Mapping the Human Colon Using Single Cell Sequencing

NCT05195502 | Unknown DMC

• 1 other identifier: COLKEND01
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The overall purpose of this study is to describe the cellular composition of the human colon and its gene expression using scRNAseq and scATACseq methods. This will potentially provide is with a detailed map of the colon aiding our understanding of how diseases of the colon develop as well as the colons influence on systemic diseases such as type II diabetes.

Conditions

Diabetes; Large Bowel Cancer; Inflammatory Bowel Diseases

Outcome Measures

Primary Outcomes (2)

• Profiling of open chromatin regions

  Mapping of cell types, including rare cell types, using profiling of open chromatin regions. (ATAC-seq) in mucosal biopsies from the large bowel

  2 years

• Evaluation of metabolic profile

  Using bioimpedance, insulin and glucose measurements and CHiP-seq we will determine patient phenotype and epigenetics to evaluate their metabolic risk-profile and correlate this to cell types in the large bowel

  2 years

Secondary Outcomes (1)

• Colonic biofilm

  2 years

Study Arms (1)

Screening colonoscopy patients

Patients referred for out-patient colonoscopy in the Danish Colorectal Screening program

Diagnostic Test: Biopsy

Interventions

Biopsy DIAGNOSTIC_TEST

Participants included in the study, will have additional biopsies performed during their colonoscopy

Screening colonoscopy patients

Eligibility Criteria

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

Study Population

Citizens aged 50 to 74 are invited to partake in screening for bowel cancer every second year. Patients who accept referral based on a positive fecal immunochemical test, will be invited to participate in this study

You may qualify if:

• Patients referred for out-patient colonoscopy as a result of positive hemoccult.
• Patients able to read and understand danish.
• Patients able to give informed consent.
• Patients of Scandinavian ethnicity.

You may not qualify if:

• Previous large bowel resections
• Suspicion pre or intraoperatively of benign or malignant disease of the colon
• Known inflammatory bowel disease.
• Immuno-modulation treatment
• Chemotherapy.
• Daily smoking
• \> 21 weekly units of alcohol
• \< 18 years of age

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• The Novo Nordisk Foundation Center for Basic Metabolic Research: collaborator

Study Sites (1)

Bispebjerg University Hospital

Copenhagen, 2720, Denmark

Location

Related Publications (5)

• Kaz AM, Wong CJ, Dzieciatkowski S, Luo Y, Schoen RE, Grady WM. Patterns of DNA methylation in the normal colon vary by anatomical location, gender, and age. Epigenetics. 2014 Apr;9(4):492-502. doi: 10.4161/epi.27650. Epub 2014 Jan 10.

  PMID: 24413027 BACKGROUND

• Knight JM, Kim E, Ivanov I, Davidson LA, Goldsby JS, Hullar MA, Randolph TW, Kaz AM, Levy L, Lampe JW, Chapkin RS. Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue. Physiol Genomics. 2016 Sep 1;48(9):651-9. doi: 10.1152/physiolgenomics.00023.2016. Epub 2016 Jul 8.

  PMID: 27401218 BACKGROUND

• Forgue-Lafitte ME, Fabiani B, Levy PP, Maurin N, Flejou JF, Bara J. Abnormal expression of M1/MUC5AC mucin in distal colon of patients with diverticulitis, ulcerative colitis and cancer. Int J Cancer. 2007 Oct 1;121(7):1543-9. doi: 10.1002/ijc.22865.

  PMID: 17565737 BACKGROUND

• Costales-Carrera A, Fernandez-Barral A, Bustamante-Madrid P, Dominguez O, Guerra-Pastrian L, Cantero R, Del Peso L, Burgos A, Barbachano A, Munoz A. Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue. Cancers (Basel). 2020 Aug 15;12(8):2302. doi: 10.3390/cancers12082302.

  PMID: 32824266 BACKGROUND

• Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide. Curr Protoc Mol Biol. 2015 Jan 5;109:21.29.1-21.29.9. doi: 10.1002/0471142727.mb2129s109.

  PMID: 25559105 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

1. Bloodsamples, including full blood, serum and plasma 2. Endoscopic mucosal biopsies from the large bowel

MeSH Terms

Conditions

Diabetes Mellitus; Colonic Neoplasms; Inflammatory Bowel Diseases

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Gastroenteritis

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jacob Antonsen, MD

  Bispebjerg Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Registrar

Study Record Dates

• First Submitted: January 7, 2022
• First Posted: January 19, 2022
• Study Start: July 1, 2022
• Primary Completion: December 31, 2022
• Study Completion: July 1, 2024
• Last Updated: February 8, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)