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

Primary Purpose

Hepatic Encephalopathy

Status
Completed
Phase
Phase 3
Locations
Pakistan
Study Type
Interventional
Intervention
L-Ornithine L-Aspartate
Sponsored by
Aga Khan University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Encephalopathy focused on measuring L-ornithine-L-aspartate,, porto-systemic encephalopathy,, hepatic encephalopathy,, liver cirrhosis,, mental state

Eligibility Criteria

14 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Aga Khan University Hospital

Outcomes

Primary Outcome Measures

Improvement in HE grade.
deterioration in HE grade.

Secondary Outcome Measures

Length of hospital stay
fasting ammonia level and
mortality rate

Full Information

First Posted
February 8, 2007
Last Updated
February 8, 2007
Sponsor
Aga Khan University
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1. Study Identification

Unique Protocol Identification Number
NCT00433368
Brief Title
Efficacy of L-Ornithine-L-Aspartate in Cirrhotics With Hepatic Encephalopathy
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 Type
Interventional

2. Study Status

Record Verification Date
February 2007
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
September 2004 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Aga Khan University

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Encephalopathy
Keywords
L-ornithine-L-aspartate,, porto-systemic encephalopathy,, hepatic encephalopathy,, liver cirrhosis,, mental state

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
108 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
L-Ornithine L-Aspartate
Primary Outcome Measure Information:
Title
Improvement in HE grade.
Title
deterioration in HE grade.
Secondary Outcome Measure Information:
Title
Length of hospital stay
Title
fasting ammonia level and
Title
mortality rate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wasim Jafri, MD; FRCP
Organizational Affiliation
Chairman Department of Medicine, Aga Khan University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Shahab Abid, MD
Organizational Affiliation
Associate Professor, Department of Medicine, Aga Khan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aga Khan University Hospital
City
Karachi
State/Province
Sind
ZIP/Postal Code
74800
Country
Pakistan

12. IPD Sharing Statement

Citations:
Citation
[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.
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Efficacy of L-Ornithine-L-Aspartate in Cirrhotics With Hepatic Encephalopathy

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