Non-celiac Wheat SensitivityNCT05469971
KIR Genes and Non-Celiac Wheat Sensitivity
An observational study of Non-celiac Wheat Sensitivity, run by University of Palermo at 4 sites in Italy.
Trial summary
Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extraintestinal symptoms which are triggered by gluten ingestion in the absence of celiac disease (CD) and wheat allergy. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Non-celiac Wheat Sensitivity
- What is being tested?
- KIR genotyping
- Type of treatment
- Injection or infusion
- How many people
- 170 participants
- Where
- 4 sitesItaly
- Study dates
- 1 Nov 2022to 30 Sep 2023
- Phase
- Observational
- 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
- Adult, Older adult
Study population: 50 NCWS patients, 50 CD patients, and 50 healthy blood donors.
- Inclusion Criteria for NCWS patients
- age >18 and <65 years
- subjects with gluten/wheat-dependent symptoms, both intestinal and extra-intestinal
- negativity of anti-deamidated gliadin protein (DGP) immunoglobulins (Ig) class A (IgA) and IgG, anti-tissue transglutaminase (tTG) IgA and IgG, Endomysium antibody (EMA)
- absence of villous atrophy at the duodenal level, documented in all patients with HLA DQ2 and/or DQ8 (therefore, regardless of the negativity of CD-specific serum antibodies), evaluated when patients had a minimum intake of 100 grams of pasta and/or bread a day, for at least 45 days
- absence of wheat allergy (negative prick-test and/or specific serum IgE assay for wheat, gluten and gliadin)
- resolution of symptoms with a strict standard elimination diet, i.e., "oligoantigenic" (without wheat, cow's milk, egg, tomato and chocolate, and other foods self-reported by the patient as causing symptoms), for at least 4 weeks, followed by the reappearance of the same after a Double-Blind Placebo-Controlled Challenge (DBPCC) with gluten/wheat
- complete medical records
- duration of follow-up greater than 12 months after initial diagnosis and at least 2 outpatient visits during the follow-up period.
- Exclusion Criteria for NCWS patients
- age <18 and >65 years
- alcohol and/or drug abuse
- self-exclusion of gluten/wheat from the diet and refusal to reintroduce it, for diagnostic purposes, before entering the study
- treatment with steroids and/or non-steroidal anti-inflammatory drugs (NSAIDs) in the 2 weeks prior to performing duodenal biopsies
- positivity of EMA in the culture medium of duodenal biopsies, even in the presence of a normal villus/crypt ratio in the duodenal mucosa
- incomplete medical records
- lack of clinical follow-up of at least 12 months from diagnosis
- pregnancy
- diagnosis of chronic inflammatory bowel disease or other organic pathology affecting the digestive system, diseases of the nervous system, major psychiatric disorders, infectious diseases, immunological deficits, and impairments that limit physical activity.
- Criteria for inclusion of patients with CD
- age >18 and <65 years
- subjects with gluten/wheat-dependent symptoms, both intestinal and extraintestinal, who meet the diagnostic criteria of CD reported in the current guidelines ("four out of five rule"): 1) typical intestinal and extraintestinal signs and symptoms of CD; 2) antibody positivity (both immunoglobulin (Ig) A class anti-tTG and EMA in IgA-sufficient or IgG class anti-tTG and EMA in IgA-deficient subjects); 3) HLA-DQ2 and/or -DQ8 positivity; 4) intestinal damage (demonstrated by histology on duodenal biopsies according to the Marsh classification); 5) clinical response to gluten-free diet (GFD) (e.g., resolution of intestinal and/or extra-intestinal symptoms).
- Exclusion criteria for patients with CD
- age <18 and >65 years
- alcohol and/or drug abuse
- incomplete medical records
- lack of clinical follow-up of at least 12 months from diagnosis
- pregnancy
- diagnosis of chronic inflammatory bowel disease or other organic pathology affecting the digestive system, diseases of the nervous system, major psychiatric disorders, infectious diseases, immunological deficits and impairments that limit physical activity.
