Clinical trial NCT06124833: Integrated Gut Microbiome Data in Inflammatory Bowel Disease
Official title: Building an Integrated Gut Microbiome Data Analysis Platform and Conducting Comparative Clinical Studies in Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Inflammatory Bowel Diseases
Keywords: Inflammatory Bowel Diseases
Microbiota
Multiomics
Lead sponsor: Kyunghee University Medical Center
Sponsor class: OTHER
Collaborators: name: Kangbuk Samsung Hospital
name: Chung-Ang University Hosptial, Chung-Ang University College of Medicine
name: Inje University
name: Yeungnam University Hospital
name: Kyungpook National University Hospital
name: Chonnam National University Hospital
name: Wonkwang University Hospital
name: Daejeon St. Mary's hospital
name: Dankook University
name: Kyung Hee University Hospital at Gangdong
name: Inje University Ilsan Paik Hospital
name: Hanyang University
First posted: 2023-11-09
Enrollment: 900
Sex: ALL
Minimum age (years): 13
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Approximately 900 patients with inflammatory bowel disease (IBD) and about 200 first-degree relatives of the patients.

Brief summary: The inflammatory bowel disease (IBD) is a condition that afflects approximately 5 million people worldwide, with 1.4 million in the US and 2.2 million in Europe. By 2030, it is predicted that up to 1% of the entire Western population will have this disease. Notably, IBD encompasses conditions like Crohn's disease (CD) and Ulcerative colitis (UC). The emergence of this disease in non-Western countries is attributed to the rapid urbanization and industrialization which has led to the adoption of Westernized diets, an increase in the use of antibiotics early in life, and air pollution. These factors are suspected to induce changes in the gut microbiome, contributing to the rise of IBD. However, as an immune-mediated chronic intestinal disease, it is a multifactorial condition triggered by genetic mutations, gut microbial features, and environmental factors. Despite numerous studies, the exact causes remain insufficiently understood, emphasizing the importance of research and development to significantly benefit the health of the rapidly increasing patients. The study aims to construct a multi-omics analysis platform, including gut microbiome analysis, using biosamples collected from Korean patients with inflammatory bowel disease (IBD) and their families. Through this platform, comparative clinical research will be conducted to elucidate the pathophysiology of the disease and develop potential biomarkers.

Detailed description: This study aims to construct a multi-omics analysis platform using biosamples collected from patients with inflammatory bowel diseases (IBD) and their families. Through this platform, comparative clinical research will be performed to elucidate the pathophysiology of the disease and develop potential biomarkers. The specific research objectives are as follows:

1. To identify clinical risk factors, genotype-genome variations, microbiome, and metabolomic markers that can predict high-risk groups prone to poor therapeutic outcomes and complications.
2. To elucidate differences in genotype, gut microbiome distribution, and metabolomics between non-responders to biological agents and small molecule drugs versus those with good therapeutic responses. Using this information, the aim is to develop multi-omics biomarkers that can predict responders and non-responders.
3. To develop a multi-omics biomarker-based algorithm that can prioritize the choice of various biological agents or small molecule drugs for individual patients.
4. To construct guidelines for precision treatment by identifying multi-omics markers associated with the onset of IBD, disease exacerbation, and complications and by clarifying the role of multi-omics in the pathophysiological mechanism.
5. Using familial IBD patients and family control groups, the study aims to elucidate environmental and genetic factors associated with the onset of IBD.
6. By comparing with the data of healthy intestines (non-blood-related disease control group), the role of gut microbiota in the pathogenesis of IBD and associated diseases in Koreans will be clarified.
7. By comparing with data from other target disease patients (e.g., AS, HIV), the role of gut microbiota in the onset of immune-mediated inflammatory diseases and associated conditions will be elucidated.
8. An integrated analysis of prior genomic data, current project genomic data (from the gut, oral-respiratory, skin, urogenital tracts), other domestic and international cohorts, and overseas genomic data will clarify regional and ethnic differences and roles of gut microbiota in the pathogenesis of IBD and associated diseases in Koreans.
9. To elucidate the interrelationship between human host genetic traits, microbiome, and environmental influences in the pathogenesis of IBD.

Eligibility criteria: Inclusion Criteria:

1. Korean patients with inflammatory bowel disease (including Crohn's disease and ulcerative colitis) aged between 13 and 85 years (at the time of participant consent).
2. First-degree blood relatives of the patient, aged between 13 and 85, who have never been diagnosed with IBD and reside with the patient (Family Control Group).
3. Participants who have received a detailed explanation about this clinical trial, fully understand it, have voluntarily decided to participate, and have given written consent to comply with the precautions.

Exclusion Criteria:

* For IBD patients

  1. Indeterminate colitis.
* For family control group

  1. Individuals with a history of using medications listed in Appendix 13 (Family Control Group Medication History) within a pre-specified period before the microbiome collection date.
  2. Individuals who have been vaccinated within the last month (4 weeks) prior to the microbiome collection date.
  3. Individuals who have applied topical antibiotics or topical steroids to the face, scalp, neck, or arms, forearms, hands within 24 hours prior to the microbiome collection date.
  4. Individuals who have used vaginal/external genital medications, including antifungals, within 24 hours prior to the microbiome collection date.
  5. Individuals with acute conditions (e.g., moderate or severe diseases with or without fever; however, sample collection can be postponed until the participant recovers).
  6. Individuals with chronic and clinically significant histories of liver, digestive, cardiovascular, renal, neurological, respiratory, endocrine, immune, hematological disorders, malignancies, psychiatric conditions, or a history of drug abuse.
  7. Individuals who have drastically changed their diet for rapid weight gain or loss within 4 weeks prior to the microbiome collection date.
  8. Individuals with gastrointestinal disorders that could impact microbiome analysis and are not currently medically managed or individuals under treatment for the following conditions: Inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis), Irritable bowel syndrome (requiring drug therapy), Ulcers, acute or chronic pancreatitis, etc.
  9. Individuals requiring the use of incontinence diapers.
  10. Individuals with a positive urine pregnancy test, or who are pregnant or breastfeeding.
  11. Individuals suspected of having medical findings that may affect the sample collection at the time of microbiome sample collection.

Primary outcomes:
measure: Construction of a gut microbiome data platform by obtaining samples and clinical-related data from inflammatory bowel disease patients and control groups
timeFrame: 5 years
Secondary outcomes:
measure: Production and measurement of multi-omics data
timeFrame: 5 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Medical Center
Study officials:
affiliation: Kyunghee University Medical Center
name: Chang Kyun Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, Andrews E, Ajami NJ, Bonham KS, Brislawn CJ, Casero D, Courtney H, Gonzalez A, Graeber TG, Hall AB, Lake K, Landers CJ, Mallick H, Plichta DR, Prasad M, Rahnavard G, Sauk J, Shungin D, Vazquez-Baeza Y, White RA 3rd; IBDMDB Investigators; Braun J, Denson LA, Jansson JK, Knight R, Kugathasan S, McGovern DPB, Petrosino JF, Stappenbeck TS, Winter HS, Clish CB, Franzosa EA, Vlamakis H, Xavier RJ, Huttenhower C. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019 May;569(7758):655-662. doi: 10.1038/s41586-019-1237-9. Epub 2019 May 29.
citation: Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014 May;146(6):1489-99. doi: 10.1053/j.gastro.2014.02.009. Epub 2014 Feb 19.
citation: Integrative HMP (iHMP) Research Network Consortium. The Integrative Human Microbiome Project. Nature. 2019 May;569(7758):641-648. doi: 10.1038/s41586-019-1238-8. Epub 2019 May 29.