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

NCT ID: NCT05700695

Last Updated: 2025-06-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-17

Study Completion Date

2025-06-05

Brief Summary

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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.

Detailed Description

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Treatment of HE in ACLF is based on extrapolation of data available from cirrhotic patients with HE. The mainstay of treatment remains Lactulose. Rifaximin is added on to therapy who have a breakthrough episode of HE on lactulose. BCAA is used as an add-on therapy if patients have minimal/covert encephalopathy, are protein intolerant or have recurrent HE. No studies are available assessing the adjuvant effect of intravenous BCAA on ammonia reduction in HE in patients with ACLF. So, this study has been designed to analyze the effect of intravenous BCAA on hepatic encephalopathy in patients with ACLF. This study will also analyze the systemic and neuronal inflammation, metabolomics, and cerebral edema under the effect of intravenous BCAA in HE patients with ACLF.

Conditions

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Hepatic Encephalopathy Acute-On-Chronic Liver Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective interventional cohort study
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blind Placebo Controlled

Study Groups

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Experiential Arm

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

Group Type EXPERIMENTAL

Branch Chain Amino Acid

Intervention Type DRUG

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

Lactulose

Intervention Type DRUG

Oral lactulose will be given to patients in both arms

Comparator Arm

Drug: Lactulose + Placebo of IV BCAA solution

Group Type ACTIVE_COMPARATOR

Lactulose

Intervention Type DRUG

Oral lactulose will be given to patients in both arms

Interventions

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Branch Chain Amino Acid

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

Intervention Type DRUG

Lactulose

Oral lactulose will be given to patients in both arms

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amrita Institute of Medical Sciences & Research Center

OTHER

Sponsor Role collaborator

Asian Institute of Gastroenterology, India

OTHER

Sponsor Role collaborator

All India Institute of Medical Sciences, Bhubaneswar

OTHER

Sponsor Role collaborator

Kalinga Institute of Medical Sciences, Bhubaneswar

UNKNOWN

Sponsor Role collaborator

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role lead

Responsible Party

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Madhumita Premkumar

ASSOCIATE PROFESSOR

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Dr. Madhumita Premkumar

Chandigarh, Chandigarh, India

Site Status

Countries

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India

References

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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.

Reference Type BACKGROUND
PMID: 21163546 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31966 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 17006913 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9504517 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10336125 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 818729 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6749458 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24128414 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30568347 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25715177 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19787808 (View on PubMed)

Other Identifiers

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IEC/04/2022-2385

Identifier Type: -

Identifier Source: org_study_id

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