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

Hepatic Encephalopathy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00433368
• Other study ID #: OA001
• Status: Completed
• Phase: Phase 3
• First received: February 8, 2007
• Last updated: February 8, 2007
• Start date: October 2003
• Est. completion date: September 2004

Study information

• Verified date: February 2007
• Source: Aga Khan University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Pakistan: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: September 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy

Intervention

Drug:
• L-Ornithine L-Aspartate

Locations

Country	Name	City	State
Pakistan	Aga Khan University Hospital	Karachi	Sind

Sponsors (1)

Lead Sponsor	Collaborator
Aga Khan University

Country where clinical trial is conducted

Pakistan, 

References & Publications (1)

[1] ] STAEDT U, LEWELING H, GLADISCH R, KORTSIK C, HAGMULLER E, HOLM E. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J Hepatol 1993

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in HE grade.
Primary	deterioration in HE grade.
Secondary	Length of hospital stay
Secondary	fasting ammonia level and
Secondary	mortality rate