Nitazoxanide Plus Lactulose Versus Lactulose Alone Treatment of Hepatic Encephalopathy

August 16, 2017 updated by: Sherief Abd-Elsalam

A Randomized, Double-blind, Controlled Trial Comparing Nitazoxanide Plus Lactulose With Lactulose Alone Treatment of Overt Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction. It is characterized by cognitive and motor deficits of varying severity.

Treatment options include lactulose administered orally or by nasogastric tube or enema, non-absorbable antibiotics, and protein-restricted diets.

Nitazoxanide is an oral agent indicated for the treatment of infectious diarrhea caused by Crytpsporidiumparvum and Giardia lamblia. Basu and colleagues presented a pilot prospective study at the 2008 American Association for the Study of Liver Diseases meeting showing clinical improvement in HE among cirrhotic patients who received nitazoxanide and lactulose.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction. It is characterized by cognitive and motor deficits of varying severity.

Hepatic encephalopathy is caused by accumulation of nitrogenous substances, primarily ammonia, in the blood. In advanced stages it is referred to as hepatic coma which may be preceded by seizures. The treatment goal is to reduce nitrogen load from the GI tract and to improve central nervous system (CNS) status.

Treatment options include lactulose administered orally or by nasogastric tube or enema, non-absorbable antibiotics, and protein-restricted diets.

Lactulose is nonabsorbable disaccharides that are currently used as first line agents for the treatment of HE. Its action is thought to beconversion to lactic acid and acetic acid resulting in acidification of the gut lumen. This favors conversion of ammonia (NH3) to ammonium (NH4+), which is relatively membrane impermeable, and inhibits ammoniagenic coliform bacteria.

Nitazoxanide is an oral agent indicated for the treatment of infectious diarrhea caused by Crytpsporidiumparvum and Giardia lamblia. Basu and colleagues presented a pilot prospective study at the 2008 American Association for the Study of Liver Diseases meeting showing clinical improvement in HE among cirrhotic patients who received nitazoxanide and lactulose.

Mantry and colleagues showed that the number of hospitalizations and the duration of hospital stays were shortened for patients receiving combination therapy compared with those receiving lactulose monotherapy.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
    • Elgharbia
      • Tanta, Elgharbia, Egypt
        • Recruiting
        • Tanta university - faculty of medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Age 18-70 years

Cirrhosis, defined by a combination of any of the following:

  • Laboratory findings
  • Endoscopic results
  • Ultrasound
  • Histology Overt hepatic encephalopathy

Exclusion Criteria:

  • • Creatinine>1.5 mg/dl

    • Alcohol use within prior 4 weeks
    • Non-hepatic metabolic encephalopathy
    • Hepatocellular carcinoma
    • Degenerative CNS disease
    • Any significant psychiatric illness or other medical comorbidity

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: lactulose plus nitazoxanide
  • Nitazoxanide dosing: 500 mg tablets twice daily
  • Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
Drug: Nitazoxanide
• Nitazoxanide dosing: 500 mg tablets twice daily
Other Names:
  • Alenia, Nitclean, Parazoxanide
Drug: Lactulose
• Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
Other Names:
  • Laxolac, Duphlac
Active Comparator: Lactulose alone
Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
Drug: Lactulose
• Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
Other Names:
  • Laxolac, Duphlac

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of patients with total reversal of hepatic encephalopathy
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sherief Abd-Elsalam

Collaborators

Tanta University

Investigators

  • Principal Investigator: Asem Elfert, Prof, hepatology dept-Tanta
  • Study Director: Sherief Abd-Elsalam, lecturer, hepatology dept-Tanta
  • Study Chair: Samah Soliman, lecturer, hepatology dept-Tanta
  • Study Chair: Rehab elsheshtawi, lecturer, hepatology dept-Tanta
  • Study Chair: Mennat-Allah Elsawaf, lecturer, hepatology dept-Tanta

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Anticipated)

December 1, 2017

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

June 3, 2015

First Submitted That Met QC Criteria

June 3, 2015

First Posted (Estimate)

June 8, 2015

Study Record Updates

Last Update Posted (Actual)

August 21, 2017

Last Update Submitted That Met QC Criteria

August 16, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Hepatic encephalopathy

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Encephalopathy, Hepatic

Clinical Trials on Nitazoxanide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe