Efficacy of L-Ornithine-L-Aspartate in Cirrhotics With Hepatic Encephalopathy

Sponsor

Aga Khan University (Other)

Overall Status

Completed

CT.gov ID

NCT00433368

Collaborator

(none)

108

Enrollment

Location

Duration (Months)

9.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether L-Ornithine L-Aspartate is effective for the improvement of Overt Hepatic Encephalopathy.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy	Drug: L-Ornithine L-Aspartate	Phase 3

Detailed Description

There is no effective treatment available for hepatic encephalopathy at the moment; therefore we aimed to check the efficacy and safety of L-ornithine L-aspartate(LOLA). It provides critical substrates for ureagenesis and glutamine synthesis, the two primary mechanisms by which the body rids itself of excess ammonia. Ornithine is a specific activator of ornithine carbamyl transferase and carbamylphosphate synthetase, and, in addition, is a substrate for ureagenesis. These reactions are carried out mainly in the periportal portion of the hepatic lobules. Aspartate and ornithine, after conversion to alfa-ketoglutarate, are substrates for glutamine synthesis, which is performed exclusively by a small population of perivenous hepatocytes, the so-called perivenous scavenger cells. The ammonia lowering effect resulting from the stimulation of these two basic mechanisms of ammonia detoxification has been studied in animals and was confirmed in humans in clinical trials.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

Efficacy of a Three Days' Infusion of L-Ornithine-L-Aspartate as an Adjuvant Therapy in Cirrhotic Patients With Overt Hepatic Encephalopathy: A Placebo Controlled Study

Study Start Date :

Oct 1, 2003

Study Completion Date :

Sep 1, 2004

Outcome Measures

Primary Outcome Measures

Improvement in HE grade. []
deterioration in HE grade. []

Secondary Outcome Measures

Length of hospital stay []
fasting ammonia level and []
mortality rate []

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cirrhosis, diagnosed on the basis of clinical findings, sonographic, and/or histologic basis,
Patients >14 years, with HE grades 1 to 4 according to West Haven Criteria,
Hyperammonemia (fasting venous blood ammonia level >60 µmol/l), and
Patients with a single reversible precipitating factor of HE such as constipation, hypokalemia, urinary tract infection, respiratory tract infection, spontaneous bacterial peritonitis (SBP), dehydration, or none.

Exclusion Criteria:

hepatocellular carcinoma,
severe septicemia,
active gastrointestinal bleeding,
hepatorenal syndrome,
acute superimposed liver injury,
advanced cardiac or pulmonary disease and end stage renal failure,
patients with minimal HE
patients taking sedatives, antidepressants, or benzodiazepines and
patients with chronic HE on metronidazole or lactulose prior to admission.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aga Khan University Hospital	Karachi	Sind	Pakistan	74800

Sponsors and Collaborators

Aga Khan University

Investigators

Study Chair: Wasim Jafri, MD; FRCP, Chairman Department of Medicine, Aga Khan University Hospital
Principal Investigator: Shahab Abid, MD, Associate Professor, Department of Medicine, Aga Khan University