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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: L-Ornithine L-Aspartate

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 Type: Interventional
• Enrollment: 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • Sind
    • Karachi, Sind, Pakistan, 74800
      • Aga Khan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Improvement in HE grade.
deterioration in HE grade.

Secondary Outcome Measures

Outcome Measure
Length of hospital stay
fasting ammonia level and
mortality rate

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• [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;19(3): 424-430. [2] KIRCHEIS G, NILIUS R, HELD C, BERNDT H, BUCHNER M, GÖRTELMEYER R, et al. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology 1997;25(6):1351-1360. [3] FEHÉR J, LÁNG I, GÓGL A, VARGA L, TOMPOS G, PRÓNAI L. Effect of ornithine-aspartate infusion on elevated serum ammonia concentration in cirrhotic patients - results of a randomized, placebo-controlled double-blind multicentre trial. Med Sci Monit 1997; 3(5):669-673. [4] KIRCHEIS G, WETTSTEIN M, VOM DAHL S, HÄUSSINGER D. Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy. Met Brain Dis 2002;17(4): 453-462. [5] REES CJ, OPPONG K, AL MARDINI H, HUDSON M, RECORD CO. Effect of L- ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial. Gut 2000; 47(4): 571-574.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Study Completion: September 1, 2004

Study Registration Dates

• First Submitted: February 8, 2007
• First Submitted That Met QC Criteria: February 8, 2007
• First Posted (Estimate): February 9, 2007

Study Record Updates

• Last Update Posted (Estimate): February 9, 2007
• Last Update Submitted That Met QC Criteria: February 8, 2007
• Last Verified: February 1, 2007

More Information

Terms related to this study

• Keywords: L-ornithine-L-aspartate,; porto-systemic encephalopathy,; hepatic encephalopathy,; liver cirrhosis,; mental state
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Agents; Excitatory Amino Acid Agonists; N-Methylaspartate
• Other Study ID Numbers: OA001