Histomolecular Profiling in Small-Bowel Diseases

Официальное название

Histological and Molecular Profiling in the Diagnostics and Treatment of Small-Bowel Diseases - A Prospective Cohort Study (The DeepBowel Study)

Обзор

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.

Подробное описание

Celiac disease is a chronic autoimmune condition affecting approximately 2.4% of the Finnish population. Despite advances in diagnostics, histological assessment of duodenal biopsies remains the gold standard for diagnosis in most cases. However, histological evaluation is subject to inter-observer variability, with a 10% diagnostic error rate reported in international multicenter studies.

This study will:

1. Establish reliable digital morphometric reference values (villus-to-crypt ratio) for normal small-bowel mucosa using digitized biopsy slides and AI/machine-learning-based analysis tools; 2. Investigate molecular pathways underlying celiac disease progression and treatment response through RNA sequencing (RNA-Seq transcriptomics) of biopsies from celiac disease patients and healthy controls, with a reference comparison to a drug-trial dataset; 3. Model disease progression and refractory small-bowel injury using intestinal organoid cultures derived from biopsies of celiac patients, refractory patients, and healthy controls.

Research biopsy samples will be processed at the Tampere University Celiac Disease Research Center under pseudonymization. Statistical analyses will be done in collaboration with the study statistician. All data will be stored for 15 years following study completion.

Первичные конечные точки

• Villus-to-crypt ratio [Срок оценки: Research biopsy obtained at time of endoscopy; digital morphometry performed through study completion (up to December 31, 2025)]
• Transcriptomic [Срок оценки: Research biopsy obtained at time of endoscopy; RNA-Seq analysis performed through study completion (up to December 31, 2025)]

Вторичные конечные точки (3)

• AI/machine-learning-based image analysis [Срок оценки: Throughout study period up to December 31, 2035]
• Organoid culture models of celiac [Срок оценки: Throughout study period up to December 31, 2035]
• Comparison of transcriptomic profiles [Срок оценки: Throughout study period up to December 31, 2035]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Финляндия · 3 центра

• Hatanpää Specialist Medical Care — Tampere
• Tampere University Hospital (Tays) — Tampere
• Valkeakoski Regional Hospital — Valkeakoski

Публикации

• 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. PMID 34192430
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07556328 · R25009

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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