Cholesterol and CYP3A4/5 Metabolism Across Pregnancy and Postpartum

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

36 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-06-17

Study Completion Date

2023-06-30

Brief Summary

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This study addresses the second aim of the grant (R01 HD0899455), which is to determine temporal changes in CYP3A4-mediated drug metabolism sequentially across pregnancy and after birth.

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Detailed Description

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This study addresses the second aim of the grant (R01 HD0899455), which is to determine temporal changes in CYP3A4-mediated drug metabolism sequentially across pregnancy and after birth.

In studies with human hepatocytes, we found that serum from women in the first trimester led to the highest CYP3A4 expression compared to those from the second or third trimester or after birth. Among the hormones with elevated plasma concentrations in early pregnancy, our studies revealed that thyroid hormone enhances CYP3A4 expression in human hepatocytes. Based on the results, we hypothesized that CYP3A4-mediated drug metabolism is highest during early pregnancy (compared to the later time points of pregnancy or postpartum period) in part due to changes in thyroid hormone concentration.

To test this hypothesis, we will evaluate the conversion of endogenous cholesterol to its 4β-hydroxycholesterol metabolite, which is facilitated by CYP3A4. To assess additional factors that affect CYP3A activity, we will obtain DNA. About 75% of African Americans, but only 10-20% of people of European descent, carry the active allele CYP3A5\*1, which significantly increases the clearance of many CYP3A4/5 substrates, including the conversion of cholesterol to 4β-hydroxycholesterol.

Conditions

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Pregnancy Related

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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OPTIMOM residual samples

Residual plasma samples collected in one of our prior studies monthly across pregnancy (OPTIMOM, NICHD 1U54HD085601-01, Clinical Trials.gov ID NCT02519790; K. Wisner, PI) will be evaluated for cholesterol and 4β-hydroxycholesterol.

These samples were obtained from women who gave their consent for use of their blood samples for future studies. All OPTI-MOM participants have been genotyped for variants in CYP3A5 using commercial allelic discrimination assays (ThermoFisher Scientific, Waltham, MA, with Taqman probes.)

No interventions assigned to this group

Newly recruited subjects

Plasma samples will be collected from newly recruited subjects.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* English speaking
* Pregnant before 14w0d OR postpartum between before 18w0d
* Singleton gestation (as this will result in more consistent inter-individual measures)

Exclusion Criteria

* Chronic use of compounds that are substrates or inhibitors of CYP3A4 inhibitors, which will interfere with the concentrations and ratio. Potent inhibitors include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit. Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St. John's Wort and glucocorticoids.
* Diagnosis of alcoholism or substance use.
* Covid infection or within 4 weeks of positive test due to possible effect on hepatic function

Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes