Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05151913 |
| Other study ID # |
META001 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 14, 2017 |
| Est. completion date |
October 14, 2019 |
Study information
| Verified date |
November 2021 |
| Source |
MetaboGen AB |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This is an exploratory non-therapeutic study to study the microbiome patterns during
pregnancy in women with ICP in order to identify specific bacterial strains for further
product development.
Description:
Intrahepatic Cholestasis in Pregnancy (ICP) is a disease that appears in the later stage of
pregnancy with itching (pruritus) and increased risk of fetal complications. It is the most
prevalent pregnancy-specific liver disease, affecting between 1 and 20 % of all pregnant
women, depending on ethnicity and geographic location.
The condition is associated with an increased risk of adverse fetal outcomes, including
preterm labour and intrauterine death. Further, ICP is associated with an increased risk for
pre-eclampsia, thyroid disease, diabetes and cancer. ICP is typically present during the
third trimester, when the serum concentrations of progesterone and estrogens reach their
peak, and also, the time when the gut barrier has an increased permeability. In ICP subjects,
both altered progesterone and bile acid metabolism is observed.
The underlying etiology for ICP is unknown, but there are indications that the gut microbiota
may be involved. It has become increasingly clear that the gut microbiota is associated with
metabolic diseases and has an important function in metabolizing endogenous and dietary
metabolites. Bile acids are metabolized by the gut microbiota by deconjugation and production
of secondary metabolites, ursodeoxycholic acid (UDCA) being one example of a secondary bile
acid produced by the microbiota. Bile acids are produced from cholesterol by a series of
hepatic enzymes generating cholic acid (CA) and chenodeoxycholic acid (CDCA) in humans that
are conjugated to predominantly glycine. These primary bile acids are stored in the gall
bladder from where they are released upon a meal. The majority of conjugated bile acids are
reabsorbed from the ileum, but through the action of microbial bile salt hydrolase (BSH), the
bile acids escape reabsorption and enter the colon where they can be further metabolized.
Accordingly, bile acid deconjugation reduces enterohepatic recirculation of bile acids and
thereby reduces the total bile acid pool. Reduction of bile acid levels are crucial to reduce
pruritus and reduce fetal complication risks in ICP.
The aim is to identify biomarkers in the microbiota associated with ICP and the onset of this
disease, or state of the disease, during pregnancy. Bacterial species that have a capability
for UDCA production and correlate with sulphated progesterone metabolites are of specific
interest. Furthermore, bacteria with sulphating and desulphating capabilities are also of
interest.