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Internal Medicine Division of the "Cervello-Villa Sofia" Hospital
Palermo, PA, 90146
Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo
Palermo, 90127
Department of Internal Medicine, University Hospital of Palermo
Palermo, 90129
Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
Sciacca, Agrigento, 92019
About this study
Official title: Contribution of KIR Genes on the Genetic Predisposition to Non-Celiac Wheat Sensitivity
Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extraintestinal symptoms which are triggered by gluten ingestion in the absence of celiac disease (CD) and wheat allergy. In the last years studies suggested that wheat components other than gluten can be responsible of symptom's triggering, thus the term "non-celiac wheat sensitivity" (NCWS) has been proposed as a more appropriate label. To date, different pathogenetic mechanisms have been proposed, but no conclusive data have been reported; among these, some study groups a possible role of innate immunity and of Natural Killer (NK) cells. KIR (Killer Immunoglobulin-like Receptors) regulate the activation of NK cells through their interaction with Human Leucocyte Antigens (HLA). Both KIR and HLA loci are highly polymorphic, and, in the case of KIR, two main haplotypes have been identified: A and B. Haplotype A is the simplest and correlates mainly with NK inhibition, while haplotype B has a variable number of genes, most of which activate NK cells. The investigators hypothesis is that the genetic variants of KIR, which define the haplotype "inhibitor" or "activator", can affect the development and the course of NCWS too. Thus, the researchers aimed to:1. Identify putative KIR genetic variants in NCWS patients (50 subjects) respect to celiac disease patients (50 subjects) and blood donors (50 subjects); 2. Evaluate the possible association of KIR genetic variants with specific clinical manifestations of patients with NCWS.
Read the detailed description
Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extraintestinal symptoms which are triggered by gluten ingestion in the absence of celiac disease (CD) and wheat allergy. Despite the great interest in NCGS, much remains unknown about its pathogenesis. Some studies seem to suggest that wheat components other than gluten (i.e. amylase/trypsin inhibitors, ATIs) can be responsible of symptom's triggering, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed as a more appropriate label. NCWS pathogenesis has been attributed to very different mechanisms: innate or adaptive immunity, incomplete digestion and/or absorption of fermentable oligosaccharides and disaccharides, monosaccharides, and polyols, and, finally, psychological effect. Although NCWS might be considered in its clinical features like CD, to date, no data are available about genes that confer a higher genetic predisposition to the disease. It is known that, in contrast to CD, patients with NCWS do not have a characteristic Human Leucocyte Antigens (HLA) genotype/phenotype, even if HLA DQ2/DQ8 alleles are present in 40-50% of these patients, a value higher than that of the general population (30%). Many studies ascertained the importance of innate immunity and of Natural Killer (NK) cells in the pathogenesis of NCWS. KIRs (Killer Immunoglobulin-like Receptors) regulate the activation of NK cells through their interaction with HLA. Both KIR and HLA loci are highly polymorphic, and, in the case of KIR, two main haplotypes have been identified: A and B. Haplotype A is the simplest and correlates mainly with NK inhibition, while haplotype B has a variable number of genes, most of which activate NK cells. More in general, several studies have shown that haplotypes containing predominantly activator genes confer protection against viral infections and susceptibility to the development of autoimmune and neoplastic diseases. In the context of CD, NK cells are one of the main components of innate immunity and are involved in the destruction of epithelial cells and their cytotoxic activity is closely related to the function of KIRs. The investigators hypothesis is that the genetic variants of KIR, which define the haplotype "inhibitor" or "activator", can affect the development and the course of NCWS too. Thus, the researchers aimed to: 1. Identify putative KIR genetic variants in NCWS patients (50 subjects) respect to celiac disease patients (50 subjects) and blood donors (50 subjects); 2. Evaluate the possible association of KIR genetic variants with specific clinical manifestations of patients with NCWS.
- Conditions
- Non-celiac Wheat Sensitivity
- Being tested
- KIR genotyping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KIR genotypingGenetic
DNA extraction and KIR genotyping by KIR SSO Genotyping Test (One Lambda, Thermo Fisher, Monza, Italy).
| Study group | Role | What they receive |
|---|---|---|
| NCWS patients | The researchers will enrol NCWS, presenting with IBS and/or dyspepsia-like symptoms, according to the Rome IV criteria (20). These patients were diagnosed by DBPC wheat challenge between January 2010 and June 2022 in three tertiary centers for "gluten-related disorders" (Department of Internal Medicine, University Hospital of Palermo, Italy; Department of Internal Medicine, "Cervello" Hospital of Palermo, Italy, and Department of Internal Medicine, Hospital of Sciacca, Agrigento, Italy. Receives: Genetic: KIR genotyping | |
| Celiac disease | The researchers will enrol CD patients diagnosed between January 2010 and June 2022 in three tertiary centers for "gluten-related disorders" (Department of Internal Medicine, University Hospital of Palermo, Italy; Department of Internal Medicine, "Cervello" Hospital of Palermo, Italy, and Department of Internal Medicine, Hospital of Sciacca, Agrigento, Italy. Receives: Genetic: KIR genotyping | |
| Blood donors | The researchers will enroll blood donors from the Transfusion Centre of the University Hospital of Palermo, Italy. Receives: Genetic: KIR genotyping |
What is being measured
The primary outcome is the main question the study is designed to answer.
