Clinical trial NCT03022513: Fibromyalgia-like Joint/Muscle Pain and Synovitis in Non-celiac Wheat Sensitivity Patients
Official title: Fibromyalgia-like Joint/Muscle Pain and Synovitis in Non-celiac Wheat Sensitivity Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-celiac Wheat Sensitivity
Keywords: Non-celiac Wheat Sensitivity
fibromyalgia
synovitis
Lead sponsor: University of Palermo
Sponsor class: OTHER
First posted: 2017-01-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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. The clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal and/or systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Nowadays no data are available on the characteristic of 'rheumatologic' symptoms of NCWS patients. Therefore, the aims of the present study are: 1) to investigate the prevalence of fibromyalgia-like joint/muscle pain in NCWS patient, 2) to search for possible ultrasonographic alterations (i.e. synovitis) of hands and feet joints of NCWS patients, and 3) to evaluate modification of fibromyalgia-like joint/muscle pain in NCWS patients after a gluten free diet period of almost 6 months.

Detailed description: 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. CD is an immunological disorder whose best-known manifestations are gastrointestinal symptoms. However, early joint manifestations are common and frequently overlooked features of the disease. Similarly, the clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal and/or systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Nowadays no data are available on the characteristic of 'rheumatological' symptoms of NCWS patients. Therefore, the aims of the present study are: 1) to investigate the prevalence of fibromyalgia-like joint/muscle pain in NCWS patient, 2) to search for possible ultrasonographical alterations (i.e. synovitis) of hands and feet joints of NCWS patients, and 3) to evaluate modification of fibromyalgia-like joint/muscle pain in NCWS patients after a gluten free diet period of almost 6 months.

Eligibility criteria: Inclusion Criteria:

All the patients met 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 and cow's milk protein (skin prick tests and/or serum specific IgE detection).

Adjunctive criteria adopted in our patients were:

* resolution of the gastrointestinal and extra-intestinal 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 double-blind placebo-controlled (DBPC) wheat challenge, performed as described previously. DBPC cow's milk protein challenge will be also performed to diagnose cow's milk protein allergy.

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
* previously diagnosed rheumatic diseases
* 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: Prevalence of fibromyalgia-like joint/muscle pain in NCWS patients
timeFrame: up to 12 months
measure: Hands and feet joints ultrasonography alterations
timeFrame: up to 12 months
Secondary outcomes:
measure: Modification of fibromyalgia-like joint/muscle pain in NCWS patients after gluten free diet
timeFrame: up to 12 months
measure: Modifications of hands and feet joints ultrasonography alterations in NCWS patients after gluten free diet
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Sciacca
country: Italy
facility: Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
state: Agrigento
city: Palermo
country: Italy
facility: Department of Internal Medicine, University Hospital of Palermo
Study officials:
affiliation: University of Palermo
name: Antonio Carroccio, PhD
role: STUDY_DIRECTOR
References:
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: 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, 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. 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.