Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

Hepatic Encephalopathy Clinical Trial

— BCAA-ACLF  

Official title:

Efficacy of Lactulose Plus Intravenous Branched Chain Amino Acids Versus Lactulose Alone in Patients of Acute on Chronic Liver Failure With Overt Hepatic Encephalopathy: A Prospective Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04238416
• Other study ID #: IEC-08/2019-1336
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2019
• Est. completion date: December 30, 2021

Study information

• Verified date: August 2022
• Source: Postgraduate Institute of Medical Education and Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• Brain Diseases
• End Stage Liver Disease
• Hepatic Encephalopathy
• Hepatic Insufficiency
• Liver Failure

Intervention

Drug:
• Branched chain amino acid
Intravenous branched chain amino acids will be given for 3 days to patients in experimental arm
• Lactulose
Oral lactulose will be given to patients in both arms

Locations

Country	Name	City	State
India	PGIMER	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

References & Publications (11)

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. — View Citation

Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94. Review. — View Citation

Cordoba J, Ventura-Cots M, Simón-Talero M, Amorós À, Pavesi M, Vilstrup H, Angeli P, Domenicali M, Ginés 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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Gluud LL, Dam G, Les I, Córdoba 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. Review. Update — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of Survival	All cause Mortality assessment	At day day 28
Primary	Improvement of encephalopathy by = 1 grade	Improvement in hepatic encephalopathy	72 hours
Secondary	Reduction in level of ammonia		48 and 72 hours
Secondary	Reduction of consciousness recovery time among survivors		30 days
Secondary	Prolongation of time to death among non-survivors		30 days
Secondary	Prevention/reduction of cerebral edema based on optic nerve sheath diameter		72 hours