Gluten-related Disorders in Familial Mediterranean Fever Patients

NCT03563300 | Completed

• 1 other identifier: ACPM21
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

It is known that the gluten-containing grains can be responsible for human diseases related to gluten exposure. These forms of gluten intolerance represent a heterogeneous set of conditions, including celiac disease (CD), wheat allergy (WA) and not celiac gluten sensitivity (NCGS), that combined seems to affect about 5-10% of the general population. NCGS is the most recent gluten-related disease, characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects in whom either celiac disease or wheat allergy previously has been excluded. However, as it is not known what component of the cereals causes the symptoms in NCGS patients, the investigators prefer the label of "Not-celiac wheat sensitivity" (NCWS). Typically, the NCWS diagnosis is made by exclusion. Furthermore, similarly to CD, the investigators had demonstrated that NCWS may be associated with other autoimmune disease (i.e. Hashimoto's thyroiditis). Among these autoimmune conditions, in our daily out clinic work, the investigators have observed an association between self-reported NCWS and Familial Mediterranean Fever (FMF). Our preliminary observational data indicate that some FMF patients relate their symptoms (especially gastrointestinal) to gluten assumption, then excluding it from diet and using gluten-free products, with partial remission of gastrointestinal symptoms. Therefore, FMF and NCGS share some clinical features, such as abdominal pain, diarrhea, arthralgia and arthritis, and tend to be commonly associated with other inflammatory and autoimmune diseases. This study has 2 major aims: 1.To evaluate the real relationship between the wheat ingestion and the gastrointestinal manifestations presented by FMF patients, self-reporting a NCWS. 2. To identify possible immunologic markers that may explain the mechanism underling FMF abdominal attack and wheat ingestion.

Conditions

Not-celiac Wheat Sensitivity (NCWS); Familial Mediterranean Fever (FMF)

Outcome Measures

Primary Outcomes (2)

• Fibromyalgia symptoms evaluation

  Fibromyalgia symptoms of patients, evaluated by the International Severity Scoring System for Familial Mediterranean Fever (ISSF), will be scored before and after 1 week of wheat (or placebo) ingestion

  Change from baseline at 1 week

• Gastrointestinal symptoms evaluation

  Gastrointestinal symptoms of patients, evaluated by the Gastrointestinal Symptom Rating Scale (GSRS), will be scored before and after 1 week of wheat (or placebo) ingestion

  Change from baseline at 1 week

Secondary Outcomes (2)

• Leukocytes cell surface antigens expression

  Change from baseline at 1 week

• Cytokines production

  Change from baseline at 1 week

Study Arms (2)

Wheat flour

ACTIVE COMPARATOR

Wheat flour will be administered blindly versus placebo for 7 days

Other: Wheat flour

Rice flour

PLACEBO COMPARATOR

Placebo will be administered blindly versus wheat flour for 7 days

Other: Placebo Comparator

Interventions

Wheat flour OTHER

Wheat flour will be administered once daily for 7 days

Also known as: Active Comparator

Wheat flour

Placebo Comparator OTHER

Placebo will be administered blindly versus wheat flour for 7 days

Also known as: Rice flour

Rice flour

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients, both genders, with age between 18-65 years, affected with FMF, diagnosed according to clinical criteria designed by Livneh et al ("Tel-Hashomer" criteria), self-reporting a relationship between their symptoms (especially gastrointestinal) and gluten assumption, improving on a gluten-free diet and worsen on a gluten containing diet
• Patients testing negative for celiac disease (anti-tTG and EMA negative, and with biopsy Marsh 0-1) and wheat allergy (serum specific IgE for wheat negative)

You may not qualify if:

• Subjects diagnosed with celiac disease (positive anti-tTG and/or EMA, and positive histology, with Marsh 2 or above);
• Subjects diagnosed with wheat allergy (positive serum specific IgE for wheat)
• Subjects with Inflammatory Bowel Diseases (Crohn's disease or ulcerative colitis)
• Subjects with Helicobacter pylori infection and other gastrointestinal infection
• Pregnancy

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (2)

Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca

Sciacca, Agrigento, 92019, Italy

Location

Department of Internal Medicine, University Hospital of Palermo

Palermo, 90129, Italy

Location

Related Publications (8)

• 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.

  PMID: 22825366 RESULT

• 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.

  PMID: 24169272 RESULT

• 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.

  PMID: 24275240 RESULT

• 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.

  PMID: 24533607 RESULT

• Carroccio A, D'Alcamo A, Cavataio F, Soresi M, Seidita A, Sciume C, Geraci G, Iacono G, Mansueto P. High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies. Gastroenterology. 2015 Sep;149(3):596-603.e1. doi: 10.1053/j.gastro.2015.05.040. Epub 2015 May 27.

  PMID: 26026392 RESULT

• Di Liberto D, Mansueto P, D'Alcamo A, Lo Pizzo M, Lo Presti E, Geraci G, Fayer F, Guggino G, Iacono G, Dieli F, Carroccio A. Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet. Clin Transl Gastroenterol. 2016 Jul 7;7(7):e178. doi: 10.1038/ctg.2016.35.

  PMID: 27388423 RESULT

• Demirkaya E, Acikel C, Hashkes P, Gattorno M, Gul A, Ozdogan H, Turker T, Karadag O, Livneh A, Ben-Chetrit E, Ozen S; FMF Arthritis Vasculitis and Orphan disease Research in pediatric rheumatology (FAVOR). Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis. 2016 Jun;75(6):1051-6. doi: 10.1136/annrheumdis-2015-208671. Epub 2016 Jan 28.

  PMID: 26823530 RESULT

• Svedlund J, Sjodin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988 Feb;33(2):129-34. doi: 10.1007/BF01535722.

  PMID: 3123181 RESULT

MeSH Terms

Conditions

Familial Mediterranean Fever

Interventions

Flour

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Antonio Carroccio, PhD

  University of Palermo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 20, 2018
• Study Start: September 1, 2018
• Primary Completion: March 1, 2019
• Study Completion: April 1, 2019
• Last Updated: April 17, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)