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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Hepatic Encephalopathy	Drug: L-ornithine-L-aspartate; Drug: Lactose	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	30 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, 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.
Study Start Date :	December 2009
Actual Primary Completion Date :	December 2011
Actual Study Completion Date :	December 2011

Arms and Interventions

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Arm	Intervention/treatment
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.

Outcome Measures

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Primary Outcome Measures :

1. Sustained improvement of at least one grade in mental state based on the West Haven criteria [ Time Frame: 48 hours ]

Secondary Outcome Measures :

1. Severity of hepatic encephalopathy assessed by the West Haven criteria [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ]
2. Severity of hepatic encephalopathy assessed by the Glasgow Coma Scale [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ]
3. Severity of hepatic encephalopathy assessed by the Clinical Hepatic Encephalopathy Staging Scale (CHESS) [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ]
4. Decrease in venous ammonia levels [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ]
5. Improvement in electroencephalographic tracing [ Time Frame: before intervention and 72 hours after intervention ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
First Posted:	January 1, 2010
Last Update Posted:	September 25, 2014
Last Verified:	September 2014

Keywords provided by Dr. Claudia Isabel Blanco Vela, Hospital Juarez de Mexico:

Encephalopathy; Cirrhosis

Additional relevant MeSH terms:

Brain Diseases; Hepatic Encephalopathy; Central Nervous System Diseases; Nervous System Diseases; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases	Brain Diseases, Metabolic; Metabolic Diseases; N-Methylaspartate; Excitatory Amino Acid Agonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs