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Response to Different Wheat Genotypes in Not-celiac Wheat Sensitivity

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ClinicalTrials.gov Identifier: NCT03024775
Recruitment Status : Recruiting
First Posted : January 19, 2017
Last Update Posted : September 5, 2018
Sponsor:
Information provided by (Responsible Party):
Pasquale Mansueto, University of Palermo

Tracking Information
First Submitted Date  ICMJE December 30, 2016
First Posted Date  ICMJE January 19, 2017
Last Update Posted Date September 5, 2018
Actual Study Start Date  ICMJE January 2017
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2017)
  • Inflammatory response to wheat genotypes by PBMC of NCWS patients and healthy control subjects. [ Time Frame: Through study completion, an average of 6 months ]
    Cytokines evaluation in response to gluten and non-gluten proteins from total kernel proteins of different wheat genotypes (i.e. ancient vs. modern vs. genetically modified) by PBMC of patients with a definitive diagnosis of NCWS, at the end of the diagnostic Double-Blind Placebo-Controlled (DBPC) wheat challenge, and of healthy control subjects.
  • Inflammatory response to wheat genotypes by rectal immunocytes of NCWS patients and healthy control subjects. [ Time Frame: Through study completion, an average of 6 months ]
    Rectal immunocytes evaluation in response to gluten and non-gluten proteins from total kernel proteins of different wheat genotypes (i.e. ancient vs. modern vs. genetically modified) by immunocytes extracted by the rectal mucosa of patients with a definitive diagnosis of NCWS, at the end of the diagnostic Double-Blind Placebo-Controlled (DBPC) wheat challenge, and of healthy control subjects.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03024775 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2017)
Clinical response to wheat genotypes in NCWS patients [ Time Frame: Change from baseline at 2 weeks ]
Symptoms evaluation before and after a 2 weeks challenge with two wheat genotypes showing the highest and the lowest in vitro inflammatory response in diagnosed NCWS patients on gluten-free diet. During the challenge periods, the severity of symptoms will be recorded: the patients will complete a 100mm visual analog scale, which assesses the specific symptoms they report. The challenges will be considered positive if the same symptoms which had been initially present will reappear after their disappearance on elimination diet.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Response to Different Wheat Genotypes in Not-celiac Wheat Sensitivity
Official Title  ICMJE Clinical Response and Cytokines Production After Challenge With Different Wheat Genotypes in Patients With Not-celiac Wheat Sensitivity.
Brief Summary Non-celiac gluten sensitivity (NCGS) is a condition where intestinal and extraintestinal symptoms are triggered by gluten ingestion in the absence of celiac disease and wheat allergy. Despite the great interest in NCGS, much remains unknown about the pathogenesis. Some studies seem to suggest that wheat components other than gluten (i.e. amylase/trypsine inhibitors, ATIs) can cause the symptoms, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed instead of NCGS. It is believed that this condition is worldwide increasing, due to the evolution of wheat breeding (i.e. consumption of wheats with high gluten content), and that ancient wheats are better tolerated by NCWS patients than the modern ones. Therefore, the aim of the study is to determine whether the common belief regarding the fact that ancient wheats are better tolerated by NCWS patients than the modern ones is confirmed by scientific data, and to identify the wheat kernel components triggering this pathology. The availability of wheat materials with opposite characteristics, such as the period of development (ancient vs. modern), or the technological properties (cultivars with weak glutens vs. strong gluten), or the presence/absence of specific ATIs polypeptides, will allow to define the role played by these factors. Therefore, the study has two objectives: 1) extraction and testing of total kernel proteins, in order to evaluate the inflammatory response to gluten and non-gluten proteins by peripheral blood mononuclear cells (PBMC) and immunocytes extracted by the rectal mucosa of NCWS patients and healthy control subjects, and 2) clinically testing two wheat genotypes, selected on the basis of the previous in vitro studies, showing the highest and the lowest in vitro inflammatory response, in order to verify their effect in triggering NCWS symptoms.
Detailed Description Non-celiac gluten sensitivity (NCGS) is a condition where intestinal and extraintestinal symptoms are triggered by gluten ingestion in the absence of celiac disease and wheat allergy. Despite the great interest in NCGS, much remains unknown about the pathogenesis. Some studies seem to suggest that wheat components other than gluten (i.e. amylase/trypsine inhibitors, ATIs) can cause the symptoms, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed instead of NCGS. 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. In addition, it is believed that this condition is worldwide increasing, due to the evolution of wheat breeding (i.e. consumption of wheats with high gluten content), and that ancient wheats are better tolerated by NCWS patients than the modern ones. Therefore, the aim of the study is to determine whether the common belief regarding the fact that ancient wheats are better tolerated by NCWS patients than the modern ones is confirmed by scientific data, and to identify the wheat kernel components triggering this pathology. The availability of wheat materials with opposite characteristics, such as the period of development (ancient vs. modern), or the technological properties (cultivars with weak glutens vs. strong gluten), or the presence/absence of specific ATIs polypeptides, will allow to define the role played by these factors. The researchers take into consideration different tetraploid wheat genotypes derived from the Italian breeding activity carried out during the 20th century in comparison with landraces, primitive and old wheat cultivars previously cultivated and used mostly in Southern Italy for pasta and bread production, together with an experimental genetically modified (GM) wheat line expressing a lower amount of ATIs. For the purpose of the study, the collection has been subdivided into 5 groups, according to the breeding period. Wheat genotypes will be also evaluated for several parameters: protein content, gluten index, quantitative analysis of ATIs proteins by Mass Spectrometry, etc. The project has two objectives, related to the influence of wheat consumption on health: 1) extraction and testing of total kernel proteins, in order to evaluate the inflammatory response to gluten and non-gluten proteins by peripheral blood mononuclear cells (PBMC) and immunocytes extracted by the rectal mucosa of NCWS patients and healthy control subjects, and 2) clinically testing two wheat genotypes, selected on the basis of the previous in vitro studies, showing the highest and the lowest in vitro inflammatory response, in order to verify their effect in triggering NCWS symptoms.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Non-celiac Wheat Sensitivity
Intervention  ICMJE
  • Dietary Supplement: Wheat flour
    Wheat flour will be administered three times per day for 15 days.
  • Dietary Supplement: Placebo
    Placebo (xylose) will be administered three times per day for 15 days.
Study Arms  ICMJE
  • Active Comparator: Active Comparator 1
    Wheat flour with high inflammatory response will be administered blindly versus placebo for 15 days in NCWS patients.
    Intervention: Dietary Supplement: Wheat flour
  • Active Comparator: Active Comparator 2
    Wheat flour with low inflammatory response will be administered blindly versus placebo for 15 days in NCWS patients.
    Intervention: Dietary Supplement: Wheat flour
  • Placebo Comparator: Placebo 1
    Placebo (xylose) will be administered blindly versus wheat flour with high inflammatory response for 15 days in NCWS patients.
    Intervention: Dietary Supplement: Placebo
  • Placebo Comparator: Placebo 2
    Placebo (xylose) will be administered blindly versus wheat flour with low inflammatory response for 15 days in NCWS patients.
    Intervention: Dietary Supplement: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 16, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2019
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

