NCWS or IBS/FD in Relatives of CD Patients

NCT07584473 | Recruiting

• 1 other identifier: ACPM35
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 2

Brief Summary

Over 50% of non-celiac wheat sensitivity (NCWS) patients are HLA DQ2/DQ8 positive and often have a Celiac Disease (CD) family history. Studies have identified a subgroup of NCWS patients whose clinical and immunological features are closer to CD than to irritable bowel syndrome/functional dyspepsia (IBS/FD) ('inflammatory subgroup'). The investigators hypothesized that among CD patient's relatives, there might be a high number of NCWS subjects, who hypothetically belong to the 'inflammatory subgroup'. Therefore, the aim of this multi-step project is to identify the prevalence of both self-reported NCWS and IBS/FD not related to wheat ingestion among CD patient's relatives (parents, grandparents, siblings and sons).

Conditions

Non Celiac Wheat Sensitivity; IBS (Irritable Bowel Syndrome); Functional Dyspepsia; Celiac Disease

Keywords

non celiac wheat sensitivity; irritable bowel syndrome; functional dyspepsia; celiac disease; Relatives

Outcome Measures

Primary Outcomes (1)

• Identification of patients with self-reported NCWS or IBS/FD not related to wheat intake among relatives of CD patients: Gastrointestinal Symptom Rating Scale (GSRS)

  CD patient's relatives included in the study will refill out the following online questionnaire at the end of the 6-week long strict WFD (T2): - Gastrointestinal Symptom Rating Scale (GSRS) (range from 15 to 105) Patients reporting a reduction ≥30% in the questionnaire after WFD will be identified as patients with self-reported NCWS. Patients not reporting a reduction ≥30% in at least one questionnaire after WFD will be identified as patients with IBS/FD not related to wheat intake.

  From baseline to 6-week

Other Outcomes (4)

• Identification of patients with self-reported NCWS or IBS/FD not related to wheat intake among relatives of CD patients: Bristol Stool Scale

  From baseline to 6-week

• Identification of patients with self-reported NCWS or IBS/FD not related to wheat intake among relatives of CD patients: IBS-Symptom Severity Scale (IBS-SSS)

  From baseline to 6-week

• Identification of patients with self-reported NCWS or IBS/FD not related to wheat intake among relatives of CD patients: Extraintestinal Symptom Rating Scale (ESRS)

  From baseline to 6-week

Study Arms (1)

Six-week long strict Wheat-Free Diet

ACTIVE COMPARATOR

CD patient's first-degree relatives with IBS/FD-like and extraintestinal (EI) symptoms

Other: Wheat-Free Diet

Interventions

Wheat-Free Diet OTHER

Patients, identified at T1, will undergo a 6-week long strict WFD (preliminary dietician consul will be granted to all subjects), at the end of which (T2) they will fill-out an online form including a WFD adherence questionnaire (i.e. modified 'Biagi' score) and the questionnaires reported in WP1. Patients reporting a reduction ≥30% in at least one questionnaire after WFD will be identified as self-reported NCWS, all the others will be identified as IBS/FD not related to wheat intake.

Also known as: WFD

Six-week long strict Wheat-Free Diet

Eligibility Criteria

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

You may qualify if:

• CD patient's relatives
• \>18 years old
• reporting IBS/FD-like and extraintestinal (EI) symptoms

You may not qualify if:

• drug and/or alcohol (\>30 g/day for men and \>20 g/day for women) abuse;
• treatment with steroids and/or non-steroidal anti-inflammatory drugs in the 2 weeks before duodenal biopsy;
• pregnancy or breastfeeding;
• diagnosis of chronic inflammatory bowel disease or other organic pathologies affecting the digestive system \[e.g., IgE-mediated Wheat Allergy (WA), microscopic colitis, diverticulitis, segmental colitis associated with diverticulosis, etc.\], neurological diseases, major psychiatric disorders, infectious diseases, immunological deficiencies, and impairments limiting physical activity.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (2)

Celiac Disease and Food Intolerance Clinic, Geriatrics Unit, "P. Giaccone" University Hospital, Palermo

Palermo, PA, 90127, Italy

RECRUITING

Internal Medicine Unit, P.O. "V. Cervello," Ospedali Riuniti "Villa Sofia-Cervello," Palermo

Palermo, PA, 90146, Italy

RECRUITING

Related Publications (13)

• Biagi F, Bianchi PI, Marchese A, Trotta L, Vattiato C, Balduzzi D, Brusco G, Andrealli A, Cisaro F, Astegiano M, Pellegrino S, Magazzu G, Klersy C, Corazza GR. A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life. Br J Nutr. 2012 Nov 28;108(10):1884-8. doi: 10.1017/S0007114511007367. Epub 2012 Feb 10.

