Intravenous BCAA for HE in ACLF (BCAA-HE-ACLF)

NCT05700695 | Completed Phase 1

• 1 other identifier: IEC/04/2022-2385
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

This multi-centric study analyses the effect of intravenous branched-chain amino acids (BCAA) on overt HE in patients with ACLF. The investigators aim to study the efficacy of combining intravenous BCAA with lactulose versus lactulose alone, ammonia measures, endotoxin, metabolomics, and cerebral edema in the medical management of overt HE in patients with ACLF. The study will also access the impact on overall survival and improvement in the grade of HE.

Conditions

Hepatic Encephalopathy; Acute-On-Chronic Liver Failure

Keywords

Hepatic Encephalopathy; Acute-On-Chronic Liver Failure; Neurological Dysfunction; Metabolomics; Systemic Inflammations; Branch Chain Amino Acid; bispectral index; Cerebral edema; Lactulose

Outcome Measures

Primary Outcomes (1)

• Survival

  Survival assessment will be made by recording all deaths

  Day 28

Secondary Outcomes (10)

• Reduction of arterial ammonia Level

  Day 3

• Reduction of arterial ammonia Level

  Day 7

• Assessment of cerebral edema

  Discharge form Hospital and 3 month of episode of HE

• Prevention/reduction of cerebral edema based on optic nerve sheath diameter (ONSD)

  72 Hours

• Reduction of consciousness recovery time among survivors

  Day 28

Study Arms (2)

Experiential Arm

EXPERIMENTAL

Drug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose

Drug: Branch Chain Amino Acid; Drug: Lactulose

Comparator Arm

ACTIVE COMPARATOR

Drug: Lactulose + Placebo of IV BCAA solution

Drug: Lactulose

Interventions

Branch Chain Amino Acid DRUG

Intravenous branched chain amino acids will be given for 3 days to patients in experimental arm

Experiential Arm

Lactulose DRUG

Oral lactulose will be given to patients in both arms

Comparator Arm; Experiential Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years
• Either gender
• Patients with ACLF (CANONIC definition) of any etiology with HE ≥grade 2 as per West-Haven Criteria

You may not qualify if:

• Those who do not consent to participate in the study
• Patients with structural brain lesions or stroke
• Inability to obtain informed consent from patient or relatives
• Severe preexisting cardiopulmonary disease
• Renal dysfunction (S. Creatinine ≥ 2mg/dL)
• Pregnancy/Lactation
• Post liver transplant patients
• HIV infection
• Patients who are on psychoactive drugs, like sedatives or antidepressants
• Patients who are too sick to carry out the protocol.

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead
• Amrita Institute of Medical Sciences & Research Center: collaborator
• Asian Institute of Gastroenterology, India: collaborator
• All India Institute of Medical Sciences, Bhubaneswar: collaborator
• Kalinga Institute of Medical Sciences, Bhubaneswar: collaborator

Study Sites (1)

Dr. Madhumita Premkumar

Chandigarh, Chandigarh, 160012, India

Location

Related Publications (11)

• Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA. Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol. 2011 Apr;54(4):640-9. doi: 10.1016/j.jhep.2010.07.045. Epub 2010 Dec 1.

  PMID: 21163546 BACKGROUND

• Norenberg MD, Martinez-Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 1979 Feb 2;161(2):303-10. doi: 10.1016/0006-8993(79)90071-4.

  PMID: 31966 BACKGROUND

• Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94. doi: 10.1002/hep.21357.

  PMID: 17006913 BACKGROUND

• Donovan JP, Schafer DF, Shaw BW Jr, Sorrell MF. Cerebral oedema and increased intracranial pressure in chronic liver disease. Lancet. 1998 Mar 7;351(9104):719-21. doi: 10.1016/S0140-6736(97)07373-X.

  PMID: 9504517 BACKGROUND

• Laake JH, Takumi Y, Eidet J, Torgner IA, Roberg B, Kvamme E, Ottersen OP. Postembedding immunogold labelling reveals subcellular localization and pathway-specific enrichment of phosphate activated glutaminase in rat cerebellum. Neuroscience. 1999;88(4):1137-51. doi: 10.1016/s0306-4522(98)00298-x.

  PMID: 10336125 BACKGROUND

• Fischer JE, Rosen HM, Ebeid AM, James JH, Keane JM, Soeters PB. The effect of normalization of plasma amino acids on hepatic encephalopathy in man. Surgery. 1976 Jul;80(1):77-91.

  PMID: 818729 BACKGROUND

• Rossi-Fanelli F, Riggio O, Cangiano C, Cascino A, De Conciliis D, Merli M, Stortoni M, Giunchi G. Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study. Dig Dis Sci. 1982 Oct;27(10):929-35. doi: 10.1007/BF01316578.

  PMID: 6749458 BACKGROUND

• Cordoba J, Ventura-Cots M, Simon-Talero M, Amoros A, Pavesi M, Vilstrup H, Angeli P, Domenicali M, Gines P, Bernardi M, Arroyo V; CANONIC Study Investigators of EASL-CLIF Consortium. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol. 2014 Feb;60(2):275-81. doi: 10.1016/j.jhep.2013.10.004. Epub 2013 Oct 12.

  PMID: 24128414 BACKGROUND

• Dam G, Aamann L, Vistrup H, Gluud LL. The role of Branched Chain Amino Acids in the treatment of hepatic Encephalopathy. J Clin Exp Hepatol. 2018 Dec;8(4):448-451. doi: 10.1016/j.jceh.2018.06.004. Epub 2018 Jun 27.

  PMID: 30568347 BACKGROUND

• Gluud LL, Dam G, Les I, Cordoba J, Marchesini G, Borre M, Aagaard NK, Vilstrup H. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2015 Feb 25;(2):CD001939. doi: 10.1002/14651858.CD001939.pub2.

  PMID: 25715177 BACKGROUND

• Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology. 2009 Dec;50(6):2014-21. doi: 10.1002/hep.23216. No abstract available.

  PMID: 19787808 BACKGROUND

MeSH Terms

Conditions

Hepatic Encephalopathy; Acute-On-Chronic Liver Failure; Brain Edema

Interventions

Amino Acids; Lactulose

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Liver Failure, Acute

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind Placebo Controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSOCIATE PROFESSOR

Model Details: Prospective interventional cohort study

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: January 26, 2023
• Study Start: January 17, 2023
• Primary Completion: June 5, 2025
• Study Completion: June 5, 2025
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)