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| Name | Class |
|---|---|
| Amrita Institute of Medical Sciences & Research Center | OTHER |
| Asian Institute of Gastroenterology, India | OTHER |
| All India Institute of Medical Sciences, Bhubaneswar | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experiential Arm | Experimental | Drug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose |
|
| Comparator Arm | Active Comparator | Drug: Lactulose + Placebo of IV BCAA solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Branch Chain Amino Acid | Drug | Intravenous branched chain amino acids will be given for 3 days to patients in experimental arm |
|
| Measure | Description | Time Frame |
|---|---|---|
| Survival | Survival assessment will be made by recording all deaths | Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction of arterial ammonia Level | Level of ammonia will be measured by Point of care device | Day 3 |
| Reduction of arterial ammonia Level | Level of ammonia will be measured by Point of care device |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dr. Madhumita Premkumar | Chandigarh | Chandigarh | 160012 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21163546 | Background | 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. | |
| 31966 | Background |
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| ID | Term |
|---|---|
| D006501 | Hepatic Encephalopathy |
| D065290 | Acute-On-Chronic Liver Failure |
| D001929 | Brain Edema |
| ID | Term |
|---|---|
| D017093 | Liver Failure |
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000596 | Amino Acids |
| D007792 | Lactulose |
| ID | Term |
|---|---|
| D000602 | Amino Acids, Peptides, and Proteins |
| D004187 | Disaccharides |
| D009844 | Oligosaccharides |
| D011134 | Polysaccharides |
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| Kalinga Institute of Medical Sciences, Bhubaneswar |
| UNKNOWN |
Prospective interventional cohort study
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Double-blind Placebo Controlled
| Lactulose | Drug | Oral lactulose will be given to patients in both arms |
|
| Day 7 |
| 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 |
| Prevention/reduction of cerebral edema based on optic nerve sheath diameter (ONSD) | ONSD measurement will be done by Ultrasound | 72 Hours |
| Reduction of consciousness recovery time among survivors | Consciousness will be assessed by cognitive battery tests | Day 28 |
| Survival | Survival assessment will be done with recording all cause mortality | Day 28 |
| Survival | Survival assessment will be done with recording all cause mortality | Day 90 |
| Improvement of encephalopathy by one or more grade | Improvement in scoring of hepatic Encephalopathy | Day 7 |
| Assessment of metabolomics following BCAA + Lactulose and Lactulose alone | Metabolomics will be performed by LC/GC-MS | Day 7 |
| 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 |
| 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. |
| 17006913 | Background | Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94. doi: 10.1002/hep.21357. |
| 9504517 | 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. |
| 10336125 | 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. |
| 818729 | 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. |
| 6749458 | 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. |
| 24128414 | 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. |
| 30568347 | 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. |
| 25715177 | 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. |
| 19787808 | 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. |
| D001928 |
| Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D017114 | Liver Failure, Acute |
| D002241 |
| Carbohydrates |
| D000073893 | Sugars |