Hydroxytyrosol and Vitamin E in Pediatric NASH

NAFLD Clinical Trial

Official title:

Hydroxytyrosol and Vitamin E in the Treatment of Children With Biopsy-proven NASH

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02842567
• Other study ID #: 1066_OPBG_2016
• Status: Completed
• Phase: Phase 3
• Start date: April 1, 2017
• Est. completion date: May 31, 2018

Study information

• Verified date: July 2017
• Source: Bambino Gesù Hospital and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions and is rapidly becoming the one of most common causes of chronic liver disease in children. The pathogenesis of NAFLD is generally considered the result of a series of liver injuries, commonly referred as "multi-hit" hypothesis. Several studies suggest that inflammatory pathways and oxidative stress could be responsible of disease progression to non-alcoholic steatohepatitis (NASH).

Hydroxytyrosol is a simple phenolic compound naturally occurring in olive and olive oil with antioxidant properties. Some studies have demonstrated that hydroxytyrosol show several anti-inflammatory and anti-atherogenic activities, such as the inhibition of LDL oxidation and platelet aggregation.

Alpha tocopherol (Vitamin E) is the most studied anti-oxydant in pediatric NAFLD with conflicting results. It inhibits proinflammatory cytokine production and attenuates the release of profibrogenic agents and liver collagen.

The purpose of this interventional study is to evaluate the efficacy and tolerability of Hydroxytyrosol and Vitamin E in the treatment of children with biopsy-proven NASH.

Description:

80 children and adolescents (4-16 years) with biopsy-proven NASH will be enrolled. They will be randomized to treatment with hydroxytyrosol and vitamin E (n: 40 pts) or an identical placebo (n: 40 pts) given orally for a period of 16 weeks. Patients will undergo a medical evaluation at baseline (enrollment) and after 4 months (end of treatment). Anthropometric measures and laboratory assay, includin liver enzymes, gluco-insulinemic and lipid profiles will be performed at baseline and at the end of the study. Hepatic ultrasound examination will be performed at enrollment and at the end of the study.

Serum sample for determination of markers of inflammation and oxidative stress will be collected at enrollment and at the end of the study.

A stool sample for analysis of gut microbioma will be collected at enrollment and at the end of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: May 31, 2018
• Est. primary completion date: May 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 16 Years

Eligibility

Inclusion Criteria:

• Liver biopsy consistent with diagnosis of NASH (liver biopsy performed in 3-6 months before enrollment)

• Hyperechogenicity of liver at ultrasound examination

• ALT levels range between normal and < 10 UNL

• INR < 1.3

• Albumin > 3 gr/dl.

• Total bilirubin < 2.5 mg/dl

• normal renal function

• normal cells blood count

• exclusion of other causes of chronic hepatopathies in children

• Written informed consent to participate in the Protocol by their parents or legal guardians of patients

Exclusion Criteria:

• alcohols or drugs abuse

• use of drugs known to induce steatosis or to affect body weight or carbohydrate metabolism

• autoimmune liver diseases, Wilson's disease, alpha-1-antitripsin deficiency, metabolic liver disease

• every clinical or psychiatric diseases interfering with experimentation according to investigator's evaluation

• finding of active liver disease due to other causes

Related Conditions & MeSH terms

• NAFLD

Intervention

Drug:
• Hydroxytyrosol plus Vitamin E
This group will treated with 2 pills daily, each containing 3.75 mg of hydroxytyrosol plus 5 mg of Vitamin E, given orally for 16 weeks
• Placebo
This group will treated with 2 identical placebo pills daily given orally for 16 weeks.

Locations

Country	Name	City	State
Italy	Hepatometabolic Department, Bambino Gesù Children's Hospital	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Bambino Gesù Hospital and Research Institute

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of laboratory markers of inflammation and oxidative stress, such as concentrations of TNF-alpha, lipopolysaccharide (LPS), adiponectin, catepsin D, cytokeratin-18.		4 months
Primary	Improvement of laboratory parameters of metabolic syndrome, such as lipids and gluco-insulinemic profile, transaminases serum levels		4 months
Secondary	Improvement of echographic score of hepatic steatosis (echographic scale)		4 months
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE		4 months
Secondary	Analysis of fecal gut microbiome of patients before and after treatment with hydroxytyrosol and vitamin E		4 months