Hydroxytyrosol and Vitamin E in Pediatric NASH

NCT02842567 | Completed Phase 3

• 1 other identifier: 1066_OPBG_2016
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

NAFLD

Outcome Measures

Primary Outcomes (2)

• Improvement of laboratory markers of inflammation and oxidative stress, such as concentrations of TNF-alpha, lipopolysaccharide (LPS), adiponectin, catepsin D, cytokeratin-18.

  4 months

• Improvement of laboratory parameters of metabolic syndrome, such as lipids and gluco-insulinemic profile, transaminases serum levels

  4 months

Secondary Outcomes (3)

• Improvement of echographic score of hepatic steatosis (echographic scale)

  4 months

• Number of participants with treatment-related adverse events as assessed by CTCAE

  4 months

• Analysis of fecal gut microbiome of patients before and after treatment with hydroxytyrosol and vitamin E

  4 months

Study Arms (2)

TREATED GROUP

EXPERIMENTAL

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.

Drug: Hydroxytyrosol plus Vitamin E

PLACEBO GROUP

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Hydroxytyrosol plus Vitamin E 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

Also known as: Hydroxytyrosol, alpha-tocopherol

TREATED GROUP

Placebo DRUG

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

PLACEBO GROUP

Eligibility Criteria

• Age: 4 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute: lead

Study Sites (1)

Hepatometabolic Department, Bambino Gesù Children's Hospital

Rome, 00165, Italy

Location

Related Publications (1)

• 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.

  PMID: 33060043 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

3,4-dihydroxyphenylethanol; Vitamin E; alpha-Tocopherol

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tocopherols

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 25, 2016
• Study Start: April 1, 2017
• Primary Completion: May 31, 2018
• Study Completion: May 31, 2018
• Last Updated: July 17, 2018

Record last verified: 2017-07

Locations

IT (1)