Non-Celiac Wheat SensitivityNCT02823522
Non-Celiac Wheat Sensitivity: Permanent or Transient Condition?
An observational study of Non-Celiac Wheat Sensitivity, run by University of Palermo at 2 sites in Italy.
Trial summary
Non-Celiac Gluten Sensitivity (NCGS) has been recently included among the gluten-related diseases. Patients suffering from NCGS are diagnosed after carefully excluding celiac disease (CD), and immunoglobulin E (IgE)-mediated 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?
- Patients recruitment
- How many people
- 280 participants
- Where
- 2 sitesItaly
- Study dates
- Jul 2016to Dec 2025
- 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
- No healthy volunteers
- Adult, Older adult
Study population: The patients included in the previous retrospective study were contacted by phone, mail and e-mail and invited to come back to the respective clinics where they had been initially diagnosed as NCWS patients: the Department of Internal Medicine of the University Hospital of Palermo and the Department of Internal Medicine of the Hospital of Sciacca.
Who may be able to join
- Patients previously diagnosed with NCWS by DBPC challenge.
Who cannot join
- The 22 patients, included in the previous study, who tested positives for anti-endomysial antibodies (EmA) in the culture medium of the duodenal biopsies, even if the villi/crypts ratio in the duodenal mucosa was normal, were excluded from the present study.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Department of Internal Medicine, University Hospital of Palermo
Palermo, Palermo, 90129
Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
Sciacca, Agrigento, 92019
About this study
Official title: Non-Celiac Wheat Sensitivity: Permanent or Transient Condition? A Follow-up Study
Non-Celiac Gluten Sensitivity (NCGS) has been recently included among the gluten-related diseases. Patients suffering from NCGS are diagnosed after carefully excluding celiac disease (CD), and immunoglobulin E (IgE)-mediated wheat allergy. Then, in the absence of sensitive and specific diagnostic biomarkers for NCGS, a monitoring of the patient during elimination and re-introduction of wheat by a double-blind placebo controlled (DBPC) challenge method has been suggested as diagnostic hallmark. Some studies seem to suggest that wheat components other than gluten can cause the symptoms, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed instead of NCGS. While it is well known that CD is a long-life condition and a strict adherence to the gluten-free diet must be maintained, it is unknown whether this is valid for NCWS. On the year 2012, the researchers published a retrospective study, including 276 patients with irritable bowel syndrome (IBS)-like symptoms who had been diagnosed with NCWS using a DBPC challenge during a ten-years period (2001-2011). The present prospective study aimed to evaluate: A) how many of these patients are still following a wheat-free diet, and B) which percentage was still suffering from NCWS, diagnosed by DBPC wheat challenge, in a subgroup of that cohort.
Read the detailed description
Non-Celiac Gluten Sensitivity (NCGS) has been recently included among the gluten-related diseases. Patients suffering from NCGS are diagnosed after carefully excluding celiac disease (CD) diagnosis by negative CD-specific serum antibodies and absence of intestinal villi atrophy, and excluding IgE-mediated wheat allergy, by negative serum specific IgE and/or skin prick test with wheat antigens. Then, in the absence of sensitive and specific diagnostic biomarkers for NCGS, a monitoring of the patient during elimination and re-introduction of wheat by a double-blind placebo controlled (DBPC) challenge method has been suggested as diagnostic hallmark. Obviously, this a cumbersome and time-consuming procedure which has been used in few studies.
Despite an increasing percentage of the general population define themselves as "gluten-sensitive", and by the year 2017 the market of the gluten-free products will be worth 6.6 billion of dollars, doubts persist about many aspects of NCGS. Some studies seem to suggest that wheat components other than gluten can cause the symptoms, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed instead of NCGS. Furthermore, while it is well known that CD is a long-life condition and a strict adherence to the gluten-free diet must be maintained, it is unknown whether this is valid for NCWS.
On the year 2012, the researchers published a retrospective study, including 276 patients with irritable bowel syndrome (IBS)-like symptoms who had been diagnosed with NCWS using a DBPC challenge during a ten-years period (2001-2011).
The present prospective study aimed to evaluate the persistence of the NCWS condition in that cohort and, consequently, the researchers estimated : A) how many of these patients are still following a wheat-free diet, and B) which percentage was still suffering from NCWS, diagnosed by DBPC wheat challenge, in a subgroup of that cohort.
- Conditions
- Non-Celiac Wheat Sensitivity
- Being tested
- Patients recruitment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patients recruitmentOther
Between July and November 2016, the patients included in the previous retrospective study were contacted by phone, mail and e-mail and invited to come back to the respective clinics where they had been initially diagnosed as NCWS patients: the Department of Internal Medicine of the University Hospital of Palermo and the Department of Internal Medicine of the Hospital of Sciacca (province of Agrigento).
What is being measured
The primary outcome is the main question the study is designed to answer.
How many patients were still following a gluten-free or a wheat-free diet
A structured questionnaire was administered to evaluate how many patients were still following a gluten-free diet (GFD) and how many a wheat-free diet.
Measured: Between July and November 2016
Secondary outcomes (3)
Evaluation of the effect of the GFD on IBS symptoms
The researchers administered a modified version of the IBS Global Assessment of Improvement (IBS-GAI) score. A responder was defined as a patient whose symptoms were either 'moderately improved' or 'substantially improved' compared with the period preceding the NCWS diagnosis.
Measured: Between July and November 2016
Evaluation of the severity of the IBS condition
The researchers administered the IBS Symptom Severity Scale (IBS-SSS), evaluating the change in total IBS-SSS score from the first evaluation (time of the NCWS diagnosis) and the follow-up evaluation (present study). A respondent was classified as a patient whose overall symptom severity on the IBS-SSS changed >50 points.
Measured: Between July and November 2016
Re-evaluation of the NCWS condition by DBPC-Wheat challenge
Finally, the repetition of the DBPC-wheat challenge will be proposed to the patients still on GFD. Those who will accept will be randomized to undergo the challenge. It will be performed with the same method used in the retrospective study.
Measured: Between July and November 2016
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2016 (estimated)
- Study startJul 2016
- Primary completionAug 2024
- Study completionDec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 280 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, Principal investigator, Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02823522
- Sponsor's protocol ID
- ACPM11
- Status last verified
- Apr 2026
- First submitted
- 27 Jun 2016
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, Fasano A. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012 Feb 7;10:13. doi: 10.1186/1741-7015-10-13.
PubMed 22313950Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C. The Oslo definitions for coeliac disease and related terms. Gut. 2013 Jan;62(1):43-52. doi: 10.1136/gutjnl-2011-301346. Epub 2012 Feb 16.
PubMed 22345659Catassi C, Elli L, Bonaz B, Bouma G, Carroccio A, Castillejo G, Cellier C, Cristofori F, de Magistris L, Dolinsek J, Dieterich W, Francavilla R, Hadjivassiliou M, Holtmeier W, Korner U, Leffler DA, Lundin KE, Mazzarella G, Mulder CJ, Pellegrini N, Rostami K, Sanders D, Skodje GI, Schuppan D, Ullrich R, Volta U, Williams M, Zevallos VF, Zopf Y, Fasano A. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria. Nutrients. 2015 Jun 18;7(6):4966-77. doi: 10.3390/nu7064966.
PubMed 26096570Spence D. Bad medicine: food intolerance. BMJ. 2013 Jan 30;346:f529. doi: 10.1136/bmj.f529. No abstract available.
PubMed 23364064Carroccio 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 24275240Fasano A, Sapone A, Zevallos V, Schuppan D. Nonceliac gluten sensitivity. Gastroenterology. 2015 May;148(6):1195-204. doi: 10.1053/j.gastro.2014.12.049. Epub 2015 Jan 9.
PubMed 25583468Carroccio 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 22825366Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997 Apr;11(2):395-402. doi: 10.1046/j.1365-2036.1997.142318000.x.
PubMed 9146781Carroccio A, D'Alcamo A, Iacono G, Soresi M, Iacobucci R, Arini A, Geraci G, Fayer F, Cavataio F, La Blasca F, Florena AM, Mansueto P. Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up. Gastroenterology. 2017 Jul;153(1):56-58.e3. doi: 10.1053/j.gastro.2017.03.034. Epub 2017 Mar 30.
PubMed 28365444
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Celiac Wheat Sensitivity: Permanent or Transient Condition? A Follow-up Study
- ClinicalTrials.gov ID
- NCT02823522
- Acronym / sponsor ID
- ACPM11
- Conditions
- Non-Celiac Wheat Sensitivity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- University of PalermoUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- Aug 2024 (actual)
- Study completion
- Dec 2025 (actual)
- First posted
- 6 Jul 2016 (estimated)
- 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) has been recently included among the gluten-related diseases. Patients suffering from NCGS are diagnosed after carefully excluding celiac disease (CD), and immunoglobulin E (IgE)-mediated wheat allergy. Then, in the absence of sensitive and specific diagnostic biomarkers for NCGS, a monitoring of the patient during elimination and re-introduction of wheat by a double-blind placebo controlled (DBPC) challenge method has been suggested as diagnostic hallmark. Some studies seem to suggest that wheat components other than gluten can cause the symptoms, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed instead of NCGS. While it is well known that CD is a long-life condition and a strict adherence to the gluten-free diet must be maintained, it is unknown whether this is valid for NCWS. On the year 2012, the researchers published a retrospective study, including 276 patients with irritable bowel syndrome (IBS)-like symptoms who had been diagnosed with NCWS using a DBPC challenge during a ten-years period (2001-2011). The present prospective study aimed to evaluate: A) how many of these patients are still following a wheat-free diet, and B) which percentage was still suffering from NCWS, diagnosed by DBPC wheat challenge, in a subgroup of that cohort.
Detailed description
Non-Celiac Gluten Sensitivity (NCGS) has been recently included among the gluten-related diseases. Patients suffering from NCGS are diagnosed after carefully excluding celiac disease (CD) diagnosis by negative CD-specific serum antibodies and absence of intestinal villi atrophy, and excluding IgE-mediated wheat allergy, by negative serum specific IgE and/or skin prick test with wheat antigens. Then, in the absence of sensitive and specific diagnostic biomarkers for NCGS, a monitoring of the patient during elimination and re-introduction of wheat by a double-blind placebo controlled (DBPC) challenge method has been suggested as diagnostic hallmark. Obviously, this a cumbersome and time-consuming procedure which has been used in few studies.
Despite an increasing percentage of the general population define themselves as "gluten-sensitive", and by the year 2017 the market of the gluten-free products will be worth 6.6 billion of dollars, doubts persist about many aspects of NCGS. Some studies seem to suggest that wheat components other than gluten can cause the symptoms, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed instead of NCGS. Furthermore, while it is well known that CD is a long-life condition and a strict adherence to the gluten-free diet must be maintained, it is unknown whether this is valid for NCWS.
On the year 2012, the researchers published a retrospective study, including 276 patients with irritable bowel syndrome (IBS)-like symptoms who had been diagnosed with NCWS using a DBPC challenge during a ten-years period (2001-2011).
The present prospective study aimed to evaluate the persistence of the NCWS condition in that cohort and, consequently, the researchers estimated : A) how many of these patients are still following a wheat-free diet, and B) which percentage was still suffering from NCWS, diagnosed by DBPC wheat challenge, in a subgroup of that cohort.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The patients included in the previous retrospective study were contacted by phone, mail and e-mail and invited to come back to the respective clinics where they had been initially diagnosed as NCWS patients: the Department of Internal Medicine of the University Hospital of Palermo and the Department of Internal Medicine of the Hospital of Sciacca.
