Clinical trial NCT04442620: Prevention and Reversion of NAFLD in Obese Patients With Metabolic Syndrome by Mediterranean Diet and Physical Activity
Official title: Prevention and Reversion of Non-Alcoholic Fatty Liver Disease in Obese Patients With Metabolic Syndrome by Mediterranean Diet and Physical Activity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non Alcoholic Fatty Liver Disease
Keywords: Non Alcoholic Fatty Liver Disease
Metabolic syndrome
Mediterranean Diet
Physical activity
Lead sponsor: University of the Balearic Islands
Sponsor class: OTHER
Collaborators: name: Fundació La Marató de TV3
First posted: 2020-06-22
Enrollment: 150
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This prospective randomized trial evaluates the role of customized dietary and physical activity intervention on the progression of Non-Alcoholic Fatty Liver Disease (NAFLD) in patients with obesity and presenting at least three of the main Metabolic Syndrome traits.

The project proposes a personalized nutritional intervention based on a Mediterranean customized diet which introduces plenty of antioxidant and anti-inflammatory bioactive components, coupled with physical activity promotion to prevent and reverse NAFLD among obese patients with metabolic syndrome. This will be compared with two more dietary strategies including a Mediterranean Diet intervention with seven meals a day and the conventional dietary approach proposed by the American Association for the Study of Liver Diseases (AASLD).

Detailed description: There is currently no licensed pharmacological treatment for reversing Non-Alcoholic Fatty Liver Disease (NAFLD), this is why nutritional and lifestyle strategies are pivotal to ameliorate risk factors and prevent disease progression. Weight loss achieved by a weight loss diet and exercise is certainly the principal treatment for the amelioration of fatty liver, nevertheless quality of diet composition could also play a crucial role. Since oxidative stress and inflammation have been cited among the mechanisms involved in NAFLD, foods containing antioxidant and anti-inflammatory bioactive components should be considered when designing a nutritionally sound diet. The Mediterranean Diet, naturally rich in antioxidants and antinflammatory foods, together with personalised physical activity could have a variety of positive health effects, including the slowing down of degenerative diseases such as liver steatosis.

The present study aims to compare and evaluate the efficacy of three interventions on the pathophysiological mechanisms that may affect changes in liver fat deposits and progression of NAFLD in patients with obesity and presenting at least three of the main Metabolic Syndrome traits.

The first intervention group receives a caloric restricted Mediterranean Diet coupled with physical activity (delivered through guided gym classes); the second group receives a caloric restricted Mediterranean Diet distributed over 7 meals and advise to walk 10.000 steps a day; the third group receives the conventional diet proposed by the American Association for the Study of Liver Diseases (AASLD) and advise to walk 10.000 steps a day.

Eligibility criteria: Inclusion Criteria:

* Age between 40 and 60 years
* Diagnosis of NAFLD by ultrasound
* BMI ≥ 27 and \< 40 kg/m2
* Meeting at least 3 of 5 criteria for the metabolic syndrome \[as described in the International Diabetes Federation consensus\]: (1) BMI \>30kg/m² or increased waist circumference: ≥ 94 cm in males; ≥ 80 cm in females; (2) Triglycerides (TG) levels ≥ 150 mg/dL (1.7 mmol/L) or specific treatment; (3) Reduced HDL cholesterol: \< 40 mg/dL (1.03 mmol/L) in males; \< 50 mg/dL (1.29 mmol/L) in females or specific treatment; (4) Raised blood pressure: systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg or treatment of previously diagnosed hypertension; (5) Raised fasting plasma glucose (FPG) ≥ 100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes
* Written informed consent

Exclusion Criteria:

* Inability or unwillingness to give informed consent or communicate with staff study
* Documented history of prior cardiovascular disease \[angina; myocardial infarction; coronary revascularization procedures; stroke (ischemic or hemorrhagic including transient ischemic attacks); symptomatic peripheral artery disease that required surgery or was diagnosed with vascular imaging techniques; ventricular arrhythmia; uncontrolled atrial fibrillation; congestive heart failure (New York Heart Association Class III or IV); hypertrophic myocardiopathy; and history of aortic aneurism \>=5.5cm in diameter or aortic aneurism surgery\]
* Documented history of prior liver diseases (other than NAFLD)
* Active cancer or a history of malignancy in the last 5 years
* Low predicted probability to change food habits according to the Stages of Change Model (Nigg, 1999)
* Unwillingness or inability to adhere to the dietary and physical activity intervention over the entire period of the study
* Failure to follow scheduled visits
* Weight loss (\>5 kg) during 6 months prior to visit
* Previous surgical procedures for weight loss or scheduled bariatric surgery within the next 12 months
* Use of weight loss medications during 6 months prior to visit
* Previous history of bowel resection, inflammatory bowel disease
* Obesity associated with endocrine disease (except treated hypothyroidism)
* Allergy to Mediterranean diet foods or components
* Severe psychiatric disorders (schizophrenia, bipolar disorder, eating disorders, or depression with hospitalization within the last 6 months) or Beck Depression Inventory score \> 30
* Severe condition with less than 24 months life expectancy
* Chronic abuse of drugs or alcohol (\>21 and \>14 units of alcohol a week for men and women, respectively; 1 unit = 125 mL of wine)
* Treatment with steroids
* Pregnancy

Primary outcomes:
measure: Changes in liver steatosis
timeFrame: At baseline, 6, 12 and 24 months
Secondary outcomes:
measure: Changes in liver fibrosis
timeFrame: At baseline, 6, 12 and 24 months
Other outcomes:
Locations:
city: Palma
country: Spain
facility: University of the Balearic Islands
state: Balearic Islands
Study officials:
affiliation: University of the Balearic Islands
name: Josep A Tur, PhD
role: PRINCIPAL_INVESTIGATOR
References: