, Fukui K, Sakamori R, Yakushijin T, Hiramatsu N, Hayashi N, Takehara T; Osaka Liver Forum. Impact of branched-chain amino acid supplementation on survival in patients with advanced hepatocellular carcinoma treated with sorafenib: A multicenter retrospective cohort study. Hepatol Res. 2016 Sep;46(10):1002-10. doi: 10.1111/hepr.12640. Epub 2016 Jan 26.

  PMID: 26690886 RESULT

• Chen L, Chen Y, Wang X, Li H, Zhang H, Gong J, Shen S, Yin W, Hu H. Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis. Nutr J. 2015 Jul 9;14:67. doi: 10.1186/s12937-015-0056-6.

  PMID: 26155840 RESULT

• Au KP, Chan SC, Chok KS, Chan AC, Cheung TT, Ng KK, Lo CM. Child-Pugh Parameters and Platelet Count as an Alternative to ICG Test for Assessing Liver Function for Major Hepatectomy. HPB Surg. 2017;2017:2948030. doi: 10.1155/2017/2948030. Epub 2017 Aug 29.

  PMID: 28951631 RESULT

• Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsayes KM, Bashir MR, Kono Y, Do RK, Mitchell DG, Singal AG, Tang A, Sirlin CB. Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology. 2018 Dec;289(3):816-830. doi: 10.1148/radiol.2018181494. Epub 2018 Sep 25.

  PMID: 30251931 RESULT

• Gmur A, Kolly P, Knopfli M, Dufour JF. FACT-Hep increases the accuracy of survival prediction in HCC patients when added to ECOG Performance Status. Liver Int. 2018 Aug;38(8):1468-1474. doi: 10.1111/liv.13711. Epub 2018 Feb 20.

  PMID: 29389088 RESULT

Related Links

• LI-RADS v2018
• FACT-Hep questionnaire

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Fibrosis; Liver Failure; Malnutrition

Interventions

Amino Acids; maltodextrin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hepatic Insufficiency; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins

Study Officials

• Richard H Marshall, MD

  Louisiana State University Health Sciences Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study design will be a double-blinded, randomized clinical control trial in which treatment-naïve patients diagnosed with HCC will be screened at baseline before being randomized to either a treatment group, which will receive standard of care and BCAA supplement, or to a control group which will receive standard of care and a maltodextrin placebo. Both groups will receive liver directed therapy including transarterial chemoembolization (TACE) at baseline. In the intervention group, patients will receive current standard of care and consume BCAA supplements beginning two weeks prior to liver directed therapy and continue supplementation for the following 12 months. The control group will receive current standard of care, consume a maltodextrin placebo beginning two weeks prior to liver directed therapy and continue supplementation for the following 12 months.

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: April 9, 2019
• Study Start: June 1, 2021
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2023
• Last Updated: January 28, 2022

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The time frame for data sharing will begin after initial publication and will extend for 5 years. After this point, data will be purged from secured servers and will no longer be available for sharing.
• Access Criteria: A request for data will be made through the principal investigator of this study, who is responsible for data storage. Requests will be made to local Institutional Review Boards prior to de-identified data release.

Locations

US (1)