Spontaneous, non-sponsored, interventional, controlled, randomized, parallel-arm clinical study.
Primary objective To assess the impact of specific dietary approaches (ketogenic diet, Mediterranean diet, or Mediterranean diet supplemented with GABA-producing probiotics, e.g., Bifidobacterium adolescentis PRL2019) on fibromyalgia (FM) severity-particularly pain, sleep quality, anxiety, and depression-using validated questionnaires in female patients with FM and overweight/class I obesity.
Secondary objectives
* Evaluate effects on anthropometric measures, metabolic profile, and body composition. * Assess changes in gut microbiota composition and metabolomic analysis. * Measure neurosteroids with positive allosteric activity on GABA-A or NMDA receptors in saliva and/or plasma. * Exploratory pilot sub-study to quantify brain GABA and glutamate levels through magnetic resonance spectroscopy (MRS) in a subset of patients.
Methods Participants will be recruited from the Rheumatology Unit outpatient clinics of IRCCS Policlinico San Martino Hospital (Genoa). Eligible subjects will be adult women with FM and overweight/obesity, selected through protocol-defined criteria. Enrollment requires written informed consent.
At enrollment (baseline), participants will complete validated questionnaires assessing FM severity (pain, sleep quality, depression, anxiety, bowel function). Data collection will include sociodemographic information, Mediterranean diet adherence through PREDIMED questionnaire, basal metabolic rate, medical and dietary history, smoking status, blood pressure, and recent laboratory results. Stool, blood, and saliva samples will be collected for routine tests, metabolomics, and ELISA-based measurement of neuroactive steroids like cortisol, progesterone, DHEA.
Within 7 days T1, results will be reviewed and eligible participants randomized to one of three groups: hypocaloric ketogenic diet, Mediterranean diet, or Mediterranean diet plus probiotics. Individualized dietary plans will be provided with written and verbal instructions.
Anthropometric measurements (weight, height, BMI, waist circumference, waist-hip ratio) and body composition via bioelectrical impedance analysis BIA will be recorded at T0, T4, T8, and T12, together with biological sample collection.
Pilot MRS sub-study A subset of participants will undergo brain GABA and glutamate assessment through MRI spectroscopy performed on a 3T Siemens - Prisma magnet at the baseline, before dietary treatment and after 4 weeks. Results will be compared with spectra from control subjects screened through medical history to exclude relevant diseases.
Adult female patients with fibromyalgia, aged ≤ 65 years, who are overweight or obese (BMI 24.9 < ≤34.9 kg/m2);
Patients able to independently provide their written informed consent to participate in the study;
Patients motivated to participate in the project and able to independently manage the dietary plans provided for in the study.
Lack of signature on informed consent form
Age < 18 and > 65 years
Male gender
Patients with food allergies or celiac disease, type 1 diabetes mellitus and autoimmune forms of diabetes mellitus or with severe pancreatic beta cell dysfunction, undergoing treatment with SGLT2 inhibitors, with recent cardiovascular or cerebrovascular events, liver failure, moderate or severe renal failure, respiratory failure, episodes of gout, kidney stones, electrolyte disturbances, NYHA class III-IV heart failure, unstable angina, cardiac arrhythmias or myocardial infarction within the last 12 months, severe depression or any other psychiatric illness, drug, narcotic or alcohol abuse, frail patients, pregnancy and/or breastfeeding, patients about to undergo surgery or invasive procedures, rare diseases (porphyria, carnitine deficiency, carnitine palmitoyltransferase, carnitine acylcarnitine translocase and pyruvate carboxylase, mitochondrial beta oxidation disorders), treatment with diuretics.
Universita degli Studi di Genova
Lead sponsor
Ospedale Policlinico San Martino
Collaborator
Istituto Giannina Gaslini
Collaborator