Clinical trial NCT05700695: Intravenous BCAA for HE in ACLF (BCAA-HE-ACLF)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Encephalopathy
Acute-On-Chronic Liver Failure
Keywords: Hepatic Encephalopathy
Acute-On-Chronic Liver Failure
Neurological Dysfunction
Metabolomics
Systemic Inflammations
Branch Chain Amino Acid
bispectral index
Cerebral edema
Lactulose
Lead sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh
Sponsor class: OTHER
Collaborators: name: Amrita Institute of Medical Sciences & Research Center
name: Asian Institute of Gastroenterology, India
name: All India Institute of Medical Sciences, Bhubaneswar
name: Kalinga Institute of Medical Sciences, Bhubaneswar
First posted: 2023-01-26
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective interventional cohort study
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Survival
timeFrame: Day 28
Secondary outcomes:
measure: Reduction of arterial ammonia Level
timeFrame: Day 3
measure: Reduction of arterial ammonia Level
timeFrame: Day 7
measure: Assessment of cerebral edema
timeFrame: Discharge form Hospital and 3 month of episode of HE
measure: Prevention/reduction of cerebral edema based on optic nerve sheath diameter (ONSD)
timeFrame: 72 Hours
measure: Reduction of consciousness recovery time among survivors
timeFrame: Day 28
measure: Survival
timeFrame: Day 28
measure: Survival
timeFrame: Day 90
measure: Improvement of encephalopathy by one or more grade
timeFrame: Day 7
measure: Assessment of metabolomics following BCAA + Lactulose and Lactulose alone
timeFrame: Day 7
measure: 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.
timeFrame: Day 0
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Dr. Madhumita Premkumar
Study officials:
References:
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