KIR genetic variants in NCWS patients respect to CD patients and blood donors
Evaluation of the presence and prevalence of KIR genetic variants (haplotype A or B) in NCWS patients respect to CD patients and blood donors.
Measured: Through study completion, an average of 1 year
Association between KIR genetic variants and clinical manifestation of NCWS patients
Association between KIR genetic variants and the clinical symptoms (irritable bowel syndrome-like, functional dyspepsia-like, and extraintestinal) of NCWS patients.
Measured: Through study completion, an average of 1 year
Association between KIR genetic variants and associated autoimmune diseases of NCWS patients
Association between KIR genetic variants and the associated autoimmune diseases (e.g., autoimmune thyroiditis) of NCWS patients.
Measured: Through study completion, an average of 1 year
Association between KIR genetic variants and coexistent other food allergies/intolerances of NCWS patients
Association between KIR genetic variants and the coexistent other food allergies/intolerances (e.g., self-reported milk intolerance) of NCWS patients.
Measured: Through study completion, an average of 1 year
Association between KIR genetic variants and HLA DQ2-DQ8 genotypes of NCWS patients.
Association between KIR genetic variants and the HLA DQ2-DQ8 genotypes of NCWS patients.
Measured: Through study completion, an average of 1 year
Association between KIR genetic variants and duodenal histology of NCWS patients.
Association between KIR genetic variants and the duodenal histology (i.e., Marsh-Oberuber classification) of NCWS patients.
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2022
- Study start1 Nov 2022
- Primary completion30 Jun 2023
- Study completion30 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Non-celiac Wheat SensitivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Palermo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pasquale Mansueto, University of Palermo
- Investigators
- Antonio Carroccio, MD, Study chair, Department of Internal Medicine, "Cervello" Hospital of Palermo, ItalyMarcello Ciaccio, MD, Study director, Institute of Clinical Biochemistry, University of Palermo, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05469971
- Sponsor's protocol ID
- ACPM29
- Status last verified
- Nov 2023
- First submitted
- 11 Jul 2022
- Last updated
- 28 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Carroccio A, Soresi M, Chiavetta M, La Blasca F, Compagnoni S, Giuliano A, Fayer F, Mandreucci F, Castellucci D, Seidita A, Affronti A, Florena AM, Mansueto P. Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity. Nutrients. 2021 Jun 8;13(6):1971. doi: 10.3390/nu13061971.
PubMed 34201313Mansueto 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.
PubMed 32658621Mansueto 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.
PubMed 24533607Carroccio 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 22825366Santin I, Castellanos-Rubio A, Perez de Nanclares G, Vitoria JC, Castano L, Bilbao JR. Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4. Genes Immun. 2007 Mar;8(2):171-6. doi: 10.1038/sj.gene.6364367. Epub 2007 Jan 11.
PubMed 17215859Fernandez-Jimenez N, Santin I, Irastorza I, Plaza-Izurieta L, Castellanos-Rubio A, Vitoria JC, Bilbao JR. Upregulation of KIR3DL1 gene expression in intestinal mucosa in active celiac disease. Hum Immunol. 2011 Aug;72(8):617-20. doi: 10.1016/j.humimm.2011.04.008. Epub 2011 May 13.
PubMed 21616111Caggiari L, Toffoli G, De Re V, Orzes N, Spina M, De Zorzi M, Maiero S, Cannizzaro R, Canzonieri V. KIR/HLA combination associated with the risk of complications in celiac disease. Int J Biol Markers. 2011 Oct-Dec;26(4):221-8. doi: 10.5301/JBM.2011.8903.
PubMed 22180175Akar HH, Patiroglu T, Sevinc E, Aslan D, Okdemir D, Kurtoglu S. Contribution of KIR genes, HLA class I ligands, and KIR/HLA class I ligand combinations on the genetic predisposition to celiac disease and coexisting celiac disease and type 1 diabetes mellitus. Rev Esp Enferm Dig. 2015 Sep;107(9):547-53. doi: 10.17235/reed.2015.3817/2015.
PubMed 26334461
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contribution of KIR Genes on the Genetic Predisposition to Non-Celiac Wheat Sensitivity
- ClinicalTrials.gov ID
- NCT05469971
- Acronym / sponsor ID
- ACPM29
- Conditions
- Non-celiac Wheat Sensitivity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- University of PalermoUniversity, hospital or other
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 22 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extraintestinal symptoms which are triggered by gluten ingestion in the absence of celiac disease (CD) and wheat allergy. In the last years studies suggested that wheat components other than gluten can be responsible of symptom's triggering, thus the term "non-celiac wheat sensitivity" (NCWS) has been proposed as a more appropriate label. To date, different pathogenetic mechanisms have been proposed, but no conclusive data have been reported; among these, some study groups a possible role of innate immunity and of Natural Killer (NK) cells. KIR (Killer Immunoglobulin-like Receptors) regulate the activation of NK cells through their interaction with Human Leucocyte Antigens (HLA). Both KIR and HLA loci are highly polymorphic, and, in the case of KIR, two main haplotypes have been identified: A and B. Haplotype A is the simplest and correlates mainly with NK inhibition, while haplotype B has a variable number of genes, most of which activate NK cells. The investigators hypothesis is that the genetic variants of KIR, which define the haplotype "inhibitor" or "activator", can affect the development and the course of NCWS too. Thus, the researchers aimed to:1. Identify putative KIR genetic variants in NCWS patients (50 subjects) respect to celiac disease patients (50 subjects) and blood donors (50 subjects); 2. Evaluate the possible association of KIR genetic variants with specific clinical manifestations of patients with NCWS.
Detailed description
Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extraintestinal symptoms which are triggered by gluten ingestion in the absence of celiac disease (CD) and wheat allergy. Despite the great interest in NCGS, much remains unknown about its pathogenesis. Some studies seem to suggest that wheat components other than gluten (i.e. amylase/trypsin inhibitors, ATIs) can be responsible of symptom's triggering, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed as a more appropriate label. NCWS pathogenesis has been attributed to very different mechanisms: innate or adaptive immunity, incomplete digestion and/or absorption of fermentable oligosaccharides and disaccharides, monosaccharides, and polyols, and, finally, psychological effect. Although NCWS might be considered in its clinical features like CD, to date, no data are available about genes that confer a higher genetic predisposition to the disease. It is known that, in contrast to CD, patients with NCWS do not have a characteristic Human Leucocyte Antigens (HLA) genotype/phenotype, even if HLA DQ2/DQ8 alleles are present in 40-50% of these patients, a value higher than that of the general population (30%). Many studies ascertained the importance of innate immunity and of Natural Killer (NK) cells in the pathogenesis of NCWS. KIRs (Killer Immunoglobulin-like Receptors) regulate the activation of NK cells through their interaction with HLA. Both KIR and HLA loci are highly polymorphic, and, in the case of KIR, two main haplotypes have been identified: A and B. Haplotype A is the simplest and correlates mainly with NK inhibition, while haplotype B has a variable number of genes, most of which activate NK cells. More in general, several studies have shown that haplotypes containing predominantly activator genes confer protection against viral infections and susceptibility to the development of autoimmune and neoplastic diseases. In the context of CD, NK cells are one of the main components of innate immunity and are involved in the destruction of epithelial cells and their cytotoxic activity is closely related to the function of KIRs. The investigators hypothesis is that the genetic variants of KIR, which define the haplotype "inhibitor" or "activator", can affect the development and the course of NCWS too. Thus, the researchers aimed to: 1. Identify putative KIR genetic variants in NCWS patients (50 subjects) respect to celiac disease patients (50 subjects) and blood donors (50 subjects); 2. Evaluate the possible association of KIR genetic variants with specific clinical manifestations of patients with NCWS.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NCWS patients | – | Genetic: KIR genotypingThe researchers will enrol NCWS, presenting with IBS and/or dyspepsia-like symptoms, according to the Rome IV criteria (20). These patients were diagnosed by DBPC wheat challenge between January 2010 and June 2022 in three tertiary centers for "gluten-related disorders" (Department of Internal Medicine, University Hospital of Palermo, Italy; Department of Internal Medicine, "Cervello" Hospital of Palermo, Italy, and Department of Internal Medicine, Hospital of Sciacca, Agrigento, Italy. |
| Celiac disease | – | Genetic: KIR genotypingThe researchers will enrol CD patients diagnosed between January 2010 and June 2022 in three tertiary centers for "gluten-related disorders" (Department of Internal Medicine, University Hospital of Palermo, Italy; Department of Internal Medicine, "Cervello" Hospital of Palermo, Italy, and Department of Internal Medicine, Hospital of Sciacca, Agrigento, Italy. |
| Blood donors | – | Genetic: KIR genotypingThe researchers will enroll blood donors from the Transfusion Centre of the University Hospital of Palermo, Italy. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- 50 NCWS patients, 50 CD patients, and 50 healthy blood donors.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KIR genotypingDNA extraction and KIR genotyping by KIR SSO Genotyping Test (One Lambda, Thermo Fisher, Monza, Italy). | Genetic | Blood donors, Celiac disease, NCWS patients |
Primary outcome
KIR genetic variants in NCWS patients respect to CD patients and blood donors
Time frame: Through study completion, an average of 1 year
Evaluation of the presence and prevalence of KIR genetic variants (haplotype A or B) in NCWS patients respect to CD patients and blood donors.
