Oral Contraceptive Pill (OCP) Pharmacogenomics

Official title

Influence of Genetics Variants on the Pharmacokinetics and Pharmacodynamics of Combined Oral Contraceptive Pill Users

Overview

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

• Drug Desogestrel / Ethinyl Estradiol Pill
  Standard pill packs containing 21 active pills and 7 placebo pills

Primary outcome measures

• Serum etonogestrel concentration [Time frame: Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days)]
• Serum ethinyl estradiol concentration [Time frame: Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days)]

Secondary outcome measures (6)

• Serum estradiol concentration [Time frame: Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)]
• Serum progesterone concentration [Time frame: Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)]
• Modified Hoogland score [Time frame: Measured on Cycle 1, Day 22 (optional study procedure) (each cycle is 28 days)]
• Positive and Negative Affect Scheduled [Time frame: 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)]
• Sex hormone binding globulin levels [Time frame: 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)]
• Serum albumin concentration [Time frame: 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)]

Eligibility criteria

Inclusion criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Female, aged 18-45 years old
• 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.
• Ability to take oral medication and be willing to adhere to the oral contraceptive pill (DSG/EE) regimen
• Body-mass index ≥18.5kg/m2
• Willing to abstain from medications and supplements known to induce/inhibit CYP3A (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort) during the study
• Normal blood pressure measurement at study screening
• Negative urine pregnancy test at study screening

Exclusion criteria

• Currently taking any known CYP3A inducers/inhibitors (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort)43
• Any medical conditions that affect liver function (e.g., hepatitis, cirrhosis)
• Contraindications to estrogen-containing contraception (based on category 3 or 4 recommendations in the CDC MEC guidelines42)

• Current breast cancer or personal history of breast cancer
• Severe decompensated cirrhosis
• Personal history of deep venous thrombosis or pulmonary embolism
• Recent major surgery with prolonged immobilization
• Diabetes with nephropathy, retinopathy, neuropathy, or other vascular disease
• Current gallbladder disease
• Migraine headaches with aura
• History of malabsorptive bariatric surgery
• History of cholestasis due to past oral contraceptive pill use
• Personal history of hypertension
• Personal history of ischemic heart disease
• Known thrombogenic mutations
• Personal history of focal nodular hyperplasia of the liver, hepatocellular adenoma, or malignant hepatoma
• Multiple sclerosis with prolonged immobility
• History of peripartum cardiomyopathy
• Current tobacco smoker and age ≥35 years
• History of complicated solid organ transplantation
• Personal history of stroke
• Personal history of superficial venous thrombosis
• Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies
• Complicated valvular heart disease
• Current use of fosamprenavir or lamotrigine
• Use of injectable contraceptive method within 6 months or current use of an ENG implant
• Childbirth within 6 months

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• University of Colorado Anschutz Medical Campus — Aurora
• Yale University — New Haven

Identifiers

NCT: NCT06334315 · 2000037337 · R01HD111436

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