Nitazoxanide Plus Lactulose Versus Lactulose Alone Treatment of Hepatic Encephalopathy

Encephalopathy, Hepatic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02464124
• Other study ID #: Hepatic encephalopathy
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: June 3, 2015
• Last updated: August 16, 2017
• Start date: January 2016
• Est. completion date: December 2017

Study information

• Verified date: August 2017
• Source: Tanta University
• Contact: Sherief Abd-elsalam, lecturer
• Phone: 00201095159522
• Email: Sheriefabdelsalam[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Encephalopathy, Hepatic
• Hepatic Encephalopathy

Intervention

Drug:
• Nitazoxanide
• Nitazoxanide dosing: 500 mg tablets twice daily
• Lactulose
• Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day

Locations

Country	Name	City	State
Egypt	Tanta university - faculty of medicine	Tanta	Elgharbia

Sponsors (2)

Lead Sponsor	Collaborator
Sherief Abd-Elsalam	Tanta University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with total reversal of hepatic encephalopathy		6 months