Clinical trial NCT02464124: Nitazoxanide Plus Lactulose Versus Lactulose Alone Treatment of Hepatic Encephalopathy
Official title: A Randomized, Double-blind, Controlled Trial Comparing Nitazoxanide Plus Lactulose With Lactulose Alone Treatment of Overt Hepatic Encephalopathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Encephalopathy, Hepatic
Lead sponsor: Tanta University
Sponsor class: OTHER
Collaborators: name: Tanta University
First posted: 2015-06-08
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with total reversal of hepatic encephalopathy
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta university - faculty of medicine
state: Elgharbia
Study officials:
affiliation: hepatology dept-Tanta
name: Asem Elfert, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: hepatology dept-Tanta
name: Sherief Abd-Elsalam, lecturer
role: STUDY_DIRECTOR
affiliation: hepatology dept-Tanta
name: Samah Soliman, lecturer
role: STUDY_CHAIR
affiliation: hepatology dept-Tanta
name: Walaa elkhalawany, lecturer
role: STUDY_CHAIR
affiliation: hepatology dept-Tanta
name: Rehab elsheshtawi, lecturer
role: STUDY_CHAIR
affiliation: hepatology dept-Tanta
name: Mennat-Allah Elsawaf, lecturer
role: STUDY_CHAIR
References: