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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00433368
Recruitment Status : Completed
First Posted : February 9, 2007
Last Update Posted : February 9, 2007
Information provided by:
Aga Khan University

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.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 108 participants
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 : October 2003
Study Completion Date : September 2004

Primary Outcome Measures :
  1. Improvement in HE grade.
  2. deterioration in HE grade.

Secondary Outcome Measures :
  1. Length of hospital stay
  2. fasting ammonia level and
  3. mortality rate

Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00433368

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Aga Khan University Hospital
Karachi, Sind, Pakistan, 74800
Sponsors and Collaborators
Aga Khan University
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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 of Results:
[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.

Layout table for additonal information Identifier: NCT00433368    
Other Study ID Numbers: OA001
First Posted: February 9, 2007    Key Record Dates
Last Update Posted: February 9, 2007
Last Verified: February 2007
Keywords provided by Aga Khan University:
porto-systemic encephalopathy,
hepatic encephalopathy,
liver cirrhosis,
mental state
Additional relevant MeSH terms:
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Hepatic Encephalopathy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Metabolic Diseases
Excitatory Amino Acid Agonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs