Wheat-free Diet in the Treatment of Sjogren's Syndrome

NCT05644795 | Completed

• 1 other identifier: ACPM31
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

Recent data show that some foods can increase intestinal mucosa permeability and immune activation of subjects with gastrointestinal (GI) symptoms. Wheat seems the most frequent food which activates this inflammatory response and can cause both GI and extra-intestinal symptoms. Patients suffering from wheat-related troubles, in absence of celiac disease diagnosis, can suffer from non-celiac wheat sensitivity (NCWS) and our previous studies showed that about 25% of them are also affected by autoimmune diseases (AD). A gluten-free diet (GFD) can influence inflammatory pattern of AD, including Sjogren's syndrome (SS). Thus, the investigators would enquire if SS patients may also suffer from NCWS and how a wheat-free diet (WFD) modifies their clinical features, and inflammatory and cytokine pattern. The investigators will also assess how wheat reintroduction, by an open challenge, modifies their clinical parameters, intestinal permeability, and both local and systemic inflammatory response.

Conditions

Sjogren's Syndrome; Non-celiac Gluten Sensitivity

Keywords

Sjogren's Syndrome; Non-celiac Gluten Sensitivity; Non-celiac Wheat Sensitivity

Outcome Measures

Primary Outcomes (5)

• Self-perceived non-celiac wheat sensitivity (NCWS) questionnaire in SS patients

  To identify SS patients reporting a self-perceived NCWS; all patients will be asked to answer, consecutively, to a validated questionnaire for the self-assessment of wheat and other foods' intolerance. This is a questionnaire self-compiled by patients consisting of three sections: 1) general information (eg. age, sex, highest completed education level, etc.) 2) wheat-related symptoms (sore 0 = no symptoms, score = 1, symptoms after wheat intake; if score = 1 other question qualitatively inquire the symptoms evoked by wheat intake, eg. what kind of symptoms, how long patient perceive this problem, etc.); 3) other foods-related symptoms (score 0 = no symptoms, score 1 = symptoms after intake of other foods; if score = 1 other question qualitatively inquire the symptoms evoked by the intake of the specific food reported by the patients, eg. what kind of symptoms, how long patient perceive this problem, etc.)

  Before enter the study

• Effect of WFD plus CMPFD in symptoms of SS patients as assessed by ESSPRI

  To define effects induced by a WFD plus CMPFD in SS patient's symptoms. The following score will be used: European League Against Rheumatism (EULAR) SS Patient Reported Index \[ESSPRI, a self-evaluation index measuring symptoms, including pain, fatigue, and dryness, each symptom measured with a single 0, no symptoms, to 10, severe symptoms, scores \<5 indicating low and \>5 high disease activity).

  From the start of the study (T0) to 2 months of wheat elimination diet (T1).

• Effect of WFD plus CMPFD in symptoms of SS patients as assessed by ESSDAI

  To define effects induced by a WFD plus CMPFD in SS patient's symptoms. The following score will be used: EULAR SS Disease Activity Index (ESSDAI, a systemic disease activity index, consisting of 12 domains, 11 related to organ involvement and 1 biological domain, cut-off values of \>5 and \<14 defining moderate, and \>14 severe systemic disease activity).

  From the start of the study (T0) to 2 months of wheat elimination diet (T1).

• Effect of WFD plus CMPFD in symptoms of SS patients as assessed by GSRS

  To define effects induced by a WFD plus CMPFD in SS patient's symptoms. The following score will be used: Gastrointestinal Symptom Rating Scale (GSRS), assessment scale for irritable bowel syndrome-like and functional dyspepsia-like symptoms, providing for a score ranging from 15 (no gastrointestinal symptoms) to 60 (uncontrolled gastrointestinal symptoms).

  From the start of the study (T0) to 2 months of wheat elimination diet (T1).

• Effect of WFD plus CMPFD in symptoms of SS patients as assessed by Extraintestinal symptoms rating scale.

  To define effects induced by a WFD plus CMPFD in SS patient's symptoms. The following score will be used: Extraintestinal symptoms rating scale, a scoring system based on the symptoms most frequently observed in NCWS patients, providing for a score ranging from 9 (no extra intestinal symptoms) to 34 (uncontrolled extra intestinal symptoms).

  From the start of the study (T0) to 2 months of wheat elimination diet (T1).

Secondary Outcomes (45)

• Effect of open wheat challenge in symptoms of SS patients as assessed by ESSPRI.

  From T1 to 2 weeks of open wheat challenge (T2int and T3con).

• Effect of open wheat challenge in symptoms of SS patients as assessed by ESSDAI.

  From T1 to 2 weeks of open wheat challenge (T2int and T3con).

• Effect of open wheat challenge in symptoms of SS patients as assessed by GSRS.

  From T1 to 2 weeks of open wheat challenge (T2int and T3con).

• Effect of open wheat challenge in symptoms of SS patients as assessed by Extraintestinal symptoms rating scale.

  From T1 to 2 weeks of open wheat challenge (T2int and T3con).

• Salivary flux

  From the start of the study (T0) to 2 months of wheat elimination diet (T1), to 2 weeks of open wheat challenge (T2int and T3con).

Study Arms (2)

Active Comparator: wheat/milk free diet (W/MFD) group

ACTIVE COMPARATOR

Patients randomized to intervention group will go to a 2 months elimination diet (wheat and cow's milk products). After 2 months of elimination diet they will go to an open challenge, with reintroduction of wheat. After 2 weeks of open diet or whenever rheumatologic, intestinal and/or extraintestinal symptoms should return or intensify, patients will end the study.

Dietary Supplement: Wheat/milk free diet (W/MFD) group

Placebo Comparator: rice/turkey free diet (R/TFD) group

PLACEBO COMPARATOR

Patients randomized to control group will go to a 2 months elimination diet (rice and turkey's meat). After 2 months of elimination diet they will crossover to a 2 months elimination diet (wheat and cow's milk products). After 2 months of elimination diet they will go to an open challenge, with reintroduction of wheat. After 2 weeks of open diet or whenever rheumatologic, intestinal and/or extraintestinal symptoms should return or intensify, patients will end the study.

Dietary Supplement: Rice/turkey free diet (R/TFD) group

Interventions

Wheat/milk free diet (W/MFD) group DIETARY_SUPPLEMENT

Patients randomized to intervention diet group will have to follow a wheat and cow's milk products free diet and, after 2 months, they will be exposed to an open wheat challenge, with reintroduction of wheat. After 2 weeks of open diet, or whenever dermatologic, intestinal and/or extraintestinal symptoms should return or intensify, all patients will be revaluated and will end the study.

Also known as: Intervention Group

Active Comparator: wheat/milk free diet (W/MFD) group

Rice/turkey free diet (R/TFD) group DIETARY_SUPPLEMENT

Patients randomized to control diet group will have to follow a diet with elimination of rice and turkey's meat products for 2 months; after that they will crossover to a wheat and cow's milk products free diet and, finally, after 2 months, they will be exposed to an open wheat challenge, with reintroduction of wheat. After 2 weeks of open diet, or whenever dermatologic, intestinal and/or extraintestinal symptoms should return or intensify, all patients will be revaluated and will end the study.

Also known as: Control Group

Placebo Comparator: rice/turkey free diet (R/TFD) group

Eligibility Criteria

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

You may qualify if:

• age \>18 and \<65 years;
• negativity of anti-deamidated gliadin protein (anti-DGP) immunoglobulins (Ig) class A (IgA) and immunoglobulins (Ig)G, anti-tissue transglutaminase (anti-tTG) class IgA and IgG, and Endomysium antibodies (EmA);
• absence of intestinal villous atrophy, documented in all the patients carrying the DQ2 and/or the DQ8 Human Leukocyte Antigen (HLA) haplotypes (thus irrespective of CD-specific serum antibody negativity
• absence of WA (negative prick-test and/or specific serum immunoglobulin (Ig) E assay for wheat, gluten, and gliadin).

