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

NCT07517757 | Not Yet Recruiting

• 1 other identifier: Liguria: 400/2025 - ID 14696
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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)

Keywords

Fibromyalgia; questionnaires; dietary intervention; obesity; gut microbiota; probiotics; gut-brain-axis; GABA; glutamate; magnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (7)

• Assessing the impact of dietary approach on the severity of fibromyalgia, particularly on pain through the Widespread Pain Index (WPI)

  Widespread Pain Index (WPI): this corresponds to the sum of the areas of pain present (ranging from 0 to 19).

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Assessing the impact of dietary approach on the severity of fibromyalgia, particularly on pain through the Symptom Severity Scale (SSS).

  Symptom Severity Scale (SSS): this corresponds to the sum of the severity levels of three symptoms (fatigue, non-restorative sleep, cognitive problems), measured on a 4-point ordinal scale, and the presence or absence of three other symptoms (migraine, abdominal pain/cramps, depression). The maximum possible score is 12.

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Assessing the impact of dietary approach on the severity of fibromyalgia, particularly on pain through the Fibromyalgia Impact Questionnaire (FIQR).

  The FIQR comprises 21 questions, structured on numerical rating scales ranging from 0 to 10. The questions are divided into three distinct domains: physical function (9 questions), relating to difficulty in performing common activities of daily living; general health status (2 questions), which investigates the impact of the condition on work performance; and self-assessment of the intensity/severity of condition-related symptoms (10 questions).

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Assessing the impact of dietary approach on the severity of fibromyalgia, particularly on pain through the PainDETECT (PD-Q).

  The PainDETECT (PD-Q) consists of a series of questions designed to identify the type, location (including any radiating pain) and intensity of the pain. It also includes an image of a figure shown from the front and back, on which the patient must indicate the area affected by the pain.The score ranges from 0 to 35 and is directly proportional to the likelihood of the pain being neuropathic. More specifically, a final score of less than 12 indicates that neuropathic pain is unlikely, whilst a score of more than 19 indicates that the pain is very likely to be neuropathic.

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Assessing the impact of dietary approach on the severity of fibromyalgia, particularly on anxiety and depression through The Hospital Anxiety and Depression Scale (HADS).

  The Hospital Anxiety and Depression Scale (HADS) is a 14-item, self-report screening tool designed to detect emotional distress (anxiety and depression) in clinical settings, particularly for people with physical health conditions. It includes seven anxiety questions and seven depression questions, excluding physical symptoms to avoid overlapping with medical diagnoses: 14 items, with 7 assessing anxiety (HADS-A) and 7 assessing depression (HADS-D). Each item is rated on a 4-point scale (0 to 3), resulting in subscale scores ranging from 0 to 21.Generally, scores \< = 7 are "normal", 8-10 are borderline and \>= 11indicate a "case" of significant psychological morbidity.

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Assessing the impact of dietary approach on the severity of fibromyalgia, particularly on sleep quality through the Pittsburgh Sleep Quality Index (PSQI).

  Each component score of the PSQI ranges from 0 to 3, with 3 indicating the greatest dysfunction or disturbance. The seven component scores are then summed to obtain a global PSQI score, which ranges from 0 to 21. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficulties.

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Assess the presence of functional gastrointestinal disorders, in particular Irritable Bowel Syndrome (IBS) through the Rome IV criteria and the Bristol Stool Scale.

  The Rome IV Criteria are a standardized diagnostic questionnaire used to identify functional gastrointestinal disorders, such as irritable bowel syndrome (IBS), functional constipation, and functional diarrhea. Its a checklist-based system: * Presence/absence of symptoms * Frequency and duration * Association with bowel habits. The Bristol Stool Scale is a visual classification tool used to categorize stool form into 7 types. The 7 Types Type 1 - Separate hard lumps (severe constipation) Type 2 - Sausage-shaped but lumpy (mild constipation) Type 3 - Like a sausage with cracks on the surface (normal) Type 4 - Smooth, soft sausage or snake (normal, ideal) Type 5 - Soft blobs with clear edges (lacking fiber) Type 6 - Fluffy pieces, mushy (mild diarrhea) Type 7 - Watery, no solid pieces (severe diarrhea) Evaluation Scale It is a 7-point ordinal scale: 1-2 → Constipation 3-4 → Normal stool 5 → Borderline 6-7 → Diarrhea

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

Secondary Outcomes (6)

• Assess adherence to the Mediterranean diet and the impact of the dietary approach on anthropometric measurements.

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Evaluate the impact of dietary intervention on the composition of the gut microbiota through metabolomic analysis.

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Assessment of neurosteroids with positive allosteric action on GABA-A receptors or NMDA receptors in saliva and/or plasma.

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

• Exploratory pilot sub-study to measure brain levels of GABA and glutamate using magnetic resonance imaging (MRI) in a small sample of patients (18 patients + 6 controls).

  Baseline, Week 4.

• Assess the impact of the dietary approach on metabolic parameters.

  Baseline, Week 4, Week 8, and at the end of treatment (up to 12 weeks).

Study Arms (3)

Very Low-Calorie Ketogenic Diet (VLCKD)

EXPERIMENTAL

30 patients in the study will follow a standardised Very Low Calorie Ketogenic Diet (VLCKD). The intervention will be conducted under medical and nutritional supervision for the entire duration of the study through follow-up visits and telephone contact as necessary.

Behavioral: Very Low-Calorie Ketogenic Diet

Mediterranean Diet

EXPERIMENTAL

30 patients in the study will follow a standardized Mediterranean diet. The intervention will be conducted under medical and nutritional supervision for the entire duration of the study through follow-up visits and telephone contact as necessary.

Behavioral: Mediterranean diet

Mediterranean Diet enriched by GABA- producing probiotic

EXPERIMENTAL

30 patients in the study will follow a standardised Mediterranea Diet enriched by GABA-producing probiotic. The intervention will be conducted under medical and nutritional supervision for the entire duration of the study through follow-up visits and telephone contact as necessary.

Behavioral: Mediterranean diet enriched by GABA-producing probiotic

Interventions

Very Low-Calorie Ketogenic Diet BEHAVIORAL

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.

Very Low-Calorie Ketogenic Diet (VLCKD)

Mediterranean diet BEHAVIORAL

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.

Mediterranean Diet

Mediterranean diet enriched by GABA-producing probiotic BEHAVIORAL

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.

Mediterranean Diet enriched by GABA- producing probiotic

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Use of prebiotics and/or probiotics not included in the study, or other dietary supplements in the month prior to enrollment
• Antibiotic treatment less than 3 months prior to enrollment
• Infections at the time of enrollment or any chronic gastrointestinal disorder (e.g., Crohn's disease)
• Significant eating problems (e.g., dysphagia).

Sponsors & Collaborators

• Universita degli Studi di Genova: lead
• Ospedale Policlinico San Martino: collaborator
• Istituto Giannina Gaslini: collaborator

Study Sites (1)

Department of Internal and Medical Specialities (university of Genoa)

Genova, Genova, 16132, Italy

Location

Related Publications (7)

• Sarzi-Puttini P, Giorgi V, Marotto D, Atzeni F. Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nat Rev Rheumatol. 2020 Nov;16(11):645-660. doi: 10.1038/s41584-020-00506-w. Epub 2020 Oct 6.

  PMID: 33024295 BACKGROUND

• Demori I, Giordano G, Mucci V, Losacco S, Marinelli L, Massobrio P, Blanchini F, Burlando B. Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey. J Comput Neurosci. 2022 Nov;50(4):471-484. doi: 10.1007/s10827-022-00826-8. Epub 2022 Jul 11.

  PMID: 35816263 BACKGROUND

• Ustianowska K, Ustianowski L, Machaj F, Goracy A, Rosik J, Szostak B, Szostak J, Pawlik A. The Role of the Human Microbiome in the Pathogenesis of Pain. Int J Mol Sci. 2022 Oct 31;23(21):13267. doi: 10.3390/ijms232113267.

  PMID: 36362056 BACKGROUND

• D'Onghia M, Ciaffi J, Lisi L, Mancarella L, Ricci S, Stefanelli N, Meliconi R, Ursini F. Fibromyalgia and obesity: A comprehensive systematic review and meta-analysis. Semin Arthritis Rheum. 2021 Apr;51(2):409-424. doi: 10.1016/j.semarthrit.2021.02.007. Epub 2021 Mar 3.

  PMID: 33676126 BACKGROUND

• Proietti E, Rapallo F, Molinari E, Mucci V, Marinelli L, Borgarelli C, Burlando B, Pisciotta L, Demori I. Online Questionnaire with Fibromyalgia Patients Shows Negative Correlations between Disease Severity and Adherence to Mediterranean Diet. Nutrients. 2024 Apr 6;16(7):1078. doi: 10.3390/nu16071078.

  PMID: 38613111 BACKGROUND

• Ciaffi J, Lisi L, Mari A, Mancarella L, Brusi V, Pignatti F, Ricci S, Vitali G, Stefanelli N, Assirelli E, Neri S, Naldi S, Faldini C, Ursini F. Efficacy, safety and tolerability of very low-calorie ketogenic diet in obese women with fibromyalgia: a pilot interventional study. Front Nutr. 2023 Jul 12;10:1219321. doi: 10.3389/fnut.2023.1219321. eCollection 2023.

  PMID: 37502721 BACKGROUND

• Duranti S, Ruiz L, Lugli GA, Tames H, Milani C, Mancabelli L, Mancino W, Longhi G, Carnevali L, Sgoifo A, Margolles A, Ventura M, Ruas-Madiedo P, Turroni F. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci Rep. 2020 Aug 24;10(1):14112. doi: 10.1038/s41598-020-70986-z.

  PMID: 32839473 BACKGROUND

MeSH Terms

Conditions

Fibromyalgia; Obesity

Interventions

Diet, Mediterranean

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Central Study Contacts

Alberto Sulli, Professor

CONTACT

010-35338710; alberto.sulli@unige.it

Livia Pisciotta, Professor

CONTACT

010-3538689; livia.pisciotta@unige.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: April 8, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be share upon publication in peer review journals.
• Access Criteria: Data will be uploaded on open access research repository and identified by a doi.

Locations

IT (1)