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Not-celiac Wheat Sensitivity (NCWS)NCT03563300

Gluten-related Disorders in Familial Mediterranean Fever Patients

A study testing Wheat flour in people with Not-celiac Wheat Sensitivity (NCWS) and Familial Mediterranean Fever (FMF), run by University of Palermo at 2 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Wheat flour
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
8 participants
Where
2 sitesItaly
Study dates
1 Sep 2018to 1 Apr 2019
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

Italy2 sites
  • Department of Internal Medicine, University Hospital of Palermo

    Palermo, 90129

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

    Sciacca, Agrigento, 92019

Other trials in Italy

About this study

Official title: Gluten-related Disorders in Patients Affected With Familial Mediterranean Fever

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.

Read the detailed description

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. It is characterized by intestinal (i.e. irritable bowel syndrome, bloating, dyspepsia) and extra-intestinal symptoms (i.e. fatigue, headache, numbness, mental confusion) 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. In fact, in previous studies the investigators showed that patients self-reporting gastrointestinal symptoms related to wheat ingestion, could suffer not only from CD or WA, but from small intestinal bacterial overgrowth or inflammatory bowel diseases also. 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). Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease, characterized by self-limited recurrent attacks of fever and serositis, resulting in pain in the abdomen, chest, joints and muscles. FMF is caused by mutations in MEFV gene, which encodes pyrin. Pyrin is implicated in a complex interplay with proteins involved in Toll-like receptor (TLR) signalling, PYD superfamily and procaspase-1 activation, suggesting a controlling role in inflammatory response. Abdominal pain is the most frequent symptom encountered in FMF; 95% of patients report this as the main symptom during at least some of their fever episodes, while 50% cite such an 'abdominal attack' as the first symptom of their disease. Presentation of a typical abdominal attack will resemble that of 'acute abdomen'. Onset is sudden and acute, leading to rapid development of symptoms within 1-2 hours. The abdominal pain is usually diffuse throughout the entire abdomen, although in some cases it may be localized; it may be very severe in intensity. This may be accompanied by any bowel activity, ranging from constipation (most often) to diarrhoea. The intensity of symptoms and signs of an inflammatory attack in FMF will decrease spontaneously after 12-24 hours, and usually, the attack resolves over the following 48 hours. Thus, after about 3 days the patient will be symptom-free again. Furthermore, so-called "incomplete" abdominal attacks may occur in FMF patients. These differ from 'typical' abdominal attacks in 1 or 2 features, which may include absence of fever, absence of 'true' peritonitis and/or localisation of the abdominal pain to a single specific abdominal area, minimal change in acute phase parameters. It may be difficult to differentiate an 'incomplete' abdominal attack from other causes of abdominal pain, mainly because of its atypical presentation. 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. However, to our knowledge, a relationship between FMF and NCGS has not been previously investigated. 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. The study will be done after a period of gluten-free diet, administering wheat flour or placebo for 15 days. 2. To identify possible immunologic markers (histological features, expression of cytokines and other constitutive mucosal proteins from peripheral blood mononuclear cells and mucosal lymphocytes) that may explain the mechanism underling FMF abdominal attack and wheat ingestion.

Being tested
Wheat flour, Placebo Comparator
Medical subject headings
Familial Mediterranean Fever

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Wheat flourOther

    Also called Active Comparator

    Wheat flour will be administered once daily for 7 days

  • Placebo ComparatorOther

    Also called Rice flour

    Placebo will be administered blindly versus wheat flour for 7 days

Study groups in NCT03563300
Study groupRoleWhat they receive
Wheat flourActive comparatorWheat flour will be administered blindly versus placebo for 7 days
Receives: Other: Wheat flour
Rice flourPlacebo comparatorPlacebo will be administered blindly versus wheat flour for 7 days
Receives: Other: Placebo Comparator

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Change from baseline at 1 week

  2. 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

    Measured: Change from baseline at 1 week

Secondary outcomes (2)
  1. Leukocytes cell surface antigens expression

    There will be evaluated some leukocytes cell surface antigens expression, i.e. CD45, CD56, CD117, NKp44, CD3, CD19, and CD14, from peripheral blood mononuclear cells and rectal mucosal lymphocytes before and after 1 week of wheat (or placebo) ingestion

    Measured: Change from baseline at 1 week

  2. Cytokines production

    There will be evaluated some cytokines production, i.e. IFN-γ, TNF-α, IL-22, IL-17, and T-bet, from peripheral blood mononuclear cells and rectal mucosal lymphocytes before and after 1 week of wheat (or placebo) ingestion

    Measured: Change from baseline at 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2018
  2. Study start1 Sep 2018
  3. Primary completion1 Mar 2019
  4. Study completion1 Apr 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel Assignment
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03563300
Sponsor's protocol ID
ACPM21
Status last verified
Apr 2019
First submitted
24 May 2018
Last updated
17 Apr 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 22825366
  • 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.

    PubMed 24169272
  • 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.

    PubMed 24275240
  • 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.

    PubMed 24533607
  • 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.

    PubMed 26026392
  • 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.

    PubMed 27388423
  • 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.

    PubMed 26823530
  • 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.

    PubMed 3123181

Questions about this trial

What is this clinical trial studying?

A study testing Wheat flour in people with Not-celiac Wheat Sensitivity (NCWS) and Familial Mediterranean Fever (FMF), run by University of Palermo at 2 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fibromyalgia symptoms evaluation (time frame: Change from baseline at 1 week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03563300, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2019.

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