Oral Contraceptive Pill (OCP) Pharmacogenomics

Contraception Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06334315
• Other study ID #: 2000037337
• Secondary ID: R01HD111436
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: July 2024
• Est. completion date: May 2028

Study information

• Verified date: May 2024
• Source: Yale University
• Contact: Aaron M Lazorwitz, MD, PhD
• Phone: 2037854688
• Email: aaron.lazorwitz[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 700
• Est. completion date: May 2028
• Est. primary completion date: May 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Contraception

Intervention

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

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Yale	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum etonogestrel concentration	Pharmacokinetic measurement for progestin	Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days)
Primary	Serum ethinyl estradiol concentration	Pharmacokinetic measurement for estrogen	Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days)
Secondary	Serum estradiol concentration	Pharmacodynamic measurement of endogenous estrogen	Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)
Secondary	Serum progesterone concentration	Pharmacodynamic measurement of endogenous progesterone	Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)
Secondary	Modified Hoogland score	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	Measured on Cycle 1, Day 22 (optional study procedure) (each cycle is 28 days)
Secondary	Positive and Negative Affect Scheduled	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.	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)
Secondary	Sex hormone binding globulin levels	Marker of estrogenicity	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)
Secondary	Serum albumin concentration	Protein binding compound	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)