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

NCT06500754 | Recruiting

• 1 other identifier: P/21-098
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Celiac Disease; Villous Atrophy of Intestine

Keywords

persistent villous atrophy; ultra-strict gluten-free diet; microbiota; epigenetics

Outcome Measures

Primary Outcomes (1)

• Persistent villous atrophy frequency

  proportion of patients showing villous atrophy after 2 years of an intentionally strict gluten-free diet

  at inclusion

Study Arms (1)

Celiac Disease patients

Other: Ultra-strict gluten-free diet

Interventions

Ultra-strict gluten-free diet OTHER

ultra-strict gluten-free diet (avoiding traces and contamination) under dietitian supervision

Celiac Disease patients

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Celiac Disease patients from the participating hospitals

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Mutua de Terrassa: lead

Study Sites (1)

Hospital Universitari MútuaTerrassa

Terrassa, Barcelona, 08221, Spain

RECRUITING

Related Publications (20)

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Biospecimen

Retention: SAMPLES WITH DNA

duodenal biopsy samples, blood, urine and feces

MeSH Terms

Conditions

Celiac Disease

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 15, 2024
• Study Start: January 1, 2022
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 19, 2024

Record last verified: 2024-07

Locations

ES (1)