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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: Branched-chain amino acids (BCAA), enriched solution (Aminoleban) and L-ornithine L-aspartate (LOLA); Drug: Branched-chain amino acids (BCAA), enriched solution (Aminoleban)

Detailed Description

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

1. Mild lack of awareness
2. Lethargic
3. Somnolent but arousable
4. 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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11361
    • Ain-Shams University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2022
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 9, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 23, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Brain Diseases; Hepatic Encephalopathy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Excitatory Amino Acid Agonists; Excitatory Amino Acid Agents; N-Methylaspartate; Pharmaceutical Solutions
• Other Study ID Numbers: FMASU MS 556/ 2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No