Contraception, Pharmacogenomic Drug Interaction
Conditions
Brief summary
The goal of this clinical trial is to evaluate how differences in specific parts of our DNA can influence how individual bodies break down the hormones contained within oral contraceptive pills, which could affect how well these birth control pills work to prevent pregnancy. The investigators are also interested in exploring how these differences in our DNA can also explain why patients taking the exact same formulation of birth control pill will experience very different side effects. The main questions it aims to answer are: * Do individuals with the CYP3A7\*1C variant have increased metabolism of both desogestrel and ethinyl estradiol when taking a combined oral contraceptive pill? * Do individuals with the CYP3A7\*1C variant experience higher rates of breakthrough ovulation while taking a desogestrel/ethinyl estradiol combined oral contraceptive pill? * What novel genetic loci are associated with alterations in steroid hormone pharmacokinetics and pharmacodynamics among a larger cohort of combined oral contraceptive pill users? Participants will take a specific formulation of combined oral contraceptive pill (desogestrel/ethinyl estradiol) and undergo the following procedures: * Blood draw to measure the amount of progestin and estrogen in their system from the combined oral contraceptive pill * Questionnaires to assess side effects possibly caused by the combined oral contraceptive pill * Blood draw to measure endogenous hormone levels and biomarkers that may be affected by the combined oral contraceptive pill * A transvaginal ultrasound to measure any ovarian follicles (optional procedure)
Interventions
DRUGDesogestrel / Ethinyl Estradiol Pill
Standard pill packs containing 21 active pills and 7 placebo pills
Sponsors
Yale University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Female, aged 18-45 years old 4. In good general health as evidenced by medical history and no need for regular intensive medical interventions (e.g., inpatient admissions, surgical treatments). The Principal Investigator will be responsible for determining good general health for potential participants with complicated medical histories. 5. Ability to take oral medication and be willing to adhere to the oral contraceptive pill (DSG/EE) regimen 6. Body-mass index ≥18.5kg/m2 7. Willing to abstain from medications and supplements known to induce/inhibit CYP3A (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort) during the study 8. Normal blood pressure measurement at study screening 9. Negative urine pregnancy test at study screening
Exclusion criteria
1. Currently taking any known CYP3A inducers/inhibitors (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort)43 2. Any medical conditions that affect liver function (e.g., hepatitis, cirrhosis) 3. Contraindications to estrogen-containing contraception (based on category 3 or 4 recommendations in the CDC MEC guidelines42) 1. Current breast cancer or personal history of breast cancer 2. Severe decompensated cirrhosis 3. Personal history of deep venous thrombosis or pulmonary embolism 4. Recent major surgery with prolonged immobilization 5. Diabetes with nephropathy, retinopathy, neuropathy, or other vascular disease 6. Current gallbladder disease 7. Migraine headaches with aura 8. History of malabsorptive bariatric surgery 9. History of cholestasis due to past oral contraceptive pill use 10. Personal history of hypertension 11. Personal history of ischemic heart disease 12. Known thrombogenic mutations 13. Personal history of focal nodular hyperplasia of the liver, hepatocellular adenoma, or malignant hepatoma 14. Multiple sclerosis with prolonged immobility 15. History of peripartum cardiomyopathy 16. Current tobacco smoker and age ≥35 years 17. History of complicated solid organ transplantation 18. Personal history of stroke 19. Personal history of superficial venous thrombosis 20. Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies 21. Complicated valvular heart disease 22. Current use of fosamprenavir or lamotrigine 4. Use of injectable contraceptive method within 6 months or current use of an ENG implant 5. Childbirth within 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum etonogestrel concentration | Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days) | Pharmacokinetic measurement for progestin |
| Serum ethinyl estradiol concentration | Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days) | Pharmacokinetic measurement for estrogen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum estradiol concentration | Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days) | Pharmacodynamic measurement of endogenous estrogen |
| Serum progesterone concentration | Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days) | Pharmacodynamic measurement of endogenous progesterone |
| Modified Hoogland score | Measured on Cycle 1, Day 22 (optional study procedure) (each cycle is 28 days) | Calculated based on serum estradiol, serum progesterone, and follicle-like structures. found on transvaginal ultrasound. Scores range from 1 to 5, with a higher score indicating a higher likelihood of pending ovulation with a score of 5 indicating suspected ovulation |
| Positive and Negative Affect Scheduled | Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeated measurements again in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days) | Questionnaire designed to assess current affect. Scores range from 10-50 for positive affect items and 10-50 for negative affect items, with higher scores representing more positive affect or negative affect, respectively. |
| Sex hormone binding globulin levels | Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeat measurements in cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days) | Marker of estrogenicity |
| Serum albumin concentration | Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeat measurements in cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days) | Protein binding compound |
Countries
United States
Contacts
CONTACTAaron M Lazorwitz, MD, PhD
PRINCIPAL_INVESTIGATORAaron M Lazorwitz, MD, PhD
Yale University
Outcome results
None listed