You may not qualify if:

• age \<18 and \>65 years;
• pregnancy;
• alcohol and/or drug abuse;
• Helicobacter pylori and other bacterial and/or parasitic infections;
• diagnosis of chronic inflammatory bowel disease and other organic pathology affecting the digestive system (e.g., severe liver disease), nervous system diseases, major psychiatric disorders, immunological deficits, and impairments that limit physical activity;
• diagnosis of cancer
• patients undergoing chemotherapy and/or radiotherapy.
• Study design In a preliminary phase of the study, all patients who access the SS outpatient clinic of the Rheumatology Department of the University Hospital 'P. Giaccone' of Palermo, Italy, will be asked to answer, consecutively, to a questionnaire for the self-assessment of wheat and other foods' intolerance.
• After this evaluation, individual's enrollment will start. A database will be predisposed to register demographic, clinical, laboratory, cytofluorimetric and immunohistochemistry data. A repository bank will be used to collect samples from patients at different timepoints.
• Before starting the elimination diet (at time 0, T0), patients will be evaluated by experienced rheumatologists to assess their clinical features, as well as by physicians with expertise in the field of food intolerance about GI and extraintestinal symptoms which could be related to foods intake. Moreover, at this time point, all subjects will be subjected to:
• salivary flux study, by standard sialometry, and salivary samples collection (treated to block enzymatic digestion of proteins), to dose immunologic and inflammatory markers;
• a blood sample, for the analysis of inflammatory markers, cytokine profile, and intestinal permeability markers;
• a urine collection, after the administration of the lactulose/mannitol (LA/MA) test, to define intestinal permeability;
• a collection of stools, for calprotectin assay and definition of the gut microbiota;
• a dietary consult to better explain the dietary approach and provide any information useful to allow adherence to the elimination diet;

Sponsors & Collaborators

• Aurelio Seidita: collaborator
• University of Palermo: lead

Study Sites (3)

Internal Medicine Department of the University Hospital of Palermo

Palermo, Palermo, 90127, Italy

Location

Rheumatology Department of the University Hospital of Palermo

Palermo, PA, 90127, Italy

Location

Internal Medicine Division of the "Cervello-Villa Sofia" Hospital

Palermo, PA, 90146, Italy

Location

Related Publications (6)

• Carroccio A, Giambalvo O, Blasca F, Iacobucci R, D'Alcamo A, Mansueto P. Self-Reported Non-Celiac Wheat Sensitivity in High School Students: Demographic and Clinical Characteristics. Nutrients. 2017 Jul 19;9(7):771. doi: 10.3390/nu9070771.

  PMID: 28753927 RESULT

• 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 RESULT

• 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 RESULT

• Fasano S, Mauro D, Macaluso F, Xiao F, Zhao Y, Lu L, Guggino G, Ciccia F. Pathogenesis of primary Sjogren's syndrome beyond B lymphocytes. Clin Exp Rheumatol. 2020 Jul-Aug;38 Suppl 126(4):315-323. Epub 2020 Oct 23.

  PMID: 33095148 RESULT

• Rizzo C, Grasso G, Destro Castaniti GM, Ciccia F, Guggino G. Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation. Vaccines (Basel). 2020 Jun 3;8(2):272. doi: 10.3390/vaccines8020272.

  PMID: 32503132 RESULT

• Rizzo C, La Barbera L, Lo Pizzo M, Ciccia F, Sireci G, Guggino G. Invariant NKT Cells and Rheumatic Disease: Focus on Primary Sjogren Syndrome. Int J Mol Sci. 2019 Oct 31;20(21):5435. doi: 10.3390/ijms20215435.

  PMID: 31683641 RESULT

MeSH Terms

Conditions

Sjogren's Syndrome

Interventions

Population Groups; Control Groups

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Antonio Carroccio, MD

  University of Palermo

  STUDY CHAIR

• Giuliana Guggino, MD

  University of Palermo

  STUDY CHAIR

Study Design

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

Model Details: Prospective, randomized, placebo-controlled, cross-over, single center clinical trials.

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: December 9, 2022
• Study Start: January 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: January 30, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)