Non Alcoholic Fatty Liver Disease
Conditions
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTMastiha
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).
DIETARY_SUPPLEMENTPlacebo
Placebo is designed to have identical characteristics with verum.
Sponsors
University of Novi Sad
National Research Council, Institute of Clinical Physiology, Italy
Harokopio University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 67 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LIF score | 6 months | Improvement in liver histopathology reflected in reduction of the sensitive LIF score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anthropometric characteristics | 6 months | BMI pre- and post- intervention in each intervention arm. |
| Genetic profile | 6 months | Profiles with a comprehensive set of genetic variants to look for markers implicated in response to Mastiha treatment. |
| Metabolomic profile | 6 months | Quantification of endogenous metabolites from different compound classes |
| NAFLD/NASH-related laboratory markers | 6 months | 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. |
| Epigenetic profile | 6 months | 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. |
| Effect of Mastiha on different BMI categories | 6 months | Identification of the effect of Mastiha on different obesity categories: Class I obesity (BMI ≤ 35) and Class II or III obesity (BMI\> 35) |
| Metagenomic profile | 6 months | Association of gut microbes with Mastiha treatment in NAFLD |
Countries
Greece
Outcome results
None listed