  PMID: 22321199 BACKGROUND

• Drossman DA, Hasler WL. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016 May;150(6):1257-61. doi: 10.1053/j.gastro.2016.03.035. No abstract available.

  PMID: 27147121 BACKGROUND

• Vaquero L, Rodriguez-Martin L, Alvarez-Cuenllas B, Hernando M, Iglesias-Blazquez C, Menendez-Arias C, Vivas S. Coeliac disease and gastrointestinal symptom screening in adult first-degree relatives. J Gastroenterol Hepatol. 2017 Dec;32(12):1931-1937. doi: 10.1111/jgh.13801.

  PMID: 28387454 BACKGROUND

• Troncone R, Greco L, Mayer M, Mazzarella G, Maiuri L, Congia M, Frau F, De Virgiliis S, Auricchio S. In siblings of celiac children, rectal gluten challenge reveals gluten sensitization not restricted to celiac HLA. Gastroenterology. 1996 Aug;111(2):318-24. doi: 10.1053/gast.1996.v111.pm8690196.

  PMID: 8690196 BACKGROUND

• Seidita A, Giuliano A, Soresi M, Chiavetta M, Nardi E, Mogavero G, Giannone G, Carroccio A, Mansueto P. Fecal calprotectin levels in patients with non-celiac wheat sensitivity: a proof of concept. Intern Emerg Med. 2024 Aug;19(5):1255-1266. doi: 10.1007/s11739-024-03595-7. Epub 2024 Apr 12.

  PMID: 38609737 BACKGROUND

• Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio F, Carteni M, Riegler G, de Magistris L, Fasano A. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med. 2011 Mar 9;9:23. doi: 10.1186/1741-7015-9-23.

  PMID: 21392369 BACKGROUND

• Mansueto P, Di Liberto D, Fayer F, Soresi M, Geraci G, Giannone AG, Seidita A, D'Alcamo A, La Blasca F, Lo Pizzo M, Florena AM, Dieli F, Carroccio A. TNF-alpha, IL-17, and IL-22 production in the rectal mucosa of nonceliac wheat sensitivity patients: role of adaptive immunity. Am J Physiol Gastrointest Liver Physiol. 2020 Sep 1;319(3):G281-G288. doi: 10.1152/ajpgi.00104.2020. Epub 2020 Jul 13.

  PMID: 32658621 BACKGROUND

• Esteve M, Rosinach M, Fernandez-Banares F, Farre C, Salas A, Alsina M, Vilar P, Abad-Lacruz A, Forne M, Marine M, Santaolalla R, Espinos JC, Viver JM. Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis. Gut. 2006 Dec;55(12):1739-45. doi: 10.1136/gut.2006.095299. Epub 2006 May 18.

  PMID: 16709658 BACKGROUND

• Di Liberto D, Mansueto P, D'Alcamo A, Lo Pizzo M, Lo Presti E, Geraci G, Fayer F, Guggino G, Iacono G, Dieli F, Carroccio A. Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet. Clin Transl Gastroenterol. 2016 Jul 7;7(7):e178. doi: 10.1038/ctg.2016.35.

  PMID: 27388423 BACKGROUND

• Carroccio A, Rini G, Mansueto P. Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity. Gastroenterology. 2014 Jan;146(1):320-1. doi: 10.1053/j.gastro.2013.08.061. Epub 2013 Nov 22. No abstract available.

  PMID: 24275240 BACKGROUND

• Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907. doi: 10.1038/ajg.2012.236. Epub 2012 Jul 24.

  PMID: 22825366 BACKGROUND

• Brottveit M, Beitnes AC, Tollefsen S, Bratlie JE, Jahnsen FL, Johansen FE, Sollid LM, Lundin KE. Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity. Am J Gastroenterol. 2013 May;108(5):842-50. doi: 10.1038/ajg.2013.91. Epub 2013 Apr 16.

  PMID: 23588237 BACKGROUND

• Araya M, Oyarzun A, Lucero Y, Espinosa N, Perez-Bravo F. DQ2, DQ7 and DQ8 Distribution and Clinical Manifestations in Celiac Cases and Their First-Degree Relatives. Nutrients. 2015 Jun 18;7(6):4955-65. doi: 10.3390/nu7064955.

  PMID: 26096569 BACKGROUND

Related Links

• PubMed

MeSH Terms

Conditions

Irritable Bowel Syndrome; Celiac Disease

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Malabsorption Syndromes; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Antonio Carroccio, MD

  University of Palermo

  STUDY DIRECTOR

Central Study Contacts

Pasquale Mansueto, MD

CONTACT

+393477279879; pasquale.mansueto@unipa.it

Aurelio Seidita, MD

CONTACT

aurelio.seidita@unipa.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2026
• First Posted: May 13, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)