Key inclusion criteria (1 listed)
- Patients previously diagnosed with NCWS by DBPC challenge.
Key exclusion criteria (1 listed)
- The 22 patients, included in the previous study, who tested positives for anti-endomysial antibodies (EmA) in the culture medium of the duodenal biopsies, even if the villi/crypts ratio in the duodenal mucosa was normal, were excluded from the present study.
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 |
|---|---|---|
| Patients recruitmentBetween July and November 2016, the patients included in the previous retrospective study were contacted by phone, mail and e-mail and invited to come back to the respective clinics where they had been initially diagnosed as NCWS patients: the Department of Internal Medicine of the University Hospital of Palermo and the Department of Internal Medicine of the Hospital of Sciacca (province of Agrigento). | Other | – |
Primary outcome
How many patients were still following a gluten-free or a wheat-free diet
Time frame: Between July and November 2016
A structured questionnaire was administered to evaluate how many patients were still following a gluten-free diet (GFD) and how many a wheat-free diet.
3 secondary outcomes
Evaluation of the effect of the GFD on IBS symptoms
Time frame: Between July and November 2016
Evaluation of the severity of the IBS condition
Time frame: Between July and November 2016
Re-evaluation of the NCWS condition by DBPC-Wheat challenge
Time frame: Between July and November 2016
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 5 May 2026.
- Results publication: PubMed 22313950Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, Fasano A. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012 Feb 7;10:13. doi: 10.1186/1741-7015-10-13.
- Results publication: PubMed 22345659Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C. The Oslo definitions for coeliac disease and related terms. Gut. 2013 Jan;62(1):43-52. doi: 10.1136/gutjnl-2011-301346. Epub 2012 Feb 16.
- Results publication: PubMed 26096570Catassi C, Elli L, Bonaz B, Bouma G, Carroccio A, Castillejo G, Cellier C, Cristofori F, de Magistris L, Dolinsek J, Dieterich W, Francavilla R, Hadjivassiliou M, Holtmeier W, Korner U, Leffler DA, Lundin KE, Mazzarella G, Mulder CJ, Pellegrini N, Rostami K, Sanders D, Skodje GI, Schuppan D, Ullrich R, Volta U, Williams M, Zevallos VF, Zopf Y, Fasano A. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria. Nutrients. 2015 Jun 18;7(6):4966-77. doi: 10.3390/nu7064966.
- Results publication: PubMed 23364064Spence D. Bad medicine: food intolerance. BMJ. 2013 Jan 30;346:f529. doi: 10.1136/bmj.f529. No abstract available.
- Results publication: PubMed 24275240Carroccio 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.
- Results publication: PubMed 25583468Fasano A, Sapone A, Zevallos V, Schuppan D. Nonceliac gluten sensitivity. Gastroenterology. 2015 May;148(6):1195-204. doi: 10.1053/j.gastro.2014.12.049. Epub 2015 Jan 9.
- 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 9146781Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997 Apr;11(2):395-402. doi: 10.1046/j.1365-2036.1997.142318000.x.
- Derived from this study: PubMed 28365444Carroccio A, D'Alcamo A, Iacono G, Soresi M, Iacobucci R, Arini A, Geraci G, Fayer F, Cavataio F, La Blasca F, Florena AM, Mansueto P. Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up. Gastroenterology. 2017 Jul;153(1):56-58.e3. doi: 10.1053/j.gastro.2017.03.034. Epub 2017 Mar 30.
- 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 principal investigator
Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
2 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 2 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 1 inclusion and 1 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 2 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?
How many patients were still following a gluten-free or a wheat-free diet (time frame: Between July and November 2016). 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 NCT02823522, which also lists 9 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; AzTrials last refreshed its copy on 28 Oct 2026.