Clinical trial NCT05151913: The Microbiome Composition in Women With Recurring Intrahepatic Cholestasis of Pregnancy (ICP)
Official title: Exploratory, Prospective, Non-therapeutic, Paired- Matched Controlled Two-arm Study to Investigate the Microbiome Composition in Women With Recurring Intrahepatic Cholestasis of Pregnancy (ICP)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Intrahepatic Cholestasis of Pregnancy
Keywords: Pregnancy
Microbiome
Lead sponsor: MetaboGen AB
Sponsor class: INDUSTRY
Collaborators: name: Skane University Hospital
name: Stockholm South General Hospital
First posted: 2021-12-09
Enrollment: 105
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women with previously completed parturition with intrahepatic cholestasis of pregnancy and matched controls

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

Arm 1

* Pregnant woman \> 18 years
* Signed informed consent for participation
* At least one previously completed parturition with ICP
* Willingness and ability to comply with the study procedures, visit schedules and other instructions regarding the study

Arm 2

* Pregnant woman ≥ 18 years (±5 calendar years from the matched subject in arm 1)
* Signed informed consent for participation
* At least one previously completed parturition
* No previous ICP
* Willingness and ability to comply with the study procedures, visit schedules and other instructions regarding the study

Exclusion Criteria:

* Multifetal pregnancy (twins, triplets etc.)
* Latin American ethnicity
* Use of any systemic antibiotics within 3 months prior to enrollment
* Medical history of liver disease (other than previous ICP for subjects in arm 1)
* Medically significant gastrointestinal disorder which, in the opinion of the investigator, may affect the results or the subject ́s ability to comply with the study
* History or concurrent status of any clinically significant disease or disorder which, in the opinion of the investigator, may influence the results or the subject ́s ability to participate in the study
* Participation in any other clinical study that included drug treatment within 3 months prior to enrollment
* Serious bacterial or chronic viral infection such as human immunodeficiency virus (HIV) or hepatitis virus at enrollment visit
* Any other condition which, in the Investigator ́s opinion, makes the subject unsuitable for study participation

Primary outcomes:
measure: Gut microbiome composition
timeFrame: Pregnancy week 9+0 - 19+6 until 6 weeks post-partum (+ 2 weeks)
Secondary outcomes:
measure: Bile acids levels
timeFrame: Pregnancy week 9+0 - 19+6 until 6 weeks post-partum (+ 2 weeks)
measure: Liver function test AST
timeFrame: Pregnancy week 9+0 - 19+6 until 6 weeks post-partum (+ 2 weeks)
measure: Liver function test ALT
timeFrame: Pregnancy week 9+0 - 19+6 until 6 weeks post-partum (+ 2 weeks)
measure: Liver function test GGT
timeFrame: Pregnancy week 9+0 - 19+6 until 6 weeks post-partum (+ 2 weeks)
measure: Liver function test bilirubin
timeFrame: Pregnancy week 9+0 - 19+6 until 6 weeks post-partum (+ 2 weeks)
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skane University Hospotal
city: Stockholm
country: Sweden
facility: Stockholm South General Hospital
Study officials:
affiliation: Skane University Hospital, Sweden
name: Helena Strevens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: