Osteoporosis In Non-Celiac Wheat Sensitivity Patients

Sponsor

University of Palermo (Other)

Overall Status

Completed

CT.gov ID

NCT02421783

Collaborator

(none)

270

Enrollment

Locations

Actual Duration (Months)

135

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-celiac Wheat Sensitivity

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.

Study Design

Study Type:

Observational

Actual Enrollment :

270 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Osteoporosis In Non-Celiac Wheat Sensitivity Patients

Actual Study Start Date :

May 1, 2015

Actual Primary Completion Date :

Oct 1, 2016

Actual Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
NCWS patients Consecutive adult patients with an irritable bowel syndrome (IBS)-like clinical presentation, according to Rome II criteria, and a definitive diagnosis of NCWS.
CD patients Sex- and age-matched subjects with CD, diagnosed according to standard criteria during the same study period and enrolled as first control group
IBS patients Sex- and age-matched subjects with IBS unrelated to NCWS or other food 'intolerance', diagnosed according to standard criteria during the same study period and enrolled as second control group

Outcome Measures

Primary Outcome Measures

Change in bone mineral density (BMD) [At baseline and at 24 months]
BMD will be assessed by dual x-ray absorptiometry (DXA), using a QDR Discovery Hologic DXA scanner in the femoral neck and in the lumbar spine. For each scan, BMD and T-scores will be recorded. A T-score between +1 and -1 is considered normal, between -1 and -2.5 indicates osteopenia, -2.5 or lower indicates osteoporosis. The investigators also will calculate the 10-year fracture risks according to the standardized WHO FRAX equation, computed with BMD (T-score) at the femoral neck.

Secondary Outcome Measures

Conventional lateral spine x-ray as an assessment of suspected osteoporotic vertebral fractures, using Genant's method [At baseline]
A random sample of the patients and controls will undergo conventional lateral spine x-ray for better assessment of suspected osteoporotic vertebral fractures, according to Genant's method (grade 0, no reduction; grade 1, minimal fracture, 20-25% vertebral height decrease; grade 2, moderate fracture, 25-40% vertebral height decrease; and grade 3, severe fracture, greater than 40% vertebral height decrease).
Change in serum bone alkaline phosphatase [At baseline and at 24 months]
Serum bone alkaline phosphatase values will be detected (refences values of adults males < or =20 mcg/L; of adults premenopausal females < or =14 mcg/L; of adults postmenopausal females < or =22 mcg/L).
Change in serum 25-hydroxyvitamin D [At baseline and at 24 months]
Serum 25-hydroxyvitamin D values will be detected (refences values 30.0-74.0 ng/mL).
Change in serum phosphorus levels [At baseline and at 24 months]
Serum phosphorus levels values will be detected (refences values of subjects > or =18 years: 2.5-4.5 mg/dL).
Change in serum calcium levels [At baseline and at 24 months]
Serum calcium levels values will be detected (refences values of males age 18-21 years: 9.3-10.3 mg/dL, age 22 years and older: 8.9-10.1 mg/dL; of females age 18 years and older: 8.9-10.1 mg/dL)
Change in urinary phosphorus levels [At baseline and at 24 months]
Urinary phosphorus levels values will be detected (refences values 0.4-1.3 g per 24-hour urine sample).
Change in urinary calcium levels [At baseline and at 24 months]
Urinary calcium levels values will be detected (refences values 100-300 mg per 24-hour urine sample).
Change in dietary intake and lifestyle [At baseline and at 24 months]
All the participants will fill in a health and lifestyle questionnaire, considering menarche and age at menopause (if applicable), medical and drug abuse history, lifestyle habits (including elimination diet, smoking status, alcohol consumption, Italian espresso coffee drinking and physical activity); history of bone fractures will also be recorded. In order to assess daily caloric intake and calcium intake, the subjects will receive a dietary form containing a printed list of the most common foods.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.