SSAT 054: Non Genetic Factors in the Pathogenesis of IBD in Twins

Non Genetic Factors in the Pathogenesis of Inflammatory Bowel Disease in Twins

This study aims to investigate the role of non-genetic factors in the pathogenesis of inflammatory bowel disease.An exploratory study to investigate differences between the epigenome, microbiota and functional immunology in twins discordant for inflammatory bowel disease.

Study Overview

• Status: Unknown
• Conditions: Crohn's Disease; Ulcerative Colitis; Inflammatory Bowel Disease

Detailed Description

Background: The inflammatory bowel diseases (IBD), Crohn's Disease (CD) and Ulcerative Colitis (UC), are debilitating conditions with a complex aetiology. The biggest risk factor for developing IBD is having an affected first degree relative. However when an identical twin is diagnosed with IBD, the other twin goes on to develop the condition in only 20-55% of cases.

Recent research suggests the microbiota the ecosystem of bacteria within the gut may trigger disease in susceptible individuals. Another important research area is the epigenome changes to the structure and regulation of our genome which occur throughout our life. It is known that siblings of Crohn's Disease sufferers have a changes to the immune system characteristic of Crohn';s. However it is not known whether these changes are due to genetic similarity or shared environment. Comparison between mono and dizygotic twins elucidates the relative importance of genetic and environmental factors.

Primary Objective: An exploratory study to investigate differences between the epigenome, microbiota and functional immunology in twins discordant for inflammatory bowel disease.

Study Design: Multicentre basic science study involving human participants

Planned sample size: 200 data subjects (100 twin pairs)

Methodology:

A) Identification of twin pairs where one or both have inflammatory bowel disease via:

1. IBD Nixon Twin and Multiplex Registry.
2. Advertising for twin pairs via BSG website and newsletters/patient support groups/social media sites/clinic posters.
3. Identification by study sites B) Obtaining formal written consent C) Collection of blood, stool and urine.

D) The following analysis will be carried out:

• Epigenetics (blood) DNA extraction and subsequent methylation analysis and bisulphate conversion with 450 Illumina beadchip assay
• Functional immunology (blood) - flow cytometry of CD3, CD4 and CD8 cells. (London Twin pairs discordant for Crohn's Disease)
• 16S rRNA gene sequencing (stool) - of bacterial DNA
• Metabolomic profiling (Urine and stool) - using Nuclear Magnetic Resonance (NMR) and mass spectrometry E) Collection of dietary history information for the previous 72hr period Study Duration: 2 years (single visit).

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SWIO 9NH
    • Chelsea and Westminster Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

200

Description

Inclusion Criteria:

• Monozygotic twins discordant for IBD
• Monozygotic twins concordant for IBD
• Dizygotic twins discordant for IBD
• Dizygotic twins concordant for IBD
• Healthy controls

Exclusion Criteria:

• <18 years old
• Antibiotics within past 3 months of sample collection
• Unable to give informed consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in DNA methylation patterns between twin pairs	1 day (1 visit only)
Difference in microbiota composition and metabolomic profiles between IBD phenotypes	1 day (1 visit only)
Comparison of microbiota composition and metabolic profiles with DNA methylation patterns	1 day (1 visit only)
Difference in T cell phenotypes and antigen presenting cells between twin pairs discordant for IBD	1 day (1 visit only)

Collaborators and Investigators

• Sponsor: St Stephens Aids Trust
• Investigators: Principal Investigator: Marcus Harbord, MD, Chelsea And Westminster Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): October 1, 2017

Study Registration Dates

• First Submitted: January 7, 2015
• First Submitted That Met QC Criteria: March 9, 2015
• First Posted (Estimate): March 10, 2015

Study Record Updates

• Last Update Posted (Actual): October 26, 2017
• Last Update Submitted That Met QC Criteria: October 25, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: IBD; CD; twins; UC
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases
• Other Study ID Numbers: SSAT 054