Persistent Villous Atrophy in Celiac Disease Patients Following an Intentionally Strict Gluten-free Diet (CADER2)

July 18, 2024 updated by: Hospital Mutua de Terrassa

Study of the Causes and Consequences of Persistent Villous Atrophy Despite an Intentionally Strict Gluten-free Diet in Celiac Disease Patients - Effect of an Ultra-strict Gluten-free Diet on Persistent Villous Atrophy

Celiac disease (CD) is an immune-mediated disease characterized by small intestinal inflammation from gluten ingestion, a group of proteins present in various cereals, including wheat, rye, barley, spelt, and kamut. CD is the most common chronic gastrointestinal disease and one of the most common autoimmune disorders, estimated to affect 0.4-1.7% of the general population. Currently, a strict lifelong gluten-free diet (GFD) is the only available treatment to avoid the inappropriate inflammatory response and prevent the shortening of the villi lining the small intestine (villous atrophy). However, a significant proportion of CD patients, ranging from 4% to 79%, show persistent villous atrophy despite following an intentional GFD. The causative factors and the clinical consequences of persistent villous atrophy in CD patients are not well known yet but might resemble untreated CD long-term complications.

Interestingly, in the precedent study (CADER) persistent villous atrophy was found to be more present in patients diagnosed at an older age (65% of CD patients diagnosed after 30 years of age) than in younger patients. Moreover, unintentional exposure to gluten was found in 70% of the cases. The causative factors of this hypersensitivity to small amounts of gluten present in older patients are unknown. The intestinal microbiota and age-related epigenetic changes may help maintaining the dysregulation of the immune response, causing older patients to be hypersensitive to small amounts of gluten.

The aim of this study (CADER2) is to identify the immunological and clinical consequences of persistent villous atrophy in CD and study whether changes in the intestinal microbiome and age-related epigenetic modifications may contribute to it. Last, the investigators want to assess if an ultra-strict GFD can be a viable and effective alternative to treat this subset of CD patients. In order to achieve these objectives, the study includes 2 phases: 1) Cross-sectional study to assess the causes and the clinical consequences of persistent villous atrophy in CD patients; and 2) Longitudinal study to evaluate the potential therapeutic effect of an ultra-strict GFD on persistent villous atrophy and its subtle clinical manifestations.

The investigators hypothesize that persistent villous atrophy in CD patients despite an intentional GFD is associated with chronic low-grade inflammation and increased circulating cytokines in blood, potentially leading to cognitive deficits, fatigue, anxiety, depression, malnutrition, sarcopenia and osteoporosis. The intestinal microbiota and age-related epigenetic changes may help to maintain the dysregulation of the immune response, causing patients to be hypersensitive to small amounts of gluten. This subset of CD patient could highly benefit from an ultra-strict GFD.

To date, six centers have been recruited: Hospital Universitari Mutua Terrassa (Barcelona), Hospital Clínico San Carlos (Madrid), Hospital Fundación Jiménez Díaz (Madrid), Hospital Universitario de La Princesa (Madrid), Hospital Universitario Ramón y Cajal (Madrid) and Hospital Universitario Virgen Macarena (Sevilla). Digestive, endocrine, nutritional and clinical psychology experts will be involved in the monitoring of the patients. Microbiome analysis will be performed at the Genomics Unit, Microbiota Laboratory (LABMIC) of the IdISSC (Madrid). The methylation studies (age-related epigenetic modifications) will be hired externally.

Overall, the results of this study (CADER2) may help identify new therapeutic strategies as well as improve the management of chronicity and care of CD patients who do not respond to the current treatment. Furthermore, it will contribute to a deeper understanding of the pathophysiological relationships between diet, microbiome, genetics and immunology in CD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • Terrassa, Barcelona, Spain, 08221
        • Recruiting
        • Hospital Universitari MutuaTerrassa
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Celiac Disease patients from the participating hospitals

Description

Inclusion Criteria:

  • Age at diagnosis 18 years or more.
  • Diagnosis of CD with villous atrophy, positive serology and clinical and serological response to GFD.
  • To be in a GFD for at least 2 years, with good adherence to it.
  • Negative or positive anti-transglutaminase (tTG2) IgA antibodies at low titers (<2 times the normal value) at recruitment.
  • Written informed consent.

Exclusion Criteria:

  • Refractory CD (RCD) type 2 and type 1
  • Other associated intestinal diseases (inflammatory bowel disease, microscopic colitis, other types of enteropathies).
  • Need for treatment with corticosteroids or immunosuppressants.
  • Surgeries or other diseases predisposing to bacterial overgrowth in the small intestine.
  • Pregnancy, lactation.
  • Associated chronic diseases (lung, heart, kidney, liver cirrhosis).
  • Alcoholism or drug addiction.
  • Schizophrenia-type psychiatric diseases, other psychoses, bipolar.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Celiac Disease patients
Other: Ultra-strict gluten-free diet
ultra-strict gluten-free diet (avoiding traces and contamination) under dietitian supervision

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Persistent villous atrophy frequency
Time Frame: at inclusion
proportion of patients showing villous atrophy after 2 years of an intentionally strict gluten-free diet
at inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Mutua de Terrassa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2022

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

July 8, 2024

First Submitted That Met QC Criteria

July 8, 2024

First Posted (Actual)

July 15, 2024

Study Record Updates

Last Update Posted (Actual)

July 19, 2024

Last Update Submitted That Met QC Criteria

July 18, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P/21-098

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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