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L-ornithine L-aspartate in Overt Hepatic Encephalopathy (HEAL)

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ClinicalTrials.gov Identifier: NCT01722578
Recruitment Status : Completed
First Posted : November 7, 2012
Last Update Posted : February 8, 2017
Sponsor:
Information provided by (Responsible Party):
Prof. Sandeep S Sidhu, Dayanand Medical College and Hospital

Brief Summary:
Hepatic encephalopathy (HE) is a potentially reversible functional disorder of the brain with neurological and psychiatric symptoms. HE occurs in up to 70% of patients with cirrhosis at some time during the course of disease. The chief neurotoxin implicated in the development of HE is ammonia. An important aim of treatment of HE is the reduction of the ammonia in the body by lowering the amount of ammonia produced and increasing its detoxification. Enteric production of ammonia can be decreased by non-absorbable disaccharides such as lactulose and antibiotics such as rifaximin. L-ornithine- L-aspartate (LOLA), the salt of the natural amino acids ornithine and aspartate acts through the mechanism of substrate activation to detoxify ammonia. In clinical trials, LOLA has shown a statistically significant effect with respect to reduction in HE grade, reduction of blood ammonia concentration and positive effects on psychomotor function in patients of cirrhosis with minimal HE and overt chronic Grade I HE, as compared to placebo. However, there is lack of data on the efficacy of LOLA in patients with overt acute hepatic encephalopathy which is one of the major causes of hospital admissions and resource utilization in decompensated cirrhotics. Each admission for HE causes a major financial loss to the family and financial burden on the society. Any drug which decreases the hospital stay by rapidly improving HE, will clearly lead to decreased hospital costs to the individual and the society as a whole. Hence, such a trial is a national priority. The investigators hypothesize that LOLA, if added to the standard treatment of overt acute HE (i.e lactulose), may lead to a faster recovery and decrease in hospital stay of these patients. In this prospective, randomized, placebo controlled trial, the investigators aim to evaluate the efficacy of intravenous L-ornithine, L-aspartate in reversal of overt acute hepatic encephalopathy in patients with liver cirrhosis.

Condition or disease Intervention/treatment Phase
Cirrhosis of Liver Hepatic Encephalopathy Drug: L-ornithine L-aspartate Drug: Placebo Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Intravenous 'L-ornithine L-aspartate' in Reversal of Overt Acute Hepatic Encephalopathy in Patients With Liver Cirrhosis: a Prospective, Randomized, Double-blind, Placebo Controlled Trial
Study Start Date : December 2013
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017


Arm Intervention/treatment
Experimental: L-ornithine L-aspartate
L-ornithine L-aspartate (6 ampules, each ampule containing 5 grams of the drug in 10 ml solution) to be diluted in 440 ml of Dextrose 5% (to make a total of 500 ml of solution), as intravenous infusion at the rate of 21 ml/hour, over 24 hours, for 5 days
Drug: L-ornithine L-aspartate
L-ornithine L-aspartate (6 ampules, each ampule containing 5 grams of the drug in 10 ml solution) to be diluted in 440 ml of Dextrose 5% (to make a total of 500 ml of solution), as intravenous infusion at the rate of 21 ml/hour, over 24 hours, for 5 days
Other Name: Hepamerz

Placebo Comparator: Placebo (sterile water)
Placebo (sterile water, 6 ampuoles of 10 ml each) diluted in 440 ml of Dextrose 5%, as intravenous infusion at the rate of 21 ml/hour, over 24 hours, for 5 days
Drug: Placebo
Placebo (sterile water, 60 ml) diluted in 440 ml of Dextrose 5%, as intravenous infusion at the rate of 21 ml/hour, over 24 hours, for 5 days




Primary Outcome Measures :
  1. Mental state grade [ Time Frame: 5 days ]
    Mental state grade according to West Haven criteria for Hepatic encephalopathy


Secondary Outcome Measures :
  1. Blood Ammonia levels [ Time Frame: 5 days ]
    Change in blood ammonia levels will be measured at baseline and after 5 days of treatment

  2. Mortality [ Time Frame: 4 weeks ]
    Mortality rate in the two groups at 4 weeks will be compared

  3. Length of Hospital stay [ Time Frame: 4 weeks ]
    The total length of hospital stay (number of days) in each group will be compared.

  4. Serum Cytokine levels [ Time Frame: 5 days ]
    Change in serum cytokine levels (Interleukin-1, Interleukin-6, Interleukin-10 and TNF-alpha will be measured at baseline and after 5 days of treatment.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hepatic cirrhosis based on clinical, biochemical, radiological and/or histological data
  • Patients with overt acute grade 2, 3 and 4 HE, according to the West Haven criteria, with or without precipitating factors.
  • Age of patient 18-70 years

Exclusion Criteria:

  • Patients who are terminally ill
  • Acute on chronic liver failure
  • Hepatocellular carcinoma
  • Wilson's disease as the etiological factor of liver disease
  • Advanced cardiac or pulmonary disease
  • Presence of underlying chronic renal failure
  • Neuro-degenerative disease or major psychiatric illness
  • Patients on sedatives or antidepressants
  • Pregnancy or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01722578


Locations
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India
Department of Gastroenterology, D.M.C. and Hospital
Ludhiana, Punjab, India, 141001
G.B. Pant Hospital
New Delhi, India, 110002
Sponsors and Collaborators
Dayanand Medical College and Hospital
Investigators
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Principal Investigator: Sandeep S Sidhu, MD,DM Professor, Dept of Gastroenterology, DMC and Hospital, Ludhiana, India
Principal Investigator: Omesh Goyal, MD, DM Assistant Professor, Dept of Gastroenterology, DMC and Hospital, Ludhiana, India
Principal Investigator: B C Sharma, D.M. Professor, Dept of Gastroenterology, G.B. Pant Hospital, New Delhi

Publications:

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Responsible Party: Prof. Sandeep S Sidhu, Professor, Dayanand Medical College and Hospital
ClinicalTrials.gov Identifier: NCT01722578     History of Changes
Other Study ID Numbers: HEAL-123
First Posted: November 7, 2012    Key Record Dates
Last Update Posted: February 8, 2017
Last Verified: February 2017

Keywords provided by Prof. Sandeep S Sidhu, Dayanand Medical College and Hospital:
Cirrhosis
Encephalopathy
L-ornithine L-aspartate

Additional relevant MeSH terms:
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Fibrosis
Liver Cirrhosis
Brain Diseases
Hepatic Encephalopathy
Pathologic Processes
Liver Diseases
Digestive System Diseases
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
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