Efficacy of L-Ornithine L-Aspartate in Acute Hepatic Encephalopathy.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dr. Claudia Isabel Blanco Vela, Hospital Juarez de Mexico
ClinicalTrials.gov Identifier:
NCT01041755
First received: December 31, 2009
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

Hepatic encephalopathy is caused by the effects on the brain of substances that under normal circumstances are efficiently metabolized in the liver. The hyperammonemia is the main factor responsible for the development of hepatic encephalopathy. In patients with cirrhosis, the reduction in hepatocellular function and generation of portosystemic shunts contribute to increase serum ammonium. The current therapeutic approaches, are aimed at reducing blood ammonium levels.

Administration of the non-absorbable disaccharides, have become standard treatment of hepatic encephalopathy.There are no adequate clinical trials comparing the efficacy of L-Ornithine-L-Aspartate (LOLA) infusion against lactose enemas in the treatment of acute hepatic encephalopathy.


Condition Intervention Phase
Hepatic Encephalopathy
Drug: L-ornithine-L-aspartate
Drug: Lactose
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Infusion of L-Ornithine L-aspart is as Effective as Nonabsorbable Disaccharides in the Management of Acute Hepatic Encephalopathy.

Resource links provided by NLM:


Further study details as provided by Centro Regional para el Estudio de las Enfermedades Digestivas:

Primary Outcome Measures:
  • Sustained improvement of at least one grade in mental state based on the West Haven criteria [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Severity of hepatic encephalopathy assessed by the West Haven criteria [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ] [ Designated as safety issue: No ]
  • Severity of hepatic encephalopathy assessed by the Glasgow Coma Scale [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ] [ Designated as safety issue: No ]
  • Severity of hepatic encephalopathy assessed by the Clinical Hepatic Encephalopathy Staging Scale (CHESS) [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ] [ Designated as safety issue: No ]
  • Decrease in venous ammonia levels [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ] [ Designated as safety issue: No ]
  • Improvement in electroencephalographic tracing [ Time Frame: before intervention and 72 hours after intervention ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: December 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intravenous infusion of L- Ornithine L- Aspartate
a) 20 g L-ornithine-L-aspartate
Drug: L-ornithine-L-aspartate
a) Intravenous infusion of 20 g L-ornithine-L-aspartate (4 ampules of 10 mL each) in 250 mL sodium chloride solution administered daily in 4 hours for 3 consecutive days, plus the placebo b) Water enemas, 1000 mL of water and given as retention enema every 12 hours for 3 consecutive days.
Other Name: LOLA
Active Comparator: Lactose enemas
b) 20% Lactose enemas
Drug: Lactose
a) 20% Lactose enemas, 200 g Lactose diluted with 700 mL of water and given as retention enema every 12 hours for 3 consecutive days, plus intravenous placebo b)250 mL sodium chloride solution, infusion for 4 hours for 3 consecutive days.
Other Name: Lactose

Detailed Description:

The main impact of hepatic encephalopathy in patients with cirrhosis is not related to costs, but its association with decreased survival and quality of life and should therefore clearly established the effectiveness of therapeutic interventions used in this disorder.

At the end of the nineteenth century to the ammonium was identified as the main agent responsible for the development of the syndrome of hepatic encephalopathy. Since then, reduced nitrogen compounds from the intestine are considered the main therapeutic measure. On this conceptual base, nonabsorbable disaccharides are the first line therapy in hepatic encephalopathy.

Current knowledge indicates that other organs such as muscle, brain and kidney are involved in the generation of ammonium, which has set the pace for the development of new treatments, able to act systemically in metabolism and elimination of ammonia . L-ornithine L-aspartate (LOLA) lowers ammonium concentrations in animal and humans models with hyperammonemia. There are no adequate clinical trials comparing the efficacy of LOLA infusion against lactose enemas in the treatment of acute hepatic encephalopathy.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with cirrhosis of any etiology, diagnosed by ultrasound,clinical and / or histologic criteria
  • Patients over 18 years and under 75
  • Patients with hepatic encephalopathy grade 3-4 according to the criteria of West Haven
  • Patients with hyperammonemia >35 µmol/l

Exclusion Criteria:

  • Evidence of other neurological or psychiatric abnormality
  • Renal failure (serum creatinine greater than 3 mg / dL)
  • Use of drugs affecting the central nervous system
  • Withdrawal Syndrome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01041755

Locations
Mexico
Hospital Universitario "José Eleuterio González"
Monterrey, Nuevo León, Mexico, 64460
Sponsors and Collaborators
Centro Regional para el Estudio de las Enfermedades Digestivas
Investigators
Study Director: Francisco J Bosques, MD, PhD Centro Regional para el Estudio de las Enfermedades Digestivas
Principal Investigator: Claudia Isabel Blanco Vela, MD Hospital Juárez de México
  More Information

No publications provided

Responsible Party: Dr. Claudia Isabel Blanco Vela, MD, Hospital Juarez de Mexico
ClinicalTrials.gov Identifier: NCT01041755     History of Changes
Other Study ID Numbers: MI09-002
Study First Received: December 31, 2009
Last Updated: September 22, 2014
Health Authority: United States: Institutional Review Board
Mexico: Ethics Committee

Keywords provided by Centro Regional para el Estudio de las Enfermedades Digestivas:
Encephalopathy
Cirrhosis

Additional relevant MeSH terms:
Brain Diseases
Hepatic Encephalopathy
Brain Diseases, Metabolic
Central Nervous System Diseases
Digestive System Diseases
Hepatic Insufficiency
Liver Diseases
Liver Failure
Metabolic Diseases
Nervous System Diseases
N-Methylaspartate
Excitatory Amino Acid Agents
Excitatory Amino Acid Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014