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

February 8, 2007
February 8, 2007
October 2003
Not Provided
  • Improvement in HE grade.
  • deterioration in HE grade.
Same as current
No Changes Posted
  • Length of hospital stay
  • fasting ammonia level and
  • mortality rate
Same as current
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Hepatic Encephalopathy
Drug: L-Ornithine L-Aspartate
Not Provided
[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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
108
September 2004
Not Provided

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.
Both
14 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Pakistan
 
NCT00433368
OA001
Not Provided
Not Provided
Aga Khan University
Not Provided
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
Aga Khan University
February 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP