Cholesterol and CYP3A4/5 Metabolism Across Pregnancy and Postpartum (CAMCAP)

April 22, 2024 updated by: Northwestern University
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.

Study Overview

Status

Completed

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

36

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Asher Center for the Study and Treatment of Depressive Disorders

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Community sample of pregnant or postpartum woman in areas surrounding Chicago, IL.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.)
Newly recruited subjects
Plasma samples will be collected from newly recruited subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the endogenous metabolic ratio of 4β-hydroxycholesterol to cholesterol (4β-OHC/C, a marker of CYP3A activity) from early pregnancy through 17 weeks 6 days after delivery
Time Frame: Between 4-13 weeks of pregnancy, and 1-18 weeks postpartum
plasma concentrations
Between 4-13 weeks of pregnancy, and 1-18 weeks postpartum

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of active CYP3A5 phenotype on the 4β-hydroxycholesterol to cholesterol metabolic ratio
Time Frame: Between 4-13 weeks of pregnancy, and 1-18 weeks postpartum
plasma concentrations
Between 4-13 weeks of pregnancy, and 1-18 weeks postpartum
Impact of estradiol concentrations on ratio in the early first trimester of pregnancy
Time Frame: Between 4-13 weeks of pregnancy, and 1-18 weeks postpartum
plasma concentrations
Between 4-13 weeks of pregnancy, and 1-18 weeks postpartum

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

Purdue University

Investigators

  • Principal Investigator: Katherine L Wisner, M.D., M.S., Northwestern University
  • Principal Investigator: Hyunyoung Jeong, PharmD, PhD, Purdue University
  • Principal Investigator: Catherine S Stika, M.D., Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 17, 2022

Primary Completion (Actual)

June 30, 2023

Study Completion (Actual)

June 30, 2023

Study Registration Dates

First Submitted

August 15, 2022

First Submitted That Met QC Criteria

August 15, 2022

First Posted (Actual)

August 17, 2022

Study Record Updates

Last Update Posted (Actual)

April 24, 2024

Last Update Submitted That Met QC Criteria

April 22, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • STU00217170

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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