BCAA vs. Rifaximin in Patients With Cirrhosis for Secondary Prophylaxis of HE
NCT Number: NCT06538077
Acronym: HERB
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Hepatic Encephalopathy|Decompensated Cirrhosis|Minimal Hepatic Encephalopathy
Interventions: DRUG: Oral Branched chain Amino acid|DRUG: Rifaximin 550 MG|DRUG: Lactulose|DRUG: Placebo for BCAA|DRUG: Placebo for Rifaximin 550mg
Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh
Collaborators: Indian Council of Medical Research
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 336
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2027-08
Locations: Dr. Madhumita Premkumar, Chandigarh, 160012, India|PGIMER, Chandigarh, 160012, India|Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

Summary:
Rationale

* Patients who recover from an episode of overt HE(OHE) are at risk of recurrent episodes of HE and persistent minimal hepatic encephalopathy, impacting their daily functioning and mental health.
* A multicentric pan-India team will evaluate the role of oral branched-chain amino acids (BCAA) vs Rifaximin as secondary prophylaxis following overt HE as compared with improvement in cognitive function.

Novelty:

* This study is intended to investigate the role of BCAA vs rifaximin as the ideal second-line therapy for HE management, recurrence, and overall health, including cognitive function, depression and anxiety.
* The head-to-head comparison of BCAA+lactulose+ pill-placebo vs rifaximin+ lactulose+ powder-placebo ensures minimization of bias and has adequate power to determine rates of recurrence,

Objectives:

* To assess the 1st breakthrough episode of HE during 6months in BCAA vs rifaximin groups as ideal secondary prophylaxis in HE. Methodology
* Double-blind placebo-controlled double-dummy randomized trial of BCAA supplementation vs rifaximin as the ideal second-line therapy in patients with cirrhosis who have recovered from an episode of OHE. Expected Outcome
* Ideal second line agent HE prophylaxis (rifaximin or BCAA) following 1st line lactulose is unclear in an Indian context where dysbiosis and sarcopenia are prevalent, and cost of therapy needs to be optimized.
* Optimal HE management prevents recurrence episodes of HE, and improves prognosis, neurocognitive function, and overall health-related quality of life(HRQOL).
* Creation of a management algorithm based deductive models incorporating etiology and severity of liver disease, cognitive performance, sarcopenia, and ammonia, and neuropsychiatric impact of using BCAA vs Rifaximin will be created.

Primary Outcome Measures: Number of breakthrough event of overt hepatic encephalopathy in BCAA vs rifaximin arm, Time to a breakthrough overt HE episode will be the duration (number of days) from time of first dose of study drug to the first breakthrough overt HE episode. The number of events of a first breakthrough overt HE episode during the treatment period will be assessed, 24 Weeks
Secondary Outcome Measures: Computerized Cognitive Test battery for Cognitive performance, A curated Computer based Cognitive test battery has been created for this protocol with a fixed set of tasks comprising Animal Naming Test, reaction times, digit span and number connection tests. This has been designed using the PEBL opensource language. Psychology Experiment Building Language. \[2019-03\] PEBL Version 2.1. The battery has been validated by us previously in patients with chronic hepatitis C infection., At Enrolment|Computerized Cognitive Test battery for Cognitive performance, Computerized Cognitive Test battery: A curated Computer based Cognitive test battery has been created for this protocol with a fixed set of tasks comprising Animal Naming Test, reaction times, digit span and number connection tests. This has been designed using the PEBL opensource language. Psychology Experiment Building Language. \[2019-03\] PEBL Version 2.1. The battery has been validated by us previously in patients with chronic hepatitis C infection., 30 days|Computerized Cognitive Test battery for Cognitive performance, Computerized Cognitive Test battery A curated Computer based Cognitive test battery has been created for this protocol with a fixed set of tasks comprising Animal Naming Test, reaction times, digit span and number connection tests. This has been designed using the PEBL opensource language. Psychology Experiment Building Language. \[2019-03\] PEBL Version 2.1. The battery has been validated by us previously in patients with chronic hepatitis C infection., 90 days|Psychiatric Assessment, Beck's Depression Inventory (BDI) test will be performed. The scoring is as follows 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression31-40: Severe depression 40: Extreme depression, 0 days|Psychiatric Assessment, Generalized anxiety disorder (GAD 7 score) will be performed. It has 7 questions. Using the threshold score of 10, the GAD-7 has a sensitivity of 89% and a specificity of 82% for GAD, 0 days|Psychiatric Assessment, Generalized anxiety disorder (GAD 7 score) test will be performed, 30 days|Psychiatric Assessment, Beck's Depression Inventory (BDI) test will be performed. The scoring is as follows 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression31-40: Severe depression 40: Extreme depression, 30 days|Psychiatric Assessment, Beck's Depression Inventory (BDI)test will be performed The scoring is as follows 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression31-40: Severe depression 40: Extreme depression, 90 days|Psychiatric Assessment, Generalized anxiety disorder (GAD 7 score) tests will be performed, 90 days|HRQOL will be performed by SF-36, Health related query of life will be performed., 0 days|HRQOL will be performed by SF-36, Health related query of life will be performed., 30 days|HRQOL will be performed by SF-36, Health related query of life will be performed., 90 days|Assessment of changes in ammonia, Estimation of ammonia by arterial fasting test/ capillary test will be performed, At enrolment|Assessment of changes in ammonia, Estimation of ammonia by arterial fasting test/ capillary test will be performed, 24 week|Assessment of changes in muscle health, Estimation of sarcopenia will be performed by muscle ultrasound by SARCUS., Baseline|Assessment of changes in muscle health, Estimation of sarcopenia by muscle ultrasound by SARCUS., 30 days|Assessment of changes in muscle health, Estimation of sarcopenia by muscle ultrasound by SARCUS., 90 days