Hydroxytyrosol and Vitamin E in Pediatric NASH

Bambino Gesù Hospital and Research Institute

Status and phase

Completed

Phase 3

Conditions

NAFLD

Treatments

Drug: Placebo

Drug: Hydroxytyrosol plus Vitamin E

Study type

Interventional

Funder types

Other

Identifiers

NCT02842567

1066_OPBG_2016

Details and patient eligibility

About

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.

Full 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.

Enrollment

80 patients

Sex

All

Ages

4 to 16 years old

Volunteers

No Healthy Volunteers

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