protocolSection identificationModule nctId: NCT06314932, orgStudyIdInfo id: spe123.23, briefTitle: Role of Ultra-processed Foods in Modulating the Effect of Mediterranean Diet, acronym: PROMENADE, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04, primaryCompletionDateStruct date: 2024-10, completionDateStruct date: 2025-06, studyFirstPostDateStruct date: 2024-03-18, lastUpdatePostDateStruct date: 2024-03-18, sponsorCollaboratorsModule leadSponsor name: University of Milan, class: OTHER, collaborators name: University of Florence, collaborators name: University of Teramo, descriptionModule briefSummary: Mediterranean diet is worldwide promoted as one of the healthiest and most sustainable dietary patterns. One of the main pillars of Mediterranean diet is the abundant consumption of plant-based ingredients typically consumed as raw or minimally processed. However, even in the Mediterranean countries, these fresh foods are increasingly replaced by ultra-processed foods (UPF). Epidemiological evidence suggests that consumption of UPF may be detrimental to human health, but there is only one clinical trial on this topic which is largely debated in the scientific community due to limitations related to the short duration of the trial and the composition of dietary interventions.The present study aims at exploring whether the inclusion of UPF within a Mediterranean-based dietary pattern can impact on cardiometabolic markers, gut microbiota and other health markers in a dietary intervention performed in Italian subjects. For this purpose, 50 clinically healthy subjects will be recruited for a 7-month randomized, open, cross-over dietary trial. Eligible participants will be randomly assigned to consume a 3-month Mediterranean diet high in UPF (intervention group) or a low-UPF Mediterranean diet (control group), spaced by a 1-month wash-out period. The two diets will have the same composition in terms of food groups. However, in the high-UPF Mediterranean diet group, 5 servings/day of UPF, as defined by the NOVA system, will be consumed (e.g., flavored yogurt, breakfast cereals with added sugar, processed meat). In the control group, these foods will be replaced by products from the same food group, but not UPF (e.g., plain yogurt, breakfast cereals with no added sugar, unprocessed meat). The inflammatory potential of pairs of food products, both UPF and non UPF, will be evaluated using an in vitro cell model testing the modulation of inflammatory markers. Before and after each intervention blood, urine and fecal samples will be collected. The primary endpoint is change in low-density lipoprotein (LDL) cholesterol levels from baseline. Among the other markers, blood pressure and anthropometric parameters will be measured; biochemical parameters, adipokines, inflammatory and oxidative stress markers, fecal microbiota composition and short chain fatty acids (SCFAs) will be analyzed. Adherence to the study, dietary intake and food waste production will be evaluated through specific food diaries, useful also for estimating the metabolic food waste., conditionsModule conditions: Overweight, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: CROSSOVER, primaryPurpose: PREVENTION, maskingInfo masking: SINGLE, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 50, type: ESTIMATED, armsInterventionsModule interventions name: MD high in UPF, interventions name: MD low in UPF, outcomesModule primaryOutcomes measure: Low-density lipoprotein (LDL) cholesterol levels, secondaryOutcomes measure: Total cholesterol levels, secondaryOutcomes measure: High-density lipoprotein (HDL) cholesterol levels, secondaryOutcomes measure: Triglycerides levels, secondaryOutcomes measure: Fasting blood glucose levels, secondaryOutcomes measure: Insulin levels, secondaryOutcomes measure: Aspartate aminotransferase (AST) levels, secondaryOutcomes measure: Alanine aminotransferase (ALT) levels, secondaryOutcomes measure: Gamma-glutamyl transferase (GGT) levels, secondaryOutcomes measure: Folates levels, secondaryOutcomes measure: Vitamin B12 levels, secondaryOutcomes measure: Urea levels, secondaryOutcomes measure: Creatinine levels, secondaryOutcomes measure: Body weight, secondaryOutcomes measure: Body mass index (BMI), secondaryOutcomes measure: Fat mass, secondaryOutcomes measure: Concentration of ghrelin in plasma, secondaryOutcomes measure: Concentration of leptin in plasma, secondaryOutcomes measure: Concentration of adiponectin in plasma, secondaryOutcomes measure: Concentration of resistin in plasma, secondaryOutcomes measure: Concentration of visfatin in plasma, secondaryOutcomes measure: Concentration of interleukin (IL)-4 in plasma, secondaryOutcomes measure: Concentration of interleukin (IL)-6 in plasma, secondaryOutcomes measure: Concentration of interleukin (IL)-10 in plasma, secondaryOutcomes measure: Concentration of Protein C-reactive (PCR) in plasma, secondaryOutcomes measure: Concentration of interferon gamma (IFN-γ) in plasma, secondaryOutcomes measure: Concentration of tumor necrosis factor -alpha (TNF-α) in plasma, secondaryOutcomes measure: DNA damage expressed as number of DNA strand breaks induced by hydrogen peroxide (H2O2), secondaryOutcomes measure: Concentration of F2-isoprostanes in urine, secondaryOutcomes measure: Gut microbiota composition and function changes, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: University of Florence, city: Florence, zip: 54141, country: Italy, contacts name: Monica Dinu, role: CONTACT, phone: +39 349 3465184, email: monica.dinu@unifi.it, geoPoint lat: 43.77925, lon: 11.24626, locations facility: University of Milan, city: Milan, zip: 20133, country: Italy, contacts name: Daniela Martini, role: CONTACT, phone: +39 02503 16727, email: daniela.martini@unimi.it, geoPoint lat: 45.46427, lon: 9.18951, hasResults: False