NAFLDPhase 3NCT02842567
Hydroxytyrosol and Vitamin E in Pediatric NASH
A Phase 3 study testing Hydroxytyrosol plus Vitamin E in people with NAFLD, run by Bambino Gesù Hospital and Research Institute at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 4 to 16 years
- Conditions the study is for
- NAFLD
- What is being tested?
- Hydroxytyrosol plus Vitamin E
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- 1 Apr 2017to 31 May 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site
Hepatometabolic Department, Bambino Gesù Children's Hospital
Rome, 00165
About this study
Official title: Hydroxytyrosol and Vitamin E in the Treatment of Children With Biopsy-proven NASH
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.
Read more
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.
Read the 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
- Being tested
- Hydroxytyrosol plus Vitamin E, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxytyrosol plus Vitamin EDrug
Also called Hydroxytyrosol, alpha-tocopherol
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
PlaceboDrug
This group will treated with 2 identical placebo pills daily given orally for 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Hydroxytyrosol plus Vitamin E |
| PLACEBO GROUP | Placebo comparator | This group will treated with 2 identical placebo pills daily given orally for 16 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of laboratory markers of inflammation and oxidative stress, such as concentrations of TNF-alpha, lipopolysaccharide (LPS), adiponectin, catepsin D, cytokeratin-18.
Measured: 4 months
Improvement of laboratory parameters of metabolic syndrome, such as lipids and gluco-insulinemic profile, transaminases serum levels
Measured: 4 months
Secondary outcomes (3)
Improvement of echographic score of hepatic steatosis (echographic scale)
Measured: 4 months
Number of participants with treatment-related adverse events as assessed by CTCAE
Measured: 4 months
Analysis of fecal gut microbiome of patients before and after treatment with hydroxytyrosol and vitamin E
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2016 (estimated)
- Study start1 Apr 2017
- Primary completion31 May 2018
- Study completion31 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NAFLDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bambino Gesù Hospital and Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Valerio Nobili, Bambino Gesù Hospital and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02842567
- Sponsor's protocol ID
- 1066_OPBG_2016
- Status last verified
- Jul 2017
- First submitted
- 13 Jul 2016
- Last updated
- 17 Jul 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33060043
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxytyrosol and Vitamin E in the Treatment of Children With Biopsy-proven NASH
- ClinicalTrials.gov ID
- NCT02842567
- Acronym / sponsor ID
- 1066_OPBG_2016
- Conditions
- NAFLD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Bambino Gesù Hospital and Research InstituteUniversity, hospital or other
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 31 May 2018 (actual)
- Study completion
- 31 May 2018 (actual)
- First posted
- 25 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TREATED GROUP | Experimental | Drug: Hydroxytyrosol plus Vitamin EThis 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 | Placebo comparator | Drug: PlaceboThis group will treated with 2 identical placebo pills daily given orally for 16 weeks. |
Who may qualify
- Ages
- 4 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxytyrosol plus Vitamin EAlso: Hydroxytyrosol, alpha-tocopherolThis 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 | TREATED GROUP |
| PlaceboThis group will treated with 2 identical placebo pills daily given orally for 16 weeks. | Drug | PLACEBO GROUP |
Primary outcome
Improvement of laboratory markers of inflammation and oxidative stress, such as concentrations of TNF-alpha, lipopolysaccharide (LPS), adiponectin, catepsin D, cytokeratin-18.
Time frame: 4 months
Improvement of laboratory parameters of metabolic syndrome, such as lipids and gluco-insulinemic profile, transaminases serum levels
Time frame: 4 months
3 secondary outcomes
Improvement of echographic score of hepatic steatosis (echographic scale)
Time frame: 4 months
Number of participants with treatment-related adverse events as assessed by CTCAE
Time frame: 4 months
Analysis of fecal gut microbiome of patients before and after treatment with hydroxytyrosol and vitamin E
Time frame: 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2018.
- Derived from this study: PubMed 33060043Mosca 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxytyrosol plus Vitamin E in people with NAFLD, run by Bambino Gesù Hospital and Research Institute at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of laboratory markers of inflammation and oxidative stress, such as concentrations of TNF-alpha, lipopolysaccharide (LPS), adiponectin, catepsin D, cytokeratin-18. (time frame: 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02842567, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2018.