Clinical trial NCT03092037: Pharmacogenomics of Contraception: Genetic Variants and Etonogestrel Pharmacokinetics
Official title: Pharmacogenomics of Contraception: Genetic Variants and Etonogestrel Pharmacokinetics
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Contraception
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Society of Family Planning
First posted: 2017-03-27
Enrollment: 900
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We will enroll 900 women of reproductive age (18-45 years) who have had an ENG contraceptive implant in place for 12-36 months.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of genetic variants in cases versus controls
timeFrame: DNA extracted from whole blood specimens will be genotyped at the conclusion of enrollment, approximately 12 months.
measure: Genome wide genotyping results
timeFrame: DNA extracted from whole blood specimens will be genotyped at the conclusion of enrollment, approximately 15 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Aaron Lazorwitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lazorwitz A, Sheeder J, Teal S. Variability in repeat serum etonogestrel concentrations among contraceptive implant users during the steady-release pharmacokinetic period. Contraception. 2022 Apr;108:65-68. doi: 10.1016/j.contraception.2021.12.008. Epub 2021 Dec 29.
citation: Lazorwitz A, Aquilante CL, Shortt JA, Sheeder J, Teal S, Gignoux CR. Applicability of ancestral genotyping in pharmacogenomic research with hormonal contraception. Clin Transl Sci. 2021 Sep;14(5):1713-1718. doi: 10.1111/cts.13014. Epub 2021 May 2.
citation: Lazorwitz A, Sheeder J, Teal S. An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users. Eur J Contracept Reprod Health Care. 2021 Aug;26(4):323-325. doi: 10.1080/13625187.2021.1887475. Epub 2021 Feb 17.
citation: Lazorwitz A, Aquilante CL, Sheeder J, Guiahi M, Teal S. Relationship between patient characteristics and serum etonogestrel concentrations in contraceptive implant users. Contraception. 2019 Jul;100(1):37-41. doi: 10.1016/j.contraception.2019.03.045. Epub 2019 Apr 10.
citation: Lazorwitz A, Aquilante CL, Oreschak K, Sheeder J, Guiahi M, Teal S. Influence of Genetic Variants on Steady-State Etonogestrel Concentrations Among Contraceptive Implant Users. Obstet Gynecol. 2019 Apr;133(4):783-794. doi: 10.1097/AOG.0000000000003189.