Clinical trial NCT02421783: Osteoporosis In Non-Celiac Wheat Sensitivity Patients
Official title: Osteoporosis In Non-Celiac Wheat Sensitivity Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non-celiac Wheat Sensitivity
Keywords: Non-celiac wheat sensitivity
Multiple food allergy
Body mass index
Osteoporosis
Lead sponsor: University of Palermo
Sponsor class: OTHER
First posted: 2015-04-21
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will include consecutive adult patients with irritable bowel syndrome (IBS)-like clinical presentation, according to Rome II criteria, and a definitive diagnosis of NCWS, referred at the Internal Medicine and at the Gastroenterology Units of the University Hospital of Palermo, between may 2015 and may 2017.

Brief summary: Non-celiac gluten sensitivity (NCGS) or 'wheat sensitivity' (NCWS) is included in the spectrum of gluten-related disorders. No data are available on the prevalence of low bone mass density (BMD) in NCWS. Our study aims to evaluate the prevalence of low BMD in NCWS patients and search for correlations with other clinical characteristics.

This prospective observation study will include 90 NCWS patients with irritable bowel syndrome (IBS)-like symptoms, 90 IBS and 90 celiac controls. Patients will be recruited at the Internal Medicine and at the Gastroenterology Units of the University of Palermo. Elimination diet and double-blind placebo controlled (DBPC) wheat challenge proved the NCWS diagnosis. All subjects underwent BMD assessment by Dual Energy X-Ray Absorptiometry (DXA), duodenal histology, Human Leukocyte Antigen (HLA) DQ typing, body mass index (BMI) evaluation and assessment for daily calcium intake.

Detailed description: Celiac disease (CD) has been reported to increase the risk of osteoporosis, with a resulting augmented risk of fractures. More recently, it has been reported that a consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term 'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes the symptoms in NCGS patients, and the investigators also showed that these patients had a high frequency of coexistent multiple food hypersensitivity. That previous study also showed a percentage of NCWS patients had weight loss and anemia: whether these depended on the intestinal malabsorption or not remains unclear. As yet no data are available on the presence and prevalence of low bone mass density (BMD) in NCWS patients. The aims of the present study is: 1) to investigate the prevalence of low BMD in NCWS patient and 2) to search for a possible correlation between BMD and other clinical characteristics, in particular the body mass index (BMI), of NCWS patients.

Eligibility criteria: Inclusion Criteria:

To diagnose NCWS the recently proposed criteria will be adopted. All the patients will meet the following criteria:

* negative serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) immunoglobulin (Ig)A and IgG antibodies;
* absence of intestinal villous atrophy;
* negative IgE-mediated immune-allergy tests to wheat (skin prick tests and/or serum specific IgE detection);
* resolution of the IBS symptoms on standard elimination diet, excluding wheat, cow's milk, egg, tomato, chocolate, and other self-reported food(s) causing symptoms;
* symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge. As the investigators previously described in other studies, DBPC cow's milk protein challenge and other "open" food challenges will be performed too.

Additional inclusion criteria will be:

* age \>18 years; follow-up duration longer than six months after the initial diagnosis;
* at least two outpatient visits during the follow-up period.

Exclusion Criteria:

* positive EmA in the culture medium of the duodenal biopsies, also in the case of normal villi/crypts ratio in the duodenal mucosa;
* self-exclusion of wheat from the diet and refusal to reintroduce it, before entering the study;
* other "organic" gastrointestinal disorders;
* nervous system disease and/or major psychiatric disorder;
* physical impairment limiting physical activity;
* menopause;
* steroid and sex steroid therapy, hormone replacement therapy or ovariectomy.

Primary outcomes:
measure: Change in bone mineral density (BMD)
timeFrame: At baseline and at 24 months
Secondary outcomes:
measure: Conventional lateral spine x-ray as an assessment of suspected osteoporotic vertebral fractures, using Genant's method
timeFrame: At baseline
measure: Change in serum bone alkaline phosphatase
timeFrame: At baseline and at 24 months
measure: Change in serum 25-hydroxyvitamin D
timeFrame: At baseline and at 24 months
measure: Change in serum phosphorus levels
timeFrame: At baseline and at 24 months
measure: Change in serum calcium levels
timeFrame: At baseline and at 24 months
measure: Change in urinary phosphorus levels
timeFrame: At baseline and at 24 months
measure: Change in urinary calcium levels
timeFrame: At baseline and at 24 months
measure: Change in dietary intake and lifestyle
timeFrame: At baseline and at 24 months
Other outcomes:
Locations:
city: Sciacca
country: Italy
facility: Antonio Carroccio
state: Agrigento
city: Palermo
country: Italy
facility: Pasquale Mansueto
Study officials:
affiliation: Department of Internal Medicine, Giovanni Paolo II Hospital, Via Pompei, Sciacca, Italy
name: Antonio Carroccio, PhD
role: STUDY_DIRECTOR
References:
citation: Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Role of FODMAPs in Patients With Irritable Bowel Syndrome. Nutr Clin Pract. 2015 Oct;30(5):665-82. doi: 10.1177/0884533615569886. Epub 2015 Feb 18.
citation: Carroccio A, D'Alcamo A, Mansueto P. Nonceliac wheat sensitivity in the context of multiple food hypersensitivity: new data from confocal endomicroscopy. Gastroenterology. 2015 Mar;148(3):666-7. doi: 10.1053/j.gastro.2014.11.047. Epub 2015 Jan 24. No abstract available.
citation: Carroccio A, Soresi M, D'Alcamo A, Sciume C, Iacono G, Geraci G, Brusca I, Seidita A, Adragna F, Carta M, Mansueto P. Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study. BMC Med. 2014 Nov 28;12:230. doi: 10.1186/s12916-014-0230-2.
citation: Mansueto 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.
citation: 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.
citation: Carroccio A, Mansueto P, D'Alcamo A, Iacono G. Non-celiac wheat sensitivity as an allergic condition: personal experience and narrative review. Am J Gastroenterol. 2013 Dec;108(12):1845-52; quiz 1853. doi: 10.1038/ajg.2013.353. Epub 2013 Nov 5.
citation: 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.
citation: Carroccio A, Brusca I, Mansueto P, D'alcamo A, Barrale M, Soresi M, Seidita A, La Chiusa SM, Iacono G, Sprini D. A comparison between two different in vitro basophil activation tests for gluten- and cow's milk protein sensitivity in irritable bowel syndrome (IBS)-like patients. Clin Chem Lab Med. 2013 Jun;51(6):1257-63. doi: 10.1515/cclm-2012-0609.