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AzTrials

Sjogren's SyndromeNCT05644795

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

A study testing Wheat/milk free diet (W/MFD) group and Rice/turkey free diet (R/TFD) group in people with Sjogren's Syndrome and Non-celiac Gluten Sensitivity, run by University of Palermo at 3 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Wheat/milk free diet (W/MFD) group and Rice/turkey free diet (R/TFD) group
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
3 sitesItaly
Study dates
1 Jan 2023to 30 Jan 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • age <18 and >65 years;
  • self-exclusion of gluten/wheat from the diet and refusal to reintroduce it, for diagnostic purposes, before entering the study;
  • 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;
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  • 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.
  • Patients enrolled based on the inclusion and exclusion criteria and who have agreed to enter the study, after having signed the informed consent, will be randomized, matched for age/gender/racial origin, through a computerized system into an intervention group and a control group. The two groups, each of 15 subjects, will be asked to follow a diet for 2 months. Intervention group will be asked to eliminate wheat and all cow's milk (both fresh and aged) products from the diet (i.e., WFD plus CMPFD). The control group will be asked to eliminate rice and turkey's meat products from the diet. The elimination diet in the control group must be considered as a 'placebo diet' because both rice and turkey's meat are foods known to be used in standard 'oligoantigenic' elimination diet.
  • 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;
  • finally, an alimentary (for the self-assessment of adherence to the diet) and symptom's diary will be provided to all patients, which must be filled-in daily.
  • After 2 months of elimination diet (at time 1, T1), intervention and control patients will be evaluated again both clinically and by laboratory techniques, repeating exactly what have been done at T0. Moreover, they will have to deliver alimentary and symptom's diary, and will discuss the results with physicians.
  • At this time-point, the subjects enrolled in the intervention group 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 (T2int), patients will be valued again both clinically and by laboratory techniques, repeating exactly what have been done at T0 and T1. Patients in this group will end the study at this time-point.
  • At the same timepoint, patients enrolled in the control group will be asked to repeat the elimination diet, this time removing from the diet wheat and all cow's milk (both fresh and aged) products (i.e., i.e., WFD plus CMPFD, in the context of a cross-over design), for further 2 months (T2con). At the end of these 2 months patients will be valued again both clinically and by laboratory techniques repeating exactly what have been done at T0 and T1. As described before for the intervention group, at this time-point patients of the control group 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 (T3con), patients will be valued again both clinically and by laboratory techniques repeating exactly what have been done at T0, T1 and T2con. Patients in this group will end the study at this time-point.
  • Sample size The sample size is difficult to determine as no precise data are known about the effectiveness of a WFD and the response to wheat re-exposure after challenge in SS patients, as well as NCWS frequency in these subjects; previously reported data suggest that about 25% of NCWS patients suffer from an autoimmune disease, and in a study evaluating the effect of a GFD on quality of life, GI symptoms, and immune system in patients with fibromyalgia and NCWS, statistical significance was reached with 10 subjects. Other studies assessing NCWS immunological pattern obtained statistical significance with 26, 30, 22, and 12 patients. Therefore, considering the nature of this prospective and pilot study the investigators planned to enroll a total of 30 patients suffering from SS, 15 with GI symptoms and 15 without, fulfilling the American-European Consensus Group criteria for SS.
  • Definition of 'positivity' to the open challenge During the open challenge period, patients will be asked to note the possible onset of intestinal and/or extraintestinal symptoms using the food and symptom's diary, using a 10-point Visual Analogic Scale (VAS). The challenges will be stopped when a clinical reaction will occur for at least two consecutive days with a >3-point increase in the patient's recorded symptom VAS scale. The challenges will be considered positive if the same symptoms, which were initially present, will reappear after their disappearance on elimination diet and if the GSRS score and/or the extraintestinal symptoms rating scale will be 25% higher than the same score recorded on elimination diet. Finally, from a strictly rheumatologic point of view, the challenge will be considered positive if a 5% increase in the ESSPRI and ESSDAI score will be registered compared to the same score recorded on the elimination diet.
  • Statistical Analysis Statistical analysis will be performed using commercial software. Parametric and non-parametric statistical analysis will be performed calculating the mean ± standard deviation (SD) and median, respectively. For comparison of parametric and non-parametric data, the t-test and Mann-Whitney rank-sum test will be used where appropriate. Spearman's correlation analysis will be used to quantify the association between analysed variables. Data will be expressed as mean ± SD. P values less than 0.05 will be considered significant.
  • All subjects will agree to participate in the study. The study protocol will conform to the ethical guidelines of the Declaration of Helsinki, will be preliminary approved by the Human Research committee of the University Hospital of Palermo, Italy, and registered on the CliniaclTrials.gov. All authors will have access to the study data and will review and approve the final manuscript.

