Can Gluten/Wheat or Other Foods be Responsible for FMF Attacks

NCT06338891 | Recruiting

• 1 other identifier: ACPM34
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Familial Mediterranean Fever (FMF) is a chronic hereditary autoinflammatory disease caused by mutations in the MEditerranean FeVer (MEFV) gene which codes for pyrin. Dysfunction of this protein determines an inappropriate response to inflammatory stimuli. The clinical course of the disease is characterized by recurrent episodes of fever and inflammation of the serous membranes, which manifest with chest, abdominal and joint pain. Several studies suggest a possible association between acute FMF attacks and dietary triggers, including wheat. However, it is still unclear to what extent wheat is responsible for the reactivation of FMF and if, between one acute attack and another, patients with FMF experience other symptoms, both gastrointestinal and extraintestinal, characteristic of gluten/wheat sensitivity not linked to celiac disease or immunoglobulin E (IgE)-mediated wheat allergy (i.e. Non-Celiac Wheat Gluten/Sensitivity, NCGS/NCWS). Therefore, this study aims to evaluate the appearance of symptoms compatible with an acute attack of FMF following the ingestion of wheat or other foods, and the prevalence of self-perceived gluten/wheat sensitivity in patients with FMF.

Conditions

Familial Mediterranean Fever; Non-celiac Gluten Sensitivity

Keywords

Familial Mediterranean Fever; Non-celiac Gluten Sensitivity

Outcome Measures

Primary Outcomes (3)

• Prevalence of the self-perception of wheat as a potential trigger of acute attack in patients with familial Mediterranean fever (FMF)

  To determine the prevalence of the self-perception of wheat as a potential trigger of acute attack in patients with FMF, defined as the appearance of symptoms and signs compatible with FMF flare-up following wheat intake.

  From May 2024 to May 2025

• Prevalence of the self-perception of other foods, other than wheat, as potential triggers of an acute attack in patients with FMF

  To determine the prevalence of the self-perception of other foods, other than wheat, as potential triggers of an acute attack in patients with FMF, defined as the appearance of symptoms and signs compatible with a flare-up of FMF following the intake of these specific foods, other than wheat.

  From May 2024 to May 2025

• Prevalence of self-reported NCGS/NCWS in patients with FMF

  To determine the prevalence of self-reported NCGS/NCWS in patients with FMF, defined as the appearance of gastrointestinal and extraintestinal symptoms and signs secondary to gluten/wheat ingestion, compatible with the clinical manifestations of NCGS/NCWS and not identifiable, by the patient, as FMF flare-ups, compared to a control group.

  From May 2024 to May 2025

Secondary Outcomes (42)

• Genetic differences between FMF patients who perceive a trigger effect of wheat and those who do not identify this specific food as a potential trigger of the disease flares.

  From May 2024 to May 2025

• Genetic differences between FMF patients who perceive a trigger effect of foods other than wheat and those who do not identify foods other than wheat as a potential trigger of disease flares.

  From May 2024 to May 2025

• Genetic differences between patients with FMF who self-report NCGS/NCWS and those who do not self-report it.

  From May 2024 to May 2025

• Ethnic group differences between FMF patients who perceive a trigger effect of wheat and those who do not identify this specific food as a potential trigger of the disease flares.

  From May 2024 to May 2025

• Ethnic group differences between FMF patients who perceive a trigger effect of foods other than wheat and those who do not identify foods other than wheat as a potential trigger of disease flares.

  From May 2024 to May 2025

Study Arms (2)

FMF patients

Patients, of both sexes, aged between 6 months and 80 years, affected by FMF, classified according to the Eurofever/PRINTO criteria

Other: Main questionnaire; Other: Secondary questionnaire

Control subjects

Subjects of the vaccination center of the University Hospital 'Paolo Giaccone'" of Palermo, Italy

Other: Secondary questionnaire

Interventions

Main questionnaire OTHER

Main questionnaire will evaluate the demographic and genetic characteristics, clinical manifestations, and self-perception of sensitivity to wheat or other food and the possible relationship between the intake of wheat or other foods and the flare-ups of the disease in FMF patients

FMF patients

Secondary questionnaire OTHER

Secondary questionnaire will investigate the possible appearance of gastrointestinal and extraintestinal symptoms linked to the ingestion of gluten/wheat, which are not identifiable, by the patient, as FMF flare-ups, but might be compatible with a NCGS/NCWS diagnosis

Control subjects; FMF patients

Eligibility Criteria

• Age: 6 Months - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of FMF will be enrolled in four Italian centers: the "Ambulatorio di Celiachia ed Intolleranze Alimentari" of "Azienda Ospedaliera Universitaria Policlinico (AOUP) 'Paolo Giaccone'", Palermo, Italy, the Internal Medicine Unit of "Azienda Ospedaliera 'Ospedali Riuniti Villa Sofia-Cervello'", Palermo, Italy, the "Centro di Riferimento per le Malattie Autoinfiammatorie e per le Malattie Lisosomiali" and the "Unità Malattie Rare, Centro Ricerca sulle Febbri Periodiche" of "Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS", Rome, Italy. Patients will be asked to reposnd to a main questionnaire, to evaluate the patient's demographic, clinical and genetic characteristics, and the perception of a link between FMF exacerbations and intake of wheat or other foods, and, in patients with self-reported NCGS/NCWS, gastrointestinal and extraintestinal manifestations related to gluten/wheat intake will be investigated using a further secondary questionnaire.

You may qualify if:

• Patients, of both sexes, aged between 6 months and 80 years, affected by FMF, classified according to the Eurofever/PRINTO criteria.
• Patients able to understand and complete the questionnaires independently (or, in the case of pediatric ones, analyzed through the answers provided by parents).

You may not qualify if:

• Patients aged \<6 months and \>80 years.
• Patients unable to provide informed consent or complete the questionnaires.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (1)

University Hospital of Palermo

Palermo, Sicily, 90127, Italy

RECRUITING

Related Publications (13)

• Carroccio A, Mansueto P, Soresi M, Fayer F, Di Liberto D, Monguzzi E, Lo Pizzo M, La Blasca F, Geraci G, Pecoraro A, Dieli F, Schuppan D. Wheat Consumption Leads to Immune Activation and Symptom Worsening in Patients with Familial Mediterranean Fever: A Pilot Randomized Trial. Nutrients. 2020 Apr 17;12(4):1127. doi: 10.3390/nu12041127.

  PMID: 32316660 BACKGROUND

• Demir A, Akyuz F, Gokturk S, Evirgen S, Akyuz U, Ormeci A, Soyer O, Karaca C, Demir K, Gundogdu G, Gulluoglu M, Erer B, Kamali S, Kaymakoglu S, Besisik F, Gul A. Small bowel mucosal damage in familial Mediterranean fever: results of capsule endoscopy screening. Scand J Gastroenterol. 2014 Dec;49(12):1414-8. doi: 10.3109/00365521.2014.976838. Epub 2014 Nov 5.

  PMID: 25369738 BACKGROUND

• Deshayes S, Fellahi S, Bastard JP, Launay JM, Callebert J, Fraisse T, Buob D, Boffa JJ, Giurgea I, Dupont C, Jegou S, Straube M, Karras A, Aouba A, Grateau G, Sokol H, Georgin-Lavialle S; AA Amyloidosis Study Group; AA amyloidosis Study Group. Specific changes in faecal microbiota are associated with familial Mediterranean fever. Ann Rheum Dis. 2019 Oct;78(10):1398-1404. doi: 10.1136/annrheumdis-2019-215258. Epub 2019 Aug 3.

  PMID: 31377728 BACKGROUND

• Ekinci RMK, Balci S, Bisgin A, Cetin FT, Tumgor G. The contribution of diet preference to the disease course in children with familial Mediterranean fever: a cross-sectional study. Reumatologia. 2020;58(2):81-86. doi: 10.5114/reum.2020.95361. Epub 2020 Apr 30.

  PMID: 32476680 BACKGROUND

• Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO). Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis. 2019 Aug;78(8):1025-1032. doi: 10.1136/annrheumdis-2019-215048. Epub 2019 Apr 24.

  PMID: 31018962 BACKGROUND

• Leccioli V, Oliveri M, Romeo M, Berretta M, Rossi P. A New Proposal for the Pathogenic Mechanism of Non-Coeliac/Non-Allergic Gluten/Wheat Sensitivity: Piecing Together the Puzzle of Recent Scientific Evidence. Nutrients. 2017 Nov 2;9(11):1203. doi: 10.3390/nu9111203.

  PMID: 29099090 BACKGROUND

• Mansueto P, Seidita A, Chiavetta M, Genovese D, Giuliano A, Priano W, Carroccio A, Casuccio A, Amodio E. Familial Mediterranean Fever and Diet: A Narrative Review of the Scientific Literature. Nutrients. 2022 Aug 5;14(15):3216. doi: 10.3390/nu14153216.

  PMID: 35956392 BACKGROUND

• Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr. 2014;33(1):39-54. doi: 10.1080/07315724.2014.869996.

  PMID: 24533607 BACKGROUND

• MELLINKOFF SM, SCHWABE AD, LAWRENCE JS. A dietary treatment for familial Mediterranean fever. Arch Intern Med. 1961 Jul;108:80-5. doi: 10.1001/archinte.1961.03620070082010. No abstract available.

  PMID: 13769243 BACKGROUND

• Schwabe AD, Peters RS. Familial Mediterranean Fever in Armenians. Analysis of 100 cases. Medicine (Baltimore). 1974 Nov;53(6):453-62. doi: 10.1097/00005792-197411000-00005. No abstract available.

  PMID: 4437392 BACKGROUND

• Uhde M, Ajamian M, Caio G, De Giorgio R, Indart A, Green PH, Verna EC, Volta U, Alaedini A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016 Dec;65(12):1930-1937. doi: 10.1136/gutjnl-2016-311964. Epub 2016 Jul 25.

  PMID: 27459152 BACKGROUND

• Verrecchia E, Sicignano LL, La Regina M, Nucera G, Patisso I, Cerrito L, Montalto M, Gasbarrini A, Manna R. Small Intestinal Bacterial Overgrowth Affects the Responsiveness to Colchicine in Familial Mediterranean Fever. Mediators Inflamm. 2017;2017:7461426. doi: 10.1155/2017/7461426. Epub 2017 Dec 12.

  PMID: 29379228 BACKGROUND

• Yenokyan G, Armenian HK. Triggers for attacks in familial Mediterranean fever: application of the case-crossover design. Am J Epidemiol. 2012 May 15;175(10):1054-61. doi: 10.1093/aje/kwr460. Epub 2012 Jan 10.

  PMID: 22234484 BACKGROUND

MeSH Terms

Conditions

Familial Mediterranean Fever

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Antonio Carroccio, MD

  University of Palermo

  STUDY DIRECTOR

Central Study Contacts

Pasquale Mansueto, MD

CONTACT

3477279879; pasquale.mansueto@unipa.it

Aurelio Seidita, MD

CONTACT

3209150370; aurelio.seidita@unipa.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: April 1, 2024
• Study Start: May 1, 2024
• Primary Completion: August 30, 2024
• Study Completion: May 1, 2026
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

IT (1)