Please select the eligibility criteria that correspond to the clinical trial below.
Title: Mastiha Treatment for Obese With NAFLD Diagnosis
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.


Options:
A: Inclusion Criteria:

1. Patients diagnosed with NAFLD by the presence of hepatic steatosis on imaging or histology in the absence of any secondary causes.
2. Patients with an ALT ≥ 1.5 upper limit of normal (ULN) and \< 5 ULN on two occasions 7 or more days apart during screening.
3. Patients with historical liver biopsy showing NASH and/or ≥ F1 fibrosis OR NFS ≥ -1.455 OR Fib- 4 ≥ 1.3 OR Fibroscan ≥8kPa within 3 months of screening.
4. Patients with a body mass index (BMI) between 25.0 and 40.0 kg/m² inclusive. Patients with a history of controlled obesity or controlled diabetes are allowed on the study.
5. Patients whose pre-study clinical laboratory findings do not interfere with their participation in the study, in the opinion of the Investigator.
6. Patients aged between 18 and 75 years inclusive.
7. Female patients and male patients with female partners of child bearing potential must use adequate contraception or have a sterilized partner for the duration of the study. Adequate contraception is defined as: systemic hormonal contraceptives; intrauterine device or barrier method of contraception in conjunction with spermicide; or agree to sexual abstinence, defined as a patient refraining from heterosexual intercourse during the entire period of risk associated with the study treatments and in line with their preferred and usual lifestyle. Hormonal contraceptives must be on a stable dose for at least one month before baseline.
8. Patients who are able to communicate well with the Investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent.

Exclusion Criteria:

1. Patients with an unstable metabolic condition such as weight change \> 5% in the 3 months prior to inclusion.
2. Patients with medical/surgical history of gastric bypass surgery, orthotopic liver transplant (OLT) or listed for OLT.
3. Patients with uncontrolled diabetes mellitus type 2, i.e. HbA1c ≥ 9% (75 mmol/mol) at the time of screening.
4. Patients with decompensated or severe liver disease as evidenced by one or more of the following: confirmed cirrhosis or suspicion of cirrhosis, esophageal varices, ascites, suspicion of portal hypertension, hospitalization for liver disease within 60 days of screening, bilirubin ≥ 2 x ULN, or ALT or AST ≥ 5 x ULN. Patients with Gilbert's syndrome are eligible if the conjugated bilirubin is ≤ 1.5 x ULN.
5. Patients with inflammatory bowel disease that is either active or requiring medical therapy.
6. Patients with diagnosed or suspected autoimmune diseases such as systemic lupus erythematosus and/or rheumatoid arthritis.
7. Patients with a history of or active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas).
8. Patients with a significant systemic or major illness other than liver disease, including coronary artery disease, cerebrovascular disease, pulmonary disease, renal insufficiency, serious psychiatric disease, respiratory or hypertensive disease, as well as diabetes and arthritis that, in the opinion of the Investigator, would preclude the patient from participating in and completing the study.
9. Patients requiring anti-diabetic treatment (including insulin sensitizing agents), and/or lipid lowering treatment, and who are not on a stable dose for at least 3 months prior to screening should be excluded. If patients are insulin dependent this treatment should have commenced at least 3 months prior to screening, however changes in dose are permitted.
10. Patients with known hypersensitivity to any ingredients of the study treatment.
11. Patients with a positive test for human immunodeficiency virus antibodies, Hepatitis B surface antigen or Hepatitis C antibodies at screening.
12. Patients with liver disease of other etiologies such as drug-induced, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, haemochromatosis, alpha-1 antitrypsin deficiency or Wilson's disease.
13. Patients with a significant history of drug/solvent abuse, in the opinion of the investigator.
14. Patients with a history of alcohol abuse in the opinion of the Investigator, or who currently drinks in excess of 21 units per week (males) or 14 units per week (females), whereby a unit consists of 10ml or 8mg of pure alcohol.
15. Patients who have used dietary supplements rich in omega-3 or omega-6 fatty acids in the 4 weeks prior to baseline.
16. Patients who have participated in any other clinical study with an investigational drug within 3 months before the first day of administration of study treatment.
17. Patients who are pregnant, planning pregnancy, breastfeeding and/or are unwilling to use adequate contraception (as specified in inclusion criterion 7) during the study.
18. Patients, in the opinion of the Investigator, not suitable to participate in the study.
B: 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
C: Inclusion Criteria:

* Liver biopsy confirmed NASH (NAS score greater than or equal to 5)
* BMI \>25 kg/m2 (Caucasians)
* \>23 kg/m2 (Asians)
* History of Serum ALT \>1.5X upper normal limit
* No changes in lipid-lowering or diabetes medication over previous three months
* Ability to provide informed consent

Exclusion Criteria:

* alcohol consumption \>20g/day (women) or \>30g/day (men)
* alternate etiology for abnormal liver enzymes
* decompensated liver disease
* use of orlistat, liraglutide, prebiotic, probiotic, or antibiotic within 3 months prior to enrollment
D: 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

Answer: D