Association between KIR genetic variants and clinical manifestation of NCWS patients
Time frame: Through study completion, an average of 1 year
Association between KIR genetic variants and the clinical symptoms (irritable bowel syndrome-like, functional dyspepsia-like, and extraintestinal) of NCWS patients.
Association between KIR genetic variants and associated autoimmune diseases of NCWS patients
Time frame: Through study completion, an average of 1 year
Association between KIR genetic variants and the associated autoimmune diseases (e.g., autoimmune thyroiditis) of NCWS patients.
Association between KIR genetic variants and coexistent other food allergies/intolerances of NCWS patients
Time frame: Through study completion, an average of 1 year
Association between KIR genetic variants and the coexistent other food allergies/intolerances (e.g., self-reported milk intolerance) of NCWS patients.
Association between KIR genetic variants and HLA DQ2-DQ8 genotypes of NCWS patients.
Time frame: Through study completion, an average of 1 year
Association between KIR genetic variants and the HLA DQ2-DQ8 genotypes of NCWS patients.
Association between KIR genetic variants and duodenal histology of NCWS patients.
Time frame: Through study completion, an average of 1 year
Association between KIR genetic variants and the duodenal histology (i.e., Marsh-Oberuber classification) of NCWS patients.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
- Results publication: PubMed 34201313Carroccio A, Soresi M, Chiavetta M, La Blasca F, Compagnoni S, Giuliano A, Fayer F, Mandreucci F, Castellucci D, Seidita A, Affronti A, Florena AM, Mansueto P. Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity. Nutrients. 2021 Jun 8;13(6):1971. doi: 10.3390/nu13061971.
- Results publication: PubMed 32658621Mansueto 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.
- Results publication: PubMed 24533607Mansueto 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.
- Results publication: PubMed 22825366Carroccio 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.
- Results publication: PubMed 17215859Santin I, Castellanos-Rubio A, Perez de Nanclares G, Vitoria JC, Castano L, Bilbao JR. Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4. Genes Immun. 2007 Mar;8(2):171-6. doi: 10.1038/sj.gene.6364367. Epub 2007 Jan 11.
- Results publication: PubMed 21616111Fernandez-Jimenez N, Santin I, Irastorza I, Plaza-Izurieta L, Castellanos-Rubio A, Vitoria JC, Bilbao JR. Upregulation of KIR3DL1 gene expression in intestinal mucosa in active celiac disease. Hum Immunol. 2011 Aug;72(8):617-20. doi: 10.1016/j.humimm.2011.04.008. Epub 2011 May 13.
- Results publication: PubMed 22180175Caggiari L, Toffoli G, De Re V, Orzes N, Spina M, De Zorzi M, Maiero S, Cannizzaro R, Canzonieri V. KIR/HLA combination associated with the risk of complications in celiac disease. Int J Biol Markers. 2011 Oct-Dec;26(4):221-8. doi: 10.5301/JBM.2011.8903.
- Results publication: PubMed 26334461Akar HH, Patiroglu T, Sevinc E, Aslan D, Okdemir D, Kurtoglu S. Contribution of KIR genes, HLA class I ligands, and KIR/HLA class I ligand combinations on the genetic predisposition to celiac disease and coexisting celiac disease and type 1 diabetes mellitus. Rev Esp Enferm Dig. 2015 Sep;107(9):547-53. doi: 10.17235/reed.2015.3817/2015.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Carroccio, MD study chair
Department of Internal Medicine, "Cervello" Hospital of Palermo, Italy
Marcello Ciaccio, MD study director
Institute of Clinical Biochemistry, University of Palermo, Italy
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-celiac Wheat Sensitivity, run by University of Palermo at 4 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?
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 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. 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?
KIR genetic variants in NCWS patients respect to CD patients and blood donors (time frame: Through study completion, an average of 1 year). The study lists 6 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 NCT05469971, which also lists 8 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 28 Nov 2023; AzTrials last refreshed its copy on 30 Oct 2026.