Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

NCT ID: NCT04238416

Last Updated: 2022-08-16

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

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-01

Study Completion Date

2021-12-30

Brief Summary

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This study analyses the effect of intravenous branched chain amino acids (BCAA) on overt HE in patients with ACLF. The investigators plan to study the efficacy of combining intravenous BCAA with lactulose versus lactulose alone in the medical management of overt HE in patients with ACLF and its impact on overall survival and improvement in grade of HE.

Detailed Description

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Acute on chronic liver failure (ACLF) is a distinct clinical entity in the spectrum of chronic liver disease associated with high short term mortality. Hepatic encephalopathy (HE) is commonly seen in patients with ACLF and its treatment mainly involves non-absorbable disaccharides (lactulose/lactitol).Treatment of HE in ACLF is based on extrapolation of data available from cirrhotic patients. No studies have compared different treatment options for HE in 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

NONE

Study Groups

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IV BCAA + Lactulose

IV Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose

Group Type EXPERIMENTAL

Branched 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

Lactulose alone

Oral Lactulose alone

Group Type ACTIVE_COMPARATOR

Lactulose

Intervention Type DRUG

Oral lactulose will be given to patients in both arms

Interventions

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Branched 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 aetiology with HE ≥grade 2 as per West-Haven Criteria or Hepatic encephalopathy scoring algorithm (HESA)

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

As the study was carried out during the peak of the COVID-19, patients who developed COVID-19 after randomization were excluded from the analysis as they were shifted to dedicated COVID-19 ICU's.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role lead

Responsible Party

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Madhumita Premkumar

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Madhumita Premkumar, MD, DM

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Locations

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PGIMER

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)

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)

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)

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, Dolinska M, Hilgier W, Lipkowski AW, Nowacki J. Modulation of glutamine uptake and phosphate-activated glutaminase activity in rat brain mitochondria by amino acids and their synthetic analogues. Neurochem Int. 2000 Apr;36(4-5):341-7. doi: 10.1016/s0197-0186(99)00142-4.

Reference Type BACKGROUND
PMID: 10733001 (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)

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)

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 RESULT
PMID: 818729 (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 RESULT
PMID: 30568347 (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 RESULT
PMID: 6749458 (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 RESULT
PMID: 25715177 (View on PubMed)

Mehtani R, Premkumar M, Garg S, Kajal K, Kulkarni AV, Duseja AK, Dhiman RK, De A, Verma N, Taneja S, Rathi S, Singh V, Chakma J, Soni SL, Kakkar A, Kapila AT, Ahuja CK, Divyaveer S, Praharaj D. Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial. J Clin Exp Hepatol. 2023 Nov-Dec;13(6):977-988. doi: 10.1016/j.jceh.2023.05.015. Epub 2023 Jun 1.

Reference Type DERIVED
PMID: 37975059 (View on PubMed)

Other Identifiers

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IEC-08/2019-1336

Identifier Type: -

Identifier Source: org_study_id

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