Pharmacogenomics of Contraception: Genetic Variants and Etonogestrel Pharmacokinetics

Completed

• Conditions: Contraception
• Interventions: Procedure: Blood draw

• Registration Number: NCT03092037
• Lead Sponsor: University of Colorado, Denver

Brief Summary

The proposed study will investigate the relationship between genetic variants and serum contraceptive hormone levels, specifically the progestin etonogestrel. This study will provide the foundation for future pharmacogenomic investigations of more commonly used contraceptive methods with higher failure rates.

Detailed Description

Approximately 700 reproductive age women (18-45) with an Etonogestrel (ENG) contraceptive implant in place for more than 1 year will be enrolled. Participants will undergo a blood draw for measurement of ENG concentration (serum) and genotyping (whole blood) and complete a questionnaire regarding their demographics and contraceptive, gynecological, and obstetrical history. The research investigators will also consent participants for use of their genetic samples and clinical data in future unspecified research.

The serum samples will be de-identified for ENG analysis, which will be done using a liquid chromatography-mass spectrometry method. Additional whole blood samples collected at the enrollment visit will undergo DNA extraction. A candidate gene study was conducted using the first 350 participants. The research investigators selected 120 genetic variants for 14 target genes involved in progestin metabolism, regulation, and function for this candidate gene study. A Genome Wide Association Study will be performed using all 700 participants. Genotyping will be performed using a custom MultiEthnic Global Array chip through the Colorado Center for Personalized Medicine.

Study Timeline

• Study First Submitted: 2017-03-10
• Study First Submitted QC: 2017-03-21
• Study Start: 2017-03-23
• Study First Posted: 2017-03-27
• Primary Completion: 2022-04-29
• Study Completion: 2022-04-29
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-12
• Last Update Posted: 2022-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 900

Inclusion Criteria

• women of reproductive age (18-45 years)
• have had an ENG contraceptive implant in place for 12-36 months

Exclusion Criteria

• Use of medications or supplements in the past four weeks which could impact serum ENG levels through inhibition or induction of CYP enzymes (specifically CYP-3A4)
• Medical conditions that could impact baseline liver function (e.g. hepatitis, cirrhosis)
• Body mass index (BMI) less than 18.5

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
All participants (side-effects)	Blood draw	All participants will have their blood drawn and complete a brief questionnaire regarding bleeding patterns and side-effects. DNA will be extracted from whole blood and genotyping data will be analyzed for associations with specific bleeding patterns and side-effects.
All participants	Blood draw	All participants will have their blood drawn. DNA will be extracted from whole blood, and serum will be analyzed for ENG concentrations. Genotyping data will be analyzed for associations with serum ENG concentrations.

Primary Outcome Measures

Name	Time	Method
Genome wide genotyping results	DNA extracted from whole blood specimens will be genotyped at the conclusion of enrollment, approximately 15 months.	Participants will undergo genotyping using a custom MEGA chip at the Colorado Center for Personalized Medicine. Imputation of the chip results will be performed.
Proportion of genetic variants in cases versus controls	DNA extracted from whole blood specimens will be genotyped at the conclusion of enrollment, approximately 12 months.	Genetic variants will be analyzed using a Taqman microarray chip for 120 pre-selected variants

Trial Locations

Locations (1)

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States