Dietary Strategies for the Treatment of Fibromyalgia in Overweight and Obese Patients

Summary

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.

Conditions

• Fibromyalgia (FM)

Interventions

BEHAVIORAL

Very Low-Calorie Ketogenic Diet

The very low calorie ketogenic diet (VLCKD) is a diet characterized by a very low carbohydrate content and reduced calorie intake, while maintaining an adequate amount of protein. In this study, subjects will receive food kits and supplements prepared by SDM, a company belonging to the Pronokal group. The VLCKD involves three different phases of intervention: the 4-week attack phase (phase l), the transition phase (phase Il), and the maintenance phase (phase III). Phase I is characterized by an 800 kcal diet with 1.2 g/kg/ideal weight of protein, 10-15 g of lipids, and 45-70 g of carbohydrates. Phase Il (four weeks) aims to gradually reintroduce carbohydrates, increase calorie intake and reduce consumption of Pronokal products. Phase Ill involves maintenance through a low-calorie Mediterranean-style diet in line with the other arms interventions, of 1400 kcal/day for another 4 weeks.

BEHAVIORAL

Mediterranean diet

A standardized low-calorie diet of 1400 kcal/day will be drawn up. The macronutrient breakdown will follow the Reference Intake Levels for Nutrients and Enerav (LARN V edition), providing for: 0.9 g/day/kg of ideal body weight of protein, 48% carbohydrates, and 30-35% lipids. The daily calorie breakdown will be: 15% of calories for breakfast, 35-40% for lunch, 30-35% for dinner, and 10% of the remaining calories to be divided into two snacks. Each patient must follow the Mediterranean Diet for the entire duration of the treatment, i.e., 12 weeks, during which any necessary changes will be made to ensure full compliance with the diet plan.

BEHAVIORAL

Mediterranean diet enriched by GABA-producing probiotic

Standardized low-calorie diet of 1400 kcal/day characterized by: 0.9 g/day/kg of ideal body weight of protein, 48% carbohydrates, and 30-35% lipids. The daily calorie breakdown will be: 15% of calories for breakfast, 35-40% for lunch, 30-35% for dinner, and 10% of the remaining calories to be divided into two snacks. This diet will also be enriched with GABA-producing probiotics such as Bifidobacterium adolescentis PRL2019 (20 CFU/day) present in Gabapral produced by Pharmextracta S.p.A.

Sponsors & Collaborators

• Ospedale Policlinico San Martino

  collaborator OTHER

• Istituto Giannina Gaslini

  collaborator OTHER

• Universita degli Studi di Genova

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-30

Primary Completion

2027-12-31

Completion

2028-06-30

Countries

• Italy

Study Locations