All the patients will meet the recently proposed criteria:

  • negative serum anti-tissue transglutaminase and antiendomysium (EmA) immunoglobulin (Ig)A and IgG antibodies
  • absence of intestinal villous atrophy
  • IgE-mediated immunoallergic tests negative to wheat (skin prick tests and/or serum specific IgE detection)
  • follow-up duration >12 months after the initial diagnosis
  • at least two outpatient visits during the follow-up period.

Adjunctive criteria adopted in our patients will be:

  • resolution of the gastrointestinal symptoms on a standard elimination diet, without wheat, cow's milk, egg, tomato, chocolate, or other food(s) causing self-reported symptoms
  • symptom reappearance on DBPC wheat challenge, performed as described previously. As in previous studies, DBPC cow's milk protein challenge and other "open" food challenges will be also performed.

Exclusion Criteria:

Exclusion criteria will be:

  • age <18 years
  • positive EmA in the culture medium of the duodenal biopsies, even if the villi to crypts ratio in the duodenal mucosa was normal
  • self-exclusion of wheat from the diet and refusal to reintroduce it before entering the study
  • other organic gastrointestinal diseases (i.e. careful exclusion of Crohn's disease)
  • concomitant treatment with steroids and/or antihistamines.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antonio Carroccio, PhD +390916552884 acarroccio@hotmail.com
Contact: Pasquale Mansueto, MD +390916552884 pasquale.mansueto@unipa.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03024775
Other Study ID Numbers  ICMJE ACPM16
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Pasquale Mansueto, University of Palermo
Study Sponsor  ICMJE University of Palermo
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Antonio Carroccio, PhD University of Palermo
PRS Account University of Palermo
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP