Histomolecular Profiling in Small-Bowel Diseases

NCT07556328 | Recruiting

• 1 other identifier: R25009
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 3

Brief Summary

This prospective cohort study aims to establish reliable histological reference values for normal small-bowel mucosa, improve histological diagnostic quality in celiac disease, and develop an advanced molecular profile for disease diagnosis and treatment response evaluation. The study will collect duodenal biopsies from three groups: healthy controls undergoing clinically indicated gastroscopy, patients referred for primary celiac disease diagnostics, and patients with small-bowel mucosal injury unresponsive to a gluten-free diet. Patients will undergo routine clinical assessment via standard pathology review of diagnostic biopsies. Biopsies will be analyzed using digital morphometry, AI-based image analysis, RNA sequencing (transcriptomics), and intestinal organoid cultures.

Conditions

Celiac Disease; Refractory Celiac Disease; Small Bowel Disease

Keywords

celiac disease; duodenal biopsy; histology; digital morphometry; artificial intelligence; RNA sequencing; transcriptomics; organoids; small bowel; villous atrophy; molecular profiling; machine learning

Outcome Measures

Primary Outcomes (2)

• Villus-to-crypt ratio

  Villus-to-crypt ratio in normal duodenal mucosa established by digital morphometry

  Research biopsy obtained at time of endoscopy; digital morphometry performed through study completion (up to December 31, 2025)

• Transcriptomic

  Transcriptomic (RNA-Seq) profile of duodenal mucosa in celiac disease patients and healthy controls

  Research biopsy obtained at time of endoscopy; RNA-Seq analysis performed through study completion (up to December 31, 2025)

Secondary Outcomes (3)

• AI/machine-learning-based image analysis

  Throughout study period up to December 31, 2035

• Organoid culture models of celiac

  Throughout study period up to December 31, 2035

• Comparison of transcriptomic profiles

  Throughout study period up to December 31, 2035

Study Arms (3)

Group 1 - Healthy Controls (n = 130)

Adults ≥18 years undergoing clinically indicated gastroscopy (e.g., reflux symptoms) with no suspicion of celiac disease and negative celiac antibodies (anti-transglutaminase and/or anti-endomysium).

Group 2 - Celiac Disease Diagnostic Group (n = 130)

Adults referred for primary celiac disease diagnostics requiring duodenal biopsy, in accordance with standard care guidelines.

Group 3 - Refractory Small-Bowel Injury Group (n = 40)

Adults with small-bowel mucosal injury (villous atrophy) that does not respond to a gluten-free diet, referred for endoscopy to exclude ongoing histological damage.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy, seropositive patients and refractory to treatment

You may qualify if:

• Age ≥ 18 years
• Clinically indicated upper gastrointestinal endoscopy (gastroscopy)
• Written informed consent obtained prior to procedure
• For Group 1 (Healthy Controls): Negative celiac disease antibodies (anti-transglutaminase and/or anti-endomysium); no suspected celiac
• For Group 2 (Celiac Diagnostics): Referred for primary celiac disease diagnostics requiring duodenal biopsy
• For Group 3 (Refractory Injury): Confirmed small-bowel mucosal injury not responsive to a gluten-free diet

You may not qualify if:

• For Group 1 (Healthy Controls): Other small-bowel diseases causing mucosal injury, including Crohn's disease and small-bowel ulcers
• Inability to provide written informed consent
• Refusal to participate

Sponsors & Collaborators

• Tampere University Hospital: lead
• Tampere University: collaborator

Study Sites (3)

Hatanpää Specialist Medical Care

Tampere, 33720, Finland

RECRUITING

Tampere University Hospital (Tays)

Tampere, 33720, Finland

RECRUITING

Valkeakoski Regional Hospital

Valkeakoski, 33720, Finland

RECRUITING

Related Publications (5)

• Schuppan D, Maki M, Lundin KEA, Isola J, Friesing-Sosnik T, Taavela J, Popp A, Koskenpato J, Langhorst J, Hovde O, Lahdeaho ML, Fusco S, Schumann M, Torok HP, Kupcinskas J, Zopf Y, Lohse AW, Scheinin M, Kull K, Biedermann L, Byrnes V, Stallmach A, Jahnsen J, Zeitz J, Mohrbacher R, Greinwald R; CEC-3 Trial Group. A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease. N Engl J Med. 2021 Jul 1;385(1):35-45. doi: 10.1056/NEJMoa2032441.

  PMID: 34192430 BACKGROUND

• Taavela J, Viiri K, Popp A, Oittinen M, Dotsenko V, Peraaho M, Staff S, Sarin J, Leon F, Maki M, Isola J. Histological, immunohistochemical and mRNA gene expression responses in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded duodenal biopsies. BMC Gastroenterol. 2019 Nov 15;19(1):189. doi: 10.1186/s12876-019-1089-7.

  PMID: 31730447 BACKGROUND

• Taavela J, Viiri K, Valimaki A, Sarin J, Salonoja K, Maki M, Isola J. Apolipoprotein A4 Defines the Villus-Crypt Border in Duodenal Specimens for Celiac Disease Morphometry. Front Immunol. 2021 Jul 29;12:713854. doi: 10.3389/fimmu.2021.713854. eCollection 2021.

  PMID: 34394117 BACKGROUND

• Risnes LF, Reims HM, Doyle RM, Qiao SW, Sollid LM, Lundin KEA, Christophersen A. Gluten-Free Diet Induces Rapid Changes in Phenotype and Survival Properties of Gluten-Specific T Cells in Celiac Disease. Gastroenterology. 2024 Jul;167(2):250-263. doi: 10.1053/j.gastro.2024.03.027. Epub 2024 Mar 28.

  PMID: 38552723 BACKGROUND

• Dotsenko V, Oittinen M, Taavela J, Popp A, Peraaho M, Staff S, Sarin J, Leon F, Isola J, Maki M, Viiri K. Genome-Wide Transcriptomic Analysis of Intestinal Mucosa in Celiac Disease Patients on a Gluten-Free Diet and Postgluten Challenge. Cell Mol Gastroenterol Hepatol. 2021;11(1):13-32. doi: 10.1016/j.jcmgh.2020.07.010. Epub 2020 Jul 31.

  PMID: 32745639 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Duodenal mucosal biopsies (formalin-fixed paraffin-embedded blocks for histology; fresh biopsies in RNAlater for RNA-Seq; biopsies in Cell Recovery freezing medium for organoid cultures). Optional: DNA from RNA samples or organoid cultures.

MeSH Terms

Conditions

Celiac Disease

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Juha Taavela

CONTACT

+358443400330; juha.taavela@tuni.fi

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD,

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: April 29, 2026
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2035
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FI (3)