Mastiha Treatment for Obese With NAFLD Diagnosis

Study Overview
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Brief Summary
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NAFLD/NASH is one of the most common complications of obesity and diabetes mellitus in Western populations affecting approximately 50% of diabetics and 76% of obese patients. Due to the lack of specialized treatment, many new efforts focus on exploring alternative, non-pharmacologic means for managing the disease, including bioactive substances in fruits, vegetables and plants or their products. Mastiha, a natural product of Greece, consists of a great variety of bioactive phytochemical compounds and demonstrates antioxidant, antiinflammatory, antimicrobial and lipid lowering properties. Taking into account the contribution of oxidative stress and inflammation to NAFLD/NASH pathogenesis, the hypothesis that Mastiha could improve disease aspects is investigated. Thus, design of a multicenter (4 centers across Europe), randomized, double-blind, placebo controlled (parallel arm) clinical trial to assess the effect of Mastiha on clinical course of NAFLD/NASH patients has been conducted. The effectiveness of the proposed intervention will be evaluated via clinical and laboratory markers. MAST4HEALTH aims also at exploring gene-diet interactions and at correlating genetic and epigenetic markers with metabolomic and intestinal microbiota profiles pre- and post- intervention. To this end, patients with confirmed NAFLD/NASH will be allocated to either verum or placebo group. Duration of the intervention will be 6 months and the dosage applied will be 2.1 g daily. NAFLD/NASH diagnosis will be confirmed by MS scanning and the sensitive LiverMultiScan technique. Anthropometric, demographic data, body composition, dietary habits, physical activity, family history and smoking status will be assessed pre- and post- intervention. Biochemical profile, oxidative stress and inflammation, as well as epigenetic and metabolomic profiles will be assessed in blood samples, while the metagenome profile will be examined in stools. Both groups will receive counselling to allow for body weight regulation up to 5%. Compliance will be assessed monthly and side effects will be reported.

Official Title
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Mastiha Treatment for Obese With NAFLD Diagnosis

Conditions
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Non Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Mastiha
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed NAFLD/NASH 18 years < Age < 67 years BMI > 30 kg/ m2 Exclusion Criteria: Hepatotoxic Medication, Concomitant Liver Disease Decompensated Diabetes Mellitus Dysthyroidism, hypopituitarism, Cushing syndrome / disease Alcohol abuse or drug addiction Clinically or biochemically recognized systemic diseases Pregnancy test, lactation Vegan or lacto- and ovo-lacto- vegetarianism Psychiatric or mental disorder Recent loss in body weight or current diet Any use of antioxidant-phytochemical rich supplement, anti-, pre- or pro-biotics within 3 months pre-intervention Changes in drug treatment for e.g. hypertension, diabetes mellitus, 3 months prior or during the 6month intervention Antibiotic treatment during and 2 months prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 67 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mastiha<br>This arm of patients will receive natural Mastiha supplements at a daily dosage of 2.1 g for a 6 month period. | Dietary Supplement: Mastiha<br>* Mastiha is a natural product of Greece and has a license of manufactures Foods for Particular Nutritional Uses and of National Organization of Medicines (EOF).<br>|
| Placebo Comparator: Placebo<br>This arm of patients will receive placebo for a 6 month period. | Dietary Supplement: Placebo<br>* Placebo is designed to have identical characteristics with verum.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LIF score | Improvement in liver histopathology reflected in reduction of the sensitive LIF score | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NAFLD/NASH-related laboratory markers | Liver enzymes improvement, inflammation and oxidative stress markers improvement (e.g. IL-6, IL-10, TNF-α, GSH, Gpx), lipid profile improvement, insulin sensitivity improvement pre- and post- intervention in each intervention arm. | 6 months | 
| Anthropometric characteristics | BMI pre- and post- intervention in each intervention arm. | 6 months | 
| Genetic profile | Profiles with a comprehensive set of genetic variants to look for markers implicated in response to Mastiha treatment. | 6 months | 
| Metabolomic profile | Quantification of endogenous metabolites from different compound classes | 6 months | 
| Metagenomic profile | Association of gut microbes with Mastiha treatment in NAFLD | 6 months | 
| Epigenetic profile | Identification of the subset of variably methylated regions with low within-individual variability over the six months period of the study to correlate them to treatment. | 6 months | 
| Effect of Mastiha on different BMI categories | Identification of the effect of Mastiha on different obesity categories: Class I obesity (BMI ≤ 35) and Class II or III obesity (BMI> 35) | 6 months |