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

This study has been completed.
Sponsor:
Information provided by:
Aga Khan University
ClinicalTrials.gov Identifier:
NCT00433368
First received: February 8, 2007
Last updated: NA
Last verified: February 2007
History: No changes posted
  Purpose

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


Condition Intervention Phase
Hepatic Encephalopathy
Drug: L-Ornithine L-Aspartate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by Aga Khan University:

Primary Outcome Measures:
  • Improvement in HE grade.
  • deterioration in HE grade.

Secondary Outcome Measures:
  • Length of hospital stay
  • fasting ammonia level and
  • mortality rate

Estimated Enrollment: 108
Study Start Date: October 2003
Estimated Study Completion Date: September 2004
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.

  Eligibility

Ages Eligible for Study:   14 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00433368

Locations
Pakistan
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
  More Information

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.

ClinicalTrials.gov Identifier: NCT00433368     History of Changes
Other Study ID Numbers: OA001
Study First Received: February 8, 2007
Last Updated: February 8, 2007
Health Authority: Pakistan: Research Ethics Committee

Keywords provided by Aga Khan University:
L-ornithine-L-aspartate,
porto-systemic encephalopathy,
hepatic encephalopathy,
liver cirrhosis,
mental state

Additional relevant MeSH terms:
Hepatic Encephalopathy
Brain Damage, Chronic
Delirium
Encephalitis
Neurotoxicity Syndromes
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolic Diseases
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Central Nervous System Viral Diseases
Virus Diseases
Central Nervous System Infections
Poisoning
Substance-Related Disorders
N-Methylaspartate
Excitatory Amino Acid Agonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014