Characteristics of Anemia in Celiac Disease

Celiac Disease Clinical Trial

Official title:

Clinical Characteristics and Pathogenic Mechanisms of Anemia in Celiac Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05172895
• Other study ID #: ACPM28
• Status: Completed
• Start date: January 1, 2001
• Est. completion date: July 31, 2021

Study information

• Verified date: December 2021
• Source: University of Palermo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Celiac Disease (CD) is an autoimmune disease involving the mucosa of the small intestine, triggered by the ingestion of gluten in genetically predisposed individuals. CD represents a global health problem. The clinical presentation of CD is characterized by a broad spectrum of both intestinal and extraintestinal manifestations, involving one or more organs. Anemia is one of the most common extraintestinal clinical manifestations of CD, present in more than half of adult patients at the time of diagnosis. Anemia in CD has a multifactorial pathogenesis: a) lack of absorption (or, sometimes, loss, as in the case of iron), of some micronutrients, such as iron, folate, vitamin B12, copper and zinc, b) coexistence of a chronic inflammatory state, as in the case of inflammatory bowel disease (IBD), c) refractory CD, d) medullary aplasia. The main purpose of this multicentre research is to evaluate, retrospectively, analyzing the clinical and laboratory data of CD patients, the presence, prevalence, severity, and morphological characteristics of anemia, trying to define, when possible, the underlying pathogenetic mechanisms, paying particular attention to the characteristics of menstrual cycles, the iron, folate and vitamin B12 metabolism, any chronic inflammatory state, and thyroid hormones. It will be also recorded, in a subgroup of the selected CD patients, any therapeutic responses (i.e., improvement/regression) of anemia after at least one year of GFD.

Description:

Celiac Disease (CD) is an autoimmune disease involving the mucosa of the small intestine, triggered by the ingestion of gluten in genetically predisposed individuals. CD represents a global health problem. The prevalence of CD, confirmed by intestinal biopsy, is estimated to be over 1% of the population of the Western world. Interestingly, the incidence of CD is continuously increasing around the world. CD is more common in women and children, although it is also becoming a common diagnosis also in men and adults. The clinical presentation of CD is characterized by a broad spectrum of both intestinal and extraintestinal manifestations, involving one or more organs. Several clinical categories of CD have been identified, including classical/typical CD (characterized by intestinal symptoms), atypical/subclinical CD (characterized by minor or extraintestinal symptoms), and silent CD (characterized by no symptoms). The category of "potential" CD was established for those patients with positive serology but without crypt hyperplasia and villous atrophy on duodenal biopsy. Duodenal biopsies can be avoided in the pediatric population, with high positive titer of IgA class anti-tTG (>10 times the upper limit of normal), associated with EMA-positivity. The treatment of CD is based on gluten-free diet (GFD).

Anemia is one of the most common extraintestinal clinical manifestations of CD, present in more than half of adult patients at the time of diagnosis. Anemia in CD has a multifactorial pathogenesis: a) lack of absorption (or, sometimes, loss, as in the case of iron), of some micronutrients, such as iron, folate, vitamin B12, copper and zinc, b) coexistence of a chronic inflammatory state, as in the case of inflammatory bowel disease (IBD), c) refractory CD, d) medullary aplasia.

The main purpose of this multicentre research is to evaluate, retrospectively, analyzing the clinical and laboratory data of CD patients, the presence, prevalence, severity, and morphological characteristics of anemia, trying to define, when possible, the underlying pathogenetic mechanisms, paying particular attention to the characteristics of menstrual cycles, the iron, folate and vitamin B12 metabolism, any chronic inflammatory state, and thyroid hormones. It will be also recorded, in a subgroup of the selected CD patients, any therapeutic responses (i.e., improvement/regression) of anemia after at least one year of GFD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: July 31, 2021
• Est. primary completion date: January 1, 2020
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

CD will be diagnosed according to the current guidelines. In details, the following standard criteria will be adopted to diagnose CD ("4 out of 5" rule):

• gluten/wheat-dependent symptoms, both intestinal and extraintestinal

• positivity of anti-deamidated gluten peptides (DPG) IgA and IgG antibodies, anti-transglutainase (tTG) IgA and IgG antibodies, and endomysium antibodies (EMA)

• presence of crypt hyperplasia and duodenal villous atrophy on duodenal biopsy

• presence of HLA haplotypes DQ2 and/or DQ8

• resolution of symptoms with a rigorous GFD

Additional inclusion criteria, both for the retrospective and prospective part of the study, will be:

• age >18 and <65 years

• complete clinical records

• clinical and laboratory follow-up of at least one year from diagnosis -

Exclusion Criteria:

• age <18 and >65 years

• incomplete medical records

• lack of clinical and laboratory follow-up of at least one year from diagnosis

• pregnancy

• alcohol and/or drug abuse

• diagnosis of IBD or other gastrointestinal organic disease

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Other:
• Presence, prevalence, severity, and morphological characteristics of anemia
Evaluation of the presence, prevalence, severity, and morphological characteristics of anemia, trying to define, when possible, the underlying pathogenetic mechanisms, paying particular attention to the characteristics of menstrual cycles, the iron, folate and vitamin B12 metabolism, any chronic inflammatory state, and thyroid hormones.
• Effect of gluten-free diet on anemia
Evaluation of the therapeutic responses (i.e., improvement/regression) of anemia after at least one year of GFD.

Locations

Country	Name	City	State
Italy	Department of Internal Medicine, University Hospital of Palermo	Palermo
Italy	Internal Medicine Division of the "Cervello-Villa Sofia" Hospital	Palermo	PA
Italy	Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca	Sciacca	Agrigento

Sponsors (1)

Lead Sponsor	Collaborator
University of Palermo

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Elli L, Norsa L, Zullo A, Carroccio A, Girelli C, Oliva S, Romano C, Leandro G, Bellini M, Marmo R, Soncini M, Monica F, De Francesco V, Paulon E, Cappellini MD, Motta I, Ferretti F, Orlando S, Mansueto P, Buscarini E, Manfredi G, Agostoni C, Tomba C, Can — View Citation

Martín-Masot R, Nestares MT, Diaz-Castro J, López-Aliaga I, Alférez MJM, Moreno-Fernandez J, Maldonado J. Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review. Nutrients. 2019 Oct 23;11(11). pii: E2557 — View Citation

Montoro-Huguet MA, Santolaria-Piedrafita S, Cañamares-Orbis P, García-Erce JA. Iron Deficiency in Celiac Disease: Prevalence, Health Impact, and Clinical Management. Nutrients. 2021 Sep 28;13(10). pii: 3437. doi: 10.3390/nu13103437. Review. — View Citation

Stefanelli G, Viscido A, Longo S, Magistroni M, Latella G. Persistent Iron Deficiency Anemia in Patients with Celiac Disease Despite a Gluten-Free Diet. Nutrients. 2020 Jul 22;12(8). pii: E2176. doi: 10.3390/nu12082176. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence, severity and morphologic characteristic of anemia	Blood count to evaluate red cell count and morphology	At baseline (=before diagnosis, on a gluten-containing diet) and at follow-up (=after at least one year of GFD)
Secondary	Pathogenic mechanisms of anemia	Evaluation of inadequate production or loss of erythrocytes a a result of bleeding or hemolysis	At baseline (=before diagnosis, on a gluten-containing diet) and at follow-up (=after at least one year of GFD)