Hydroxytyrosol and Vitamin E in Pediatric NASH

NCT ID: NCT02842567

Last Updated: 2018-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-01
• Study Completion Date: 2018-05-31

Brief 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.

Detailed 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.

Conditions

NAFLD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TREATED GROUP

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.

Group Type: EXPERIMENTAL

Hydroxytyrosol plus Vitamin E

Intervention Type: DRUG

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 GROUP

This group will treated with 2 identical placebo pills daily given orally for 16 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

This group will treated with 2 identical placebo pills daily given orally for 16 weeks.

Interventions

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

Intervention Type: DRUG

Placebo

This group will treated with 2 identical placebo pills daily given orally for 16 weeks.

Intervention Type: DRUG

Other Intervention Names

Hydroxytyrosol, alpha-tocopherol

Eligibility Criteria

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

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Valerio Nobili

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hepatometabolic Department, Bambino Gesù Children's Hospital

Rome, , Italy

Countries

Italy

References

Mosca A, Crudele A, Smeriglio A, Braghini MR, Panera N, Comparcola D, Alterio A, Sartorelli MR, Tozzi G, Raponi M, Trombetta D, Alisi A. Antioxidant activity of Hydroxytyrosol and Vitamin E reduces systemic inflammation in children with paediatric NAFLD. Dig Liver Dis. 2021 Sep;53(9):1154-1158. doi: 10.1016/j.dld.2020.09.021. Epub 2020 Oct 13.

Reference Type: DERIVED

PMID: 33060043 (View on PubMed)

Other Identifiers

1066_OPBG_2016

Identifier Type: -

Identifier Source: org_study_id