Trial locations and contacts

3 sites in 1 country.

Italy3 sites

  • Internal Medicine Department of the University Hospital of Palermo

    Palermo, Palermo, 90127

  • Rheumatology Department of the University Hospital of Palermo

    Palermo, PA, 90127

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

    Palermo, PA, 90146

Other trials in Italy

About this study

Official title: Efficacy of a Wheat-free Diet in Autoimmune Diseases: a Pilot Therapeutic Study in Sjogren's Disease

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.

Read the detailed description

In recent years, the existence of a wheat-related disorder, in patients who do not suffer from celiac disease (CD) or wheat allergy (WA), has been definitively ascertained and defined as non-celiac wheat sensitivity (NCWS). Its prevalence in the general population is unknown but self-reported NCWS is around 10%. Conflicting data have been reported about the underlying physiopathology. It has been known for years how exposure to gliadin, both in CD and in healthy patients (albeit with reduced levels in the latter), is able to alter intestinal permeability acting on zonulin release and signalling mechanisms. More recently, it has been shown that wheat has high concentrations of wheat amylase-trypsin inhibitors (ATIs), proteins able to activate innate immunity via toll-like receptor-4 (TLR-4) on myeloid cells. Orally ingested ATIs increase intestinal inflammation by activating gut and mesenteric lymphnode myeloid cells.

An increasing number of data have shown that patients with NCWS could have an association with autoimmune diseases, including thyroiditis, undifferentiated connective tissue disease, psoriatic arthritis, spondylarthritis, and Sjogren's syndrome (SS).

SS is an autoimmune disease characterized by an infiltrate of mononuclear cells, mainly lymphocytes, in the exocrine glands, especially the salivary and lacrimal glands. Some preliminary data suggested that a GFD can reduce sialadenitis and increase salivary flow in SS and CD patients. Furthermore, some SS patients have an inflammatory response (release of nitric oxide) to a rectal gluten challenge.

Based on these evidences, as well as on the ability of gluten/wheat to increase intestinal permeability, altering zonulin mechanisms of regulation and signalling, and the ability of some of its components (ATIs, but not only) to activate a local inflammatory response, it could be hypothesized that gluten/wheat may represents one of the pathogenetic environmental factors of SS and that its intake may be able to worsen symptoms in affected patients. In our hypothesis, exposure to gluten/wheat would cause a release of zonulin, which, binding to the surface of the intestinal epithelial cells, is able to modify cell cytoskeleton and to cause the loss of normal occludins function, ultimately leading to an increased monolayer permeability. This increase in permeability would result in greater exposure of the immune system cells to gluten/wheat molecules via activation of TLR-4, with an increase in the infiltration and activation of myeloid cells in the intestinal mucosa and an augmented activity of lymphnode dendritic cells. Such local inflammatory response would have systemic repercussions with alteration of normal cytokine pattern and infiltration of monocytes/macrophages and T cells in the salivary and lacrimal glands, thus being able to contribute, as an environmental factor, to the onset and exacerbation of the clinical manifestations of SS.

Therefore, the investigators hypothesize that a wheat-free diet (WFD) can reduce the inflammatory state and ameliorate the clinical symptoms in SS patients. This hypothesis will be evaluated in both SS patients with associate GI symptoms and in those without GI symptoms. The successive clinical and immunologic reaction to the re-exposure to wheat ingestion, performed by an open challenge, will be also evaluated to confirm a wheat-dependent mechanism and to understand the underlining mechanisms. The project results will provide data about a possible therapeutic role of a WFD in SS and will improve the knowledges about the axis between the intestinal permeability and the systemic inflammation in SS.

More specifically, the investigators aim to:

  • identify the prevalence of self-reported NCWS in SS patients;
  • assess the overall effect that a WFD plus cow's milk products free diet (CMPFD) determines in symptoms control of the patients affected with SS; the investigators decided to include a CMPFD in association with a WFD because, according to several authors, including our previous studies, NCWS, and more generally gluten-related disorders, are often associated with multiple foods intolerance, first of all cow's milk products intolerance;
  • evaluate, by an open wheat challenge, the real frequency of a coexistent NCWS condition;
  • assess the possible role played by wheat ingestion in the pathogenesis and molecular mechanisms of SS and NCWS by analysing the variation of intestinal permeability and gut microbiota, in association with cytokines and lymphocytes pattern typical of SS.
Being tested
Wheat/milk free diet (W/MFD) group, Rice/turkey free diet (R/TFD) group
Keywords
Sjogren's Syndrome, Non-celiac Gluten Sensitivity, Non-celiac Wheat Sensitivity
Medical subject headings
Sjogren's Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Wheat/milk free diet (W/MFD) groupDietary supplement

    Also called Intervention Group

    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.

  • Rice/turkey free diet (R/TFD) groupDietary supplement

    Also called Control Group

    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.

Study groups in NCT05644795
Study groupRoleWhat they receive
Active Comparator: wheat/milk free diet (W/MFD) groupActive comparatorPatients 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.
Receives: Dietary Supplement: Wheat/milk free diet (W/MFD) group
Placebo Comparator: rice/turkey free diet (R/TFD) groupPlacebo comparatorPatients 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.
Receives: Dietary Supplement: Rice/turkey free diet (R/TFD) group

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.)

    Measured: Before enter the study

  2. 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).

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

  3. 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).

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

  4. 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).

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

  5. 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).

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

Secondary outcomes (45)

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

    To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in SS patients, both of the intervention group (T2int) and the control group (T3con). 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).

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

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

    To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in SS patients, both of the intervention group (T2int) and the control group (T3con). 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).

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

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

    To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in SS patients, both of the intervention group (T2int) and the control group (T3con). 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).

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

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

    To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in SS patients, both of the intervention group (T2int) and the control group (T3con). 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).

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

  5. Salivary flux

    Salivary flux (ml/min) will be studied by standard sialometry.

    Measured: 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).

  6. Salivary dosage of immunoglobulin A

    Laboratory salivary analysis will be performed to assess immunoglobulin A.

    Measured: 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).

  7. Salivary dosage of immunoglobulin G

    Laboratory salivary analysis will be performed to assess immunoglobulin G

    Measured: 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).

  8. Salivary dosage of lactoferrin

    Laboratory salivary analysis will be performed to assess lactoferrin.

    Measured: 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).

  9. Salivary dosage of beta 2-microglobulin

    Laboratory salivary analysis will be performed to assess beta 2-microglobulin.

    Measured: 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).

  10. Salivary dosage of IL-2

    Laboratory salivary analysis will be performed to assess interleukin (IL)-2

    Measured: 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).

  11. Salivary dosage of IL-6

    Laboratory salivary analysis will be performed to assess interleukin (IL)-6.

    Measured: 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).

  12. Laboratory blood analysis in SS and NCWS patients to assess ESR

    Laboratory blood analysis will be performed to assess erythrocyte sedimentation rate (ESR).

    Measured: 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).

  13. Laboratory blood analysis in SS and NCWS patients to assess CRP

    Laboratory blood analysis will be performed to assess C-reactive protein (CRP).

    Measured: 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).

  14. Laboratory blood analysis in SS and NCWS patients to assess RF.

    Laboratory blood analysis will be performed to assess rheumatoid factor (RF).

    Measured: 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).

  15. Laboratory blood analysis in SS and NCWS patients to assess C3

    Laboratory blood analysis will be performed to assess C3

    Measured: 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).

  16. Laboratory blood analysis in SS and NCWS patients to assess C4.

    Laboratory blood analysis will be performed to assess C4.

    Measured: 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).

  17. Laboratory blood analysis in SS and NCWS patients to assess complete blood count.

    Laboratory blood analysis will be performed to assess complete blood count.

    Measured: 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).

  18. Laboratory blood analysis in SS and NCWS patients to assess beta 2-microglobulin.

    Laboratory blood analysis will be performed to assess beta 2-microglobulin.

    Measured: 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).

  19. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: IL-6

    Measured: 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).

  20. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: IL-10

    Measured: 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).

  21. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: IL-17

    Measured: 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).

  22. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: IL-18

    Measured: 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).

  23. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: IL-21

    Measured: 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).

  24. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: IL-22

    Measured: 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).

  25. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: tumor necrosis factor (TNF)-alpha

    Measured: 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).

  26. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interferon (IFN)-gamma,

    Measured: 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).

  27. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: B cell activating factor (BAF)

    Measured: 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).

  28. Peripheral blood ELISA analysis of inflammatory cytokines in SS and NCWS patients.

    Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: C-X-C Motif Chemokine Ligand 13 (CXCL13)

    Measured: 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).

  29. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: lymphocyte T helper (Th)1

    Measured: 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).

  30. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: lymphocyte T helper Th17

    Measured: 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).

  31. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: lymphocyte T helper Th22

    Measured: 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).

  32. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: lymphocyte T regulator (Treg)

    Measured: 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).

  33. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: follicular B helper T cells (Tfh)

    Measured: 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).

  34. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: innate lymphocyte cell (ILC)1

    Measured: 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).

  35. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: innate lymphocyte cell (ILC)2

    Measured: 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).

  36. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: innate lymphocyte cell (ILC)3

    Measured: 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).

  37. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: lymphocyte T cluster of differentiation (CD)8+

    Measured: 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).

  38. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: natural killer (NK) T cells

    Measured: 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).

  39. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern: B cells

    Measured: 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).

  40. Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of SS.

    Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of SS pathogenetic pattern:interferon type I signature in cluster of differentiation (CD)14+ monocytes

    Measured: 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).

  41. Peripheral blood ELISA analysis of intestinal permeability markers in SS and NCWS patients.

    Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: zonulin

    Measured: 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).

  42. Peripheral blood ELISA analysis of intestinal permeability markers in SS and NCWS patients.

    Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: F-Actin

    Measured: 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).

  43. LA/MA test in SS and NCWS patients.

    Lactulose/Mannitol (LA/MA) test will be performed to assess in vivo intestinal permeability.

    Measured: 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).

  44. Fecal ELISA analysis of inflammatory gut marker in SS and NCWS patients.

    Fecal ELISA analysis of inflammatory gut marker will be performed to assess fecal calprotectin.

    Measured: 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).

  45. Gut microbiota assessment in SS and NCWS patients.

    Gut microbiota assessment will be performed by quantification of gut microbiota on stools samples.

    Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2022
  2. Study start1 Jan 2023
  3. Primary completion31 Dec 2025
  4. Study completion30 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, randomized, placebo-controlled, cross-over, single center clinical trials.
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05644795
Sponsor's protocol ID
ACPM31
Status last verified
Apr 2026
First submitted
9 Nov 2022
Last updated
5 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 28753927

  • 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.

    PubMed 24275240

  • 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.

    PubMed 22825366

  • 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.

    PubMed 33095148

  • 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.

    PubMed 32503132

  • 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.

    PubMed 31683641

Questions about this trial

What is this clinical trial studying?

A study testing Wheat/milk free diet (W/MFD) group and Rice/turkey free diet (R/TFD) group in people with Sjogren's Syndrome and Non-celiac Gluten Sensitivity, run by University of Palermo at 3 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Self-perceived non-celiac wheat sensitivity (NCWS) questionnaire in SS patients (time frame: Before enter the study). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05644795, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.

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