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Anemia in Non-celiac Wheat Sensitivity

Clinical Characteristics and Pathogenic Mechanisms of Anemia in Non-celiac Wheat Sensitivity Compared to Celiac Disease and Irritable Bowel Syndrome

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT04377061
Enrollment
244
Registered
2020-05-06
Start date
2020-01-01
Completion date
2022-01-01
Last updated
2022-02-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anemia, Non-celiac Gluten Sensitivity

Keywords

Non-celiac Gluten Sensitivity, Anemia

Brief summary

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

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.

Interventions

DIAGNOSTIC_TESTEvaluation of anemia

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

Sponsors

University of Palermo
Lead SponsorOTHER

Study design

Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years

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

For NCWS diagnosis it will be evaluated the following

Design outcomes

Primary

MeasureTime frameDescription
Presence, severity and morphologic characteristic of anemiaAt baseline and at 24 monthsred blood cells (adults references ranges, RR, 4.5-5.9 million cells/mcL, men, 4.1-5.1 million cells/mcL, women), hemoglobin (RR 13-17 g/dL, men, 12-15 g/dL, women), hematocrit (RR 40%-52%, men, 36%-47%, women), mean corpuscular volume (RR 80-100 fL), mean corpuscular hemoglobin (RR 0.4-0.5 fmol/cell), mean corpuscular hemoglobin concentration (RR 30-35 g/dL), red cell distribution width (RR 11.5%-14.5%)

Secondary

MeasureTime frameDescription
Possible pathogenic mechanismsAt baseline and at 24 monthsreticulocytes count (RR 0.5%-1.5%), total serum iron (RR 65-180 µg/dL, men, 30-170 µg/dL, women), ferritin (RR 12-300 ng/mL, men, 12-150 ng/mL, women), transferrin (200-350 mg/dL), total iron-binding capacity (RR 45-85 µmol/L), vitamin B12 (RR 130-700 ng/L), folic acid (RR 7-36 nmol/L), thyroid-stimulating hormone (TSH, RR 2-10 μU/mL), anti-nuclear antibodies (ANA), anti-intrinsic factor (IFA) and/or parietal cell (APCA) antibodies

Countries

Italy

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026