The ENIGMA Study: Eastern Inflammatory Bowel Disease Gut Microbiota

Study Purpose

The incidence of inflammatory bowel diseases, (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), is increasing in the developing world. Our recent Asia-Pacific population-based study in 8 Asian countries and Australia has demonstrated that Hong Kong and China have amongst the highest disease incidences in Asia while Australia has the equal highest incidence of these diseases in the world. The ENIGMA project comprises three main enteric microbiome domains of central importance to Crohn's disease. Two specific organisms which may play a critical role in disease pathogenesis, including the candidate protective bacterium, and the novel pathogenic candidate, will be characterised and studied in detail. Microbial findings will be related to detailed assessment of environmental factors that permit microbial changes or expression.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. aged ≥18 years old 2. competent to provide informed consent (no mental illness or dementia, etc. that will hinder the understanding) 3. living in the same area for recent 6 months

Exclusion Criteria:

1. Use of anticoagulants within 1 week 2. Use of prebiotics, probiotics or antibiotics in recent 3 months 3. Use of laxatives or "Stoppers" in the last 3 months 4. Vaccination within 3 months 5. Recent dietary changes (e.g. becoming vegetarian/vegan) 6. Known complex infections or sepsis (excl. simple infections such as influenza etc.) 7. Known history or concomitant significant food allergies 8. Known history of severe organ failure (including decompensated cirrhosis, malignant disease, kidney failure, epilepsy, active serious infection, acquired immunodeficiency syndrome) 9. Bowel surgery in the last 6 months (excluding colonoscopy/ procedure related to perianal disease) 10. Having stoma 11. Known pregnancy 12. Travel history within 4 weeks (need to define the travel history in China) 13. Known contraindications to colonoscopy 14. Colonoscopy in the last month prior to sampling

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03462875
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Chinese University of Hong Kong
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Siew Chien Ng, PhD
Principal Investigator Affiliation Chinese University of Hong Kong
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOtherOtherOtherOtherOtherOther
Overall Status Not yet recruiting
Countries Hong Kong
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Crohn's Disease, Microbiota, Dietary Pattern, Environmental Factors
Additional Details

The incidence of inflammatory bowel diseases, (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), is increasing in the developing world. Our recent Asia-Pacific population-based study in 8 Asian countries and Australia has demonstrated that Hong Kong and China have amongst the highest disease incidences in Asia while Australia has the equal highest incidence of these diseases in the world. The incidence of IBD in Hong Kong and China has risen three-fold in the past decade. Asian populations have genetic predispositions to develop IBD which are different to the West, but these genetic abnormalities are not obligatory for the development of IBD, with environmental factors playing a much more important pathogenic role. These factors include travel with exposure to a new population in childhood, diet, antibiotic use during childhood, socioeconomic status, and a rural versus urban upbringing, each of which alone, or in combination, are likely to affect the microbiome. Compelling evidence suggests that gut microbes play a critical role in disease pathogenesis, while geographic, dietary and ethnic factors impact the microbial composition. In addition to broad changes in the microbial profile in IBD, a number of specific changes have been identified, such as a decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium Prausnitzii. Although the commensal gut microbiota is ecologically and functionally perturbed in IBD, there is unexplained heterogeneity among IBD subtypes and individual patients. In new-onset treatment naïve patients with CD, enrichment for the Enterobacteriaceae and depletion of Clades IV and XIVa Clostridia during disease-associated inflammation have been reported. Metagenomic studies and microarray analyses in Western populations and limited Asian data have demonstrated a reduction of Firmicutes, such as F. prausnitzii in Crohn's disease (CD), and an increased in Escherichia coli and Fusobacterium. It is unknown if the changes in putative pathogens and/or protective organisms identified in Western populations, such as E. coli and F. prausnitzii, respectively, are present in IBD patients in Asia. Information is also lacking about the degree of genetic variation between the bacteria assigned to these taxonomic groups from different ethnic and geographical regions. Most of the published work on these bacteria, and their potential pathogenic or protective role in CD, has been undertaken with isolates recovered from European and North American subjects. For these reasons, we believe there is a need to firmly establish whether the microbial changes outlined above are also encountered in patients from other parts of the world, including Asian countries with high disease incidence and increasing disease incidence. The Post-Operative Crohn's Endoscopic Recurrence (POCER) study was undertaken in 17 hospitals around Australia and New Zealand, and recruited 174 patients who were then monitored for 18 months post-operatively. The microbiota analyses undertaken on a subset of the POCER study patient cohort showed that F. prausnitzii, previously identified as being capable of producing anti-inflammatory properties possible key organism in preventing active CD was decreased in abundance in active CD, in patients at surgery who subsequently recurred, and in patients at the time of recurrence. Most of the published studies examining the anti-inflammatory properties of F. prausnitzii have been undertaken with a single strain of European origin. Despite the promise associated with the anti-inflammatory properties produced by F. prausnitzii it remains to be determined whether this bacterium is protective against inflammation, or diminishes subsequent to the onset of inflammation. In summary, it is currently unclear if the changes in putative pathogens and protective organisms present in Western IBD populations are consistently observed with CD patients in Asia. Nor is it known whether the functional capabilities of these bacteria differ across ethnic and/or geographic regions. In addition to characteristics of these two bacterial families, the microbial environment interfacing with these organisms are likely to play a critical role in their expression and function. This will be examined in detail using broad sequencing techniques. Microbial analyses will be undertaken in the context of detailed examination of environmental risk factors for the development of CD, in the same patients.

Arms & Interventions

Arms

: Crohn's Disease Patients

Subjects having confirmed diagnosis of Crohn's disease which is defined by endoscopy, radiology and histology; and having documented ileocaecal or right-sided colonic disease

: Non-household Controls

Non-affected subjects who will under colonoscopy for polyp or colorectal cancer screening, or investigations of gastrointestinal symptoms other than Inflammatory Bowel Disease

: First Degree Relatives

Non-affected first degree relatives of cases

: Household/co-habitant Controls

Non-affected subjects living in the same household with the cases in the recent 6 months

Interventions

Contact a Trial Team

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International Sites

Prince of Wales Hospital, Hong Kong, Hong Kong

Status

Address

Prince of Wales Hospital

Hong Kong, ,

Site Contact

Siew Chien Ng, PhD

siewchienng@cuhk.edu.hk

35053996

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