Hepatic Encephalopathy Clinical Trial
Official title:
Intravenous Branched-chain Amino Acids for Overt Hepatic Encephalopathy in Patients With Acute on Chronic Liver Failure - A Multi-centric Double-blind Randomized Controlled Trial
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.
Status | Recruiting |
Enrollment | 226 |
Est. completion date | April 25, 2025 |
Est. primary completion date | April 25, 2025 |
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 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. |
Country | Name | City | State |
---|---|---|---|
India | Dr. Madhumita Premkumar | Chandigarh |
Lead Sponsor | Collaborator |
---|---|
Post Graduate Institute of Medical Education and Research, Chandigarh | All India Institute of Medical Sciences, Bhubaneswar, Amrita Institute of Medical Sciences & Research Center, Asian Institute of Gastroenterology, India, Kalinga Institute of Medical Sciences, Bhubaneswar |
India,
Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94. doi: 10.1002/hep.21357. — View Citation
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. — View Citation
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. — 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. — 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. doi: 10.1016/S0140-6736(97)07373-X. — 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, 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. — 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. doi: 10.1016/s0306-4522(98)00298-x. — 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. doi: 10.1016/0006-8993(79)90071-4. — 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. doi: 10.1007/BF01316578. — 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
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Survival | Survival assessment will be made by recording all deaths | Day 28 | |
Secondary | Reduction of arterial ammonia Level | Level of ammonia will be measured by Point of care device | Day 3 | |
Secondary | Reduction of arterial ammonia Level | Level of ammonia will be measured by Point of care device | Day 7 | |
Secondary | Assessment of cerebral edema | Cerebral edema will be assessed by Magnetic Resonance Imaging+ Magnetic Resonance Spectroscopy | Discharge form Hospital and 3 month of episode of HE | |
Secondary | Prevention/reduction of cerebral edema based on optic nerve sheath diameter (ONSD) | ONSD measurement will be done by Ultrasound | 72 Hours | |
Secondary | Reduction of consciousness recovery time among survivors | Consciousness will be assessed by cognitive battery tests | Day 28 | |
Secondary | Survival | Survival assessment will be done with recording all cause mortality | Day 28 | |
Secondary | Survival | Survival assessment will be done with recording all cause mortality | Day 90 | |
Secondary | Improvement of encephalopathy by one or more grade | Improvement in scoring of hepatic Encephalopathy | Day 7 | |
Secondary | Assessment of metabolomics following BCAA + Lactulose and Lactulose alone | Metabolomics will be performed by LC/GC-MS | Day 7 | |
Secondary | Dynamic Assessment of systemic inflammation (Cytokines: IL-1b, IL-6, INF-g, TNF-a, IL-15, IL-17, IL-18) at presentation and after Specific management. | Systemic inflammation will be accessed by Cytometric Bead Array | Day 0 |
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