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Fibromyalgia-like Joint/Muscle Pain and Synovitis in Non-celiac Wheat Sensitivity Patients

Primary Purpose

Non-celiac Wheat Sensitivity

Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Gluten free diet
Sponsored by
University of Palermo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Non-celiac Wheat Sensitivity focused on measuring Non-celiac Wheat Sensitivity, fibromyalgia, synovitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
  • Department of Internal Medicine, University Hospital of Palermo

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

No Intervention

No Intervention

Arm Label

NCWS patients

CD patients

IBS patients

Arm Description

Fifty consecutive adult patients with an irritable bowel syndrome (IBS)-like clinical presentation, according to Rome III criteria, and a definitive diagnosis of NCWS. The patients will be recruited between January 2017 and January 2018 at 2 centers: the Department of Internal Medicine at the University Hospital of Palermo, Italy, and the Department of Internal Medicine of the Hospital of Sciacca, Agrigento, Italy. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy.

Fifty sex- and age-matched subjects with CD, diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as first control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy.

Fifty 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, at the same 2 centers, as second control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo.

Outcomes

Primary Outcome Measures

Prevalence of fibromyalgia-like joint/muscle pain in NCWS patients
Prevalence of fibromyalgia-like joint/muscle pain in NCWS patient using an ad hoc questionnaire and orientated clinical examination (tenders and triggers point evaluation)
Hands and feet joints ultrasonography alterations
Hands and feet joints ultrasonography alterations in NCWS patients.

Secondary Outcome Measures

Modification of fibromyalgia-like joint/muscle pain in NCWS patients after gluten free diet
Modification of fibromyalgia-like joint/muscle pain, by visual analogic scale, in NCWS patients after a gluten free diet period of almost 6 months.
Modifications of hands and feet joints ultrasonography alterations in NCWS patients after gluten free diet
Modifications of hands and feet joints ultrasonography alterations in NCWS patients after a gluten free diet period of almost 6 months.

Full Information

First Posted
December 30, 2016
Last Updated
April 26, 2020
Sponsor
University of Palermo
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1. Study Identification

Unique Protocol Identification Number
NCT03022513
Brief Title
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

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
March 1, 2018 (Actual)
Primary Completion Date
June 1, 2018 (Actual)
Study Completion Date
March 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Palermo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-celiac Wheat Sensitivity
Keywords
Non-celiac Wheat Sensitivity, fibromyalgia, synovitis

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NCWS patients
Arm Type
Active Comparator
Arm Description
Fifty consecutive adult patients with an irritable bowel syndrome (IBS)-like clinical presentation, according to Rome III criteria, and a definitive diagnosis of NCWS. The patients will be recruited between January 2017 and January 2018 at 2 centers: the Department of Internal Medicine at the University Hospital of Palermo, Italy, and the Department of Internal Medicine of the Hospital of Sciacca, Agrigento, Italy. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy.
Arm Title
CD patients
Arm Type
No Intervention
Arm Description
Fifty sex- and age-matched subjects with CD, diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as first control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy.
Arm Title
IBS patients
Arm Type
No Intervention
Arm Description
Fifty 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, at the same 2 centers, as second control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo.
Intervention Type
Other
Intervention Name(s)
Gluten free diet
Intervention Description
The investigators will evaluate the prevalence of fibromyalgia-like joint/muscle pain and the possible ultrasonographical alterations (i.e. synovitis) of hands and feet joints in NCWS patient at baseline (i.e. at the moment of diagnosis) and after a gluten free diet period of almost 6 months.
Primary Outcome Measure Information:
Title
Prevalence of fibromyalgia-like joint/muscle pain in NCWS patients
Description
Prevalence of fibromyalgia-like joint/muscle pain in NCWS patient using an ad hoc questionnaire and orientated clinical examination (tenders and triggers point evaluation)
Time Frame
up to 12 months
Title
Hands and feet joints ultrasonography alterations
Description
Hands and feet joints ultrasonography alterations in NCWS patients.
Time Frame
up to 12 months
Secondary Outcome Measure Information:
Title
Modification of fibromyalgia-like joint/muscle pain in NCWS patients after gluten free diet
Description
Modification of fibromyalgia-like joint/muscle pain, by visual analogic scale, in NCWS patients after a gluten free diet period of almost 6 months.
Time Frame
up to 12 months
Title
Modifications of hands and feet joints ultrasonography alterations in NCWS patients after gluten free diet
Description
Modifications of hands and feet joints ultrasonography alterations in NCWS patients after a gluten free diet period of almost 6 months.
Time Frame
up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Carroccio, PhD
Organizational Affiliation
University of Palermo
Official's Role
Study Director
Facility Information:
Facility Name
Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
City
Sciacca
State/Province
Agrigento
ZIP/Postal Code
92019
Country
Italy
Facility Name
Department of Internal Medicine, University Hospital of Palermo
City
Palermo
ZIP/Postal Code
90129
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22825366
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.
Results Reference
result
PubMed Identifier
24533607
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.
Results Reference
result
PubMed Identifier
24275240
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.
Results Reference
result
PubMed Identifier
25625764
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.
Results Reference
result
PubMed Identifier
25430806
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.
Results Reference
result
PubMed Identifier
25694210
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.
Results Reference
result

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Fibromyalgia-like Joint/Muscle Pain and Synovitis in Non-celiac Wheat Sensitivity Patients

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