Anemia in Non-celiac Wheat Sensitivity

NCT ID: NCT04377061

Last Updated: 2022-02-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

244 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-01

Study Completion Date

2022-01-01

Brief Summary

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In recent years, a new gluten- or wheat-related disease has emerged, a condition labelled "non-celiac gluten sensitivity" (NCGS) or "non-celiac wheat sensitivity" (NCWS). This is very often a self-reported condition, since patients refer to intestinal \[mainly irritable bowel syndrome (IBS)-like\] and/or extra-intestinal symptoms (i.e. fatigue, headache, anemia) caused by gluten or wheat ingestion, even though they do not suffer from celiac disease (CD) or wheat allergy (WA).

Among the extra-intestinal symptoms, several studies have shown, in patients with NCWS, the presence of anemia, generally mild, often with iron or folate deficiency characteristics, but no research has ever been planned with the specific intention of analyze this particular aspect of the disease.

Therefore, the aim of the present multicentric research was to analyze, both retrospectively and prospectively, the laboratory data of NCWS patients, compared to CD and IBS controls, to identify: a) the presence, severity and morphologic characteristic of anemia; 2) possible pathogenic mechanisms.

Detailed Description

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In recent years, a new gluten- or wheat-related disease has emerged, a condition labelled "non-celiac gluten sensitivity" (NCGS) or "non-celiac wheat sensitivity" (NCWS). This is very often a self-reported condition, since patients refer to intestinal \[mainly irritable bowel syndrome (IBS)-like\] and/or extra-intestinal symptoms (i.e. fatigue, headache, anemia) caused by gluten or wheat ingestion, even though they do not suffer from celiac disease (CD) or wheat allergy (WA).

There are conflicting data about the real mechanisms which induce symptoms in NCGS/NCWS patients after wheat ingestion. Some authors suggested a prevalent role for Fermentable Oligosaccharides-Disaccharides-Monosaccharides and Polyols (FODMAPs), rather than gluten in determining the symptoms. Other studies underlined the activation of mechanisms of both innate and acquired immunity in NCWS patients after wheat ingestion.

Given the lack of a diagnostic biomarker, NCGS/NCWS mostly remains a diagnosis of exclusion, especially respect to CD and WA, so a confirmatory test is required. The "Salerno criteria" suggested the double-blind, placebo-controlled (DBPC), cross-over, gluten/wheat challenge as the gold standard test to discriminate true NCGS/NCWS patients.

By definition, NCGS/NCWS symptoms generally occur after the ingestion of gluten/wheat, disappear within a few days of a gluten-free diet (GFD) and quickly reappear when gluten/wheat is, voluntarily or accidentally, reintroduced. However, GDF is very difficult and onerous from a social (presence of gluten in many industrial food products and "contamination", both domestic and extra-domestic), psychological (e.g. for adolescents, exclusion from the "peer group", with difficulty in accepting the diagnosis) and economic point of view.

Among the extra-intestinal symptoms, several studies have shown, in patients with NCWS, the presence of anemia, generally mild, often with iron or folate deficiency characteristics, but no research has ever been planned with the specific intention of analyze this particular aspect of the disease.

Therefore, the aim of the present multicentric research was to analyze, both retrospectively and prospectively, the laboratory data of NCWS patients, compared to CD and IBS controls, to identify: a) the presence, severity and morphologic characteristic of anemia; 2) possible pathogenic mechanisms, with particular attention to iron, vitamin B12 and folate metabolism, thyroid hormones, and autoimmune gastric involvement.

Conditions

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Non-celiac Gluten Sensitivity Anemia

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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NCWS retrospective and prospective patients

The clinical charts of NCWS patients, diagnosed by DBPC gluten/wheat challenge, between January 2001 and December 2019, attending the Department of Internal Medicine at the University Hospital of Palermo, the Department of Internal Medicine of the Hospital of Sciacca, and the Department of Medical and Surgical Sciences of the University of Bologna, will be reviewed retrospectively. The investigators prospectively will also survey patients with functional gastroenterological symptoms according to the Rome III criteria, and a definitive diagnosis of NCWS by DBPC gluten/wheat challenge. The patients will be recruited between January 2019 and January 2022 at the same centers, and at the Internal Medicine Division of the "Cervello-Villa Sofia" Hospital of Palermo, Palermo.

Evaluation of anemia

Intervention Type DIAGNOSTIC_TEST

Evaluation of anemia in NCWS patients, and in CD and IBS controls, with both retrospective and prospective method.

CD retrospective and prospective control patients

To compare the presence and characteristics of anemia in NCWS patients, the clinical charts of a control group of CD patients had been randomly chosen by a computer-generated method from patients diagnosed in the same centers, during the same period (2001-2019), and age- and sex-matched with the NCWS patients. The investigators prospectively will also survey a control group of CD patients randomly chosen by a computer-generated method from subjects diagnosed in the same centers, during the same period (2019-2022), and age- and sex-matched with the NCWS patients.

Evaluation of anemia

Intervention Type DIAGNOSTIC_TEST

Evaluation of anemia in NCWS patients, and in CD and IBS controls, with both retrospective and prospective method.

IBS retrospective and prospective control patients

To compare the presence and characteristics of anemia in NCWS patients, the clinical charts of another control group of IBS patients had been randomly chosen by a computer-generated method from patients diagnosed in the same centers, during the same period (2001-2019), and age- and sex-matched with the NCWS patients. The investigators prospectively will also survey a control group of IBS patients randomly chosen by a computer-generated method from subjects diagnosed in the same centers, during the same period (2019-2022), and age- and sex-matched with the NCWS patients.

Evaluation of anemia

Intervention Type DIAGNOSTIC_TEST

Evaluation of anemia in NCWS patients, and in CD and IBS controls, with both retrospective and prospective method.

Interventions

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Evaluation of anemia

Evaluation of anemia in NCWS patients, and in CD and IBS controls, with both retrospective and prospective method.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. To diagnose CD the standard criteria will be adopted. All the patients will meet the following criteria:

\- positive serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) immunoglobulin (Ig)A and IgG antibodies presence of intestinal villous atrophy.
3. To diagnose IBS the standard Rome II (for retrospective patients) and Rome III (for prospective patients) Criteria will be adopted. None of these subjects improved on an elimination diet without wheat, cow's milk, egg, tomato, or chocolate.

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 previously diagnosed gastrointestinal disorders, other previously diagnosed gynaecological disorders, nervous system disease and/or major psychiatric disorder, physical impairment limiting physical activity.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Palermo

OTHER

Sponsor Role lead

Responsible Party

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Pasquale Mansueto

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pasquale Mansueto, MD

Role: PRINCIPAL_INVESTIGATOR

University of Palermo

Locations

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Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca

Sciacca, Agrigento, Italy

Site Status

Internal Medicine Division of the "Cervello-Villa Sofia" Hospital

Palermo, PA, Italy

Site Status

Department of Internal Medicine, University Hospital of Palermo

Palermo, , Italy

Site Status

Countries

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Italy

References

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Mansueto P, Soresi M, La Blasca F, Fayer F, D'Alcamo A, Carroccio A. Body Mass Index and Associated Clinical Variables in Patients with Non-Celiac Wheat Sensitivity. Nutrients. 2019 May 29;11(6):1220. doi: 10.3390/nu11061220.

Reference Type RESULT
PMID: 31146428 (View on PubMed)

Carroccio A, Giannone G, Mansueto P, Soresi M, La Blasca F, Fayer F, Iacobucci R, Porcasi R, Catalano T, Geraci G, Arini A, D'Alcamo A, Villanacci V, Florena AM. Duodenal and Rectal Mucosa Inflammation in Patients With Non-celiac Wheat Sensitivity. Clin Gastroenterol Hepatol. 2019 Mar;17(4):682-690.e3. doi: 10.1016/j.cgh.2018.08.043. Epub 2018 Aug 21.

Reference Type RESULT
PMID: 30138736 (View on PubMed)

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.

Reference Type RESULT
PMID: 26026392 (View on PubMed)

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.

Reference Type RESULT
PMID: 25430806 (View on PubMed)

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.

Reference Type RESULT
PMID: 24533607 (View on PubMed)

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.

Reference Type RESULT
PMID: 24275240 (View on PubMed)

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.

Reference Type RESULT
PMID: 22825366 (View on PubMed)

Volta U, De Giorgio R, Caio G, Uhde M, Manfredini R, Alaedini A. Nonceliac Wheat Sensitivity: An Immune-Mediated Condition with Systemic Manifestations. Gastroenterol Clin North Am. 2019 Mar;48(1):165-182. doi: 10.1016/j.gtc.2018.09.012. Epub 2018 Dec 13.

Reference Type RESULT
PMID: 30711208 (View on PubMed)

Uhde M, Ajamian M, Caio G, De Giorgio R, Indart A, Green PH, Verna EC, Volta U, Alaedini A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016 Dec;65(12):1930-1937. doi: 10.1136/gutjnl-2016-311964. Epub 2016 Jul 25.

Reference Type RESULT
PMID: 27459152 (View on PubMed)

Volta U, Pinto-Sanchez MI, Boschetti E, Caio G, De Giorgio R, Verdu EF. Dietary Triggers in Irritable Bowel Syndrome: Is There a Role for Gluten? J Neurogastroenterol Motil. 2016 Oct 30;22(4):547-557. doi: 10.5056/jnm16069.

Reference Type RESULT
PMID: 27426486 (View on PubMed)

Volta U, Caio G, De Giorgio R. Is Autoimmunity More Predominant in Nonceliac Wheat Sensitivity Than Celiac Disease? Gastroenterology. 2016 Jan;150(1):282. doi: 10.1053/j.gastro.2015.08.058. Epub 2015 Nov 23. No abstract available.

Reference Type RESULT
PMID: 26616572 (View on PubMed)

De Giorgio R, Volta U, Gibson PR. Sensitivity to wheat, gluten and FODMAPs in IBS: facts or fiction? Gut. 2016 Jan;65(1):169-78. doi: 10.1136/gutjnl-2015-309757. Epub 2015 Jun 15.

Reference Type RESULT
PMID: 26078292 (View on PubMed)

Di Sabatino A, Volta U, Salvatore C, Biancheri P, Caio G, De Giorgio R, Di Stefano M, Corazza GR. Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial. Clin Gastroenterol Hepatol. 2015 Sep;13(9):1604-12.e3. doi: 10.1016/j.cgh.2015.01.029. Epub 2015 Feb 19.

Reference Type RESULT
PMID: 25701700 (View on PubMed)

Caio G, Volta U, Tovoli F, De Giorgio R. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity. BMC Gastroenterol. 2014 Feb 13;14:26. doi: 10.1186/1471-230X-14-26.

Reference Type RESULT
PMID: 24524388 (View on PubMed)

Other Identifiers

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ACPM25

Identifier Type: -

Identifier Source: org_study_id

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