Efficacy of L-Ornithine L-Aspartate (LOLA) as an Adjunct to Branched Chain Amino Acids (BCAA) Enriched Solutions on Clinical Outcomes in ICU Patients With Hepatic Encephalopathy

Study Overview
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Brief Summary
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One of the most significant goals of hepatic encephalopathy (HE) treatment is to reduce ammonia levels by lowering its synthesis and enhancing its detoxification which can be achieved by using non-absorbable disaccharides, antibiotics, branched-chain amino acids (BCAA), L-ornithine L-aspartate (LOLA), and probiotics. LOLA decreases ammonia, therefore, it is presumed to decrease agitated delirium in HE patients and thus decrease their need for other sedatives. On the other hand, BCAA improve mental function in HE patients by increasing the detoxification of ammonia in muscles.

Detailed Description
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The most often utilized criteria for grading HE are the West Haven criteria (WHC). This grading distinguishes four levels of clinically evident hepatic encephalopathy. West Haven criteria (WHC): [R] Stage Consciousness 0. Normal Mild lack of awareness Lethargic Somnolent but arousable Coma REFERENCES: Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy-definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congress of Gastroenterology, Vienna, 1998. Hepatology 2002; 35: 716-21.

Official Title
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Efficacy of L-Ornithine L-Aspartate (LOLA) as an Adjunct to Branched Chain Amino Acids (BCAA) Enriched Solutions on Clinical Outcomes in ICU Patients With Hepatic Encephalopathy: a Randomized Controlled Trial

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: Branched-chain amino acids (BCAA), enriched solution (Aminoleban) and L-ornithine L-aspartate (LOLA)
* Drug: Branched-chain amino acids (BCAA), enriched solution (Aminoleban)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with Liver cirrhosis based on clinical, biochemical, radiological and/or histopathology. Patients having overt HE, West Haven criteria (WHC) grade III-IV. Exclusion Criteria: Age < 21 years. Inability to obtain an informed consent from the first degree relative and/or legally authorized representative. Advanced cardiac or pulmonary disease. Presence of underlying chronic renal failure (serum creatinine > 3 mg/dL). Neurodegenerative disease (including head injury and drug intoxication). Major psychiatric illness. Use of sedatives or antidepressants. Pregnancy or breast-feeding . Hepatocellular carcinoma. Acute on top of chronic liver failure.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 (Treatment group)<br> | Drug: Branched-chain amino acids (BCAA), enriched solution (Aminoleban) and L-ornithine L-aspartate (LOLA)<br>* patients will receive branched-chain amino acids (BCAA), enriched solution (Aminoleban) and L-ornithine L-aspartate (LOLA)<br>|
| Active Comparator: Group 2 (Control group)<br> | Drug: Branched-chain amino acids (BCAA), enriched solution (Aminoleban)<br>* patients will receive BCAA enriched solution (Aminoleban)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reversal of Hepatic encephalopathy or change of Hepatic encephalopathy by two grades (according to West Havens Criteria) | Reversal of Hepatic encephalopathy or change of Hepatic encephalopathy by two grades (according to West Havens Criteria) | 5 days of treatment |