Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03462875 |
| Other study ID # |
ENIGMA II |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 29, 2018 |
| Est. completion date |
February 28, 2024 |
Study information
| Verified date |
February 2023 |
| Source |
Chinese University of Hong Kong |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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 characterized and studied in detail. Microbial findings will be related to
a detailed assessment of environmental factors that permit microbial changes or expression.
Description:
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 have 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, The investigators 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 were
decreased in abundance in active CD, in patients at the 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 the characteristics of these two bacterial families, the microbial environment
interfacing with these organisms is 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 a detailed examination of
environmental risk factors for the development of CD, in the same patients.
