- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03418363
How DHEA Supplements Affect Coagulation in Women Using Birth Control Pills (COC+DHEA)
Effect of the Addition of an Oral Androgen (Dehydroepiandrosterone) on Hepatic Globulins in Users of an Antiandrogenic Combined Oral Contraceptive (Ethinyl Estradiol/Drospirenone)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
While the pro-thrombotic effects of estrogens are well established in women using combined oral contraception (COC), controversy exists over whether the various synthetic progestogens (progestins) used in combination with ethinyl estradiol in COC formulations may modify the risk of venous thromboembolism (VTE). Several studies have demonstrated that different types of progestins used in COCs influence the magnitude of the estrogen-induced changes in coagulation pathway proteins. However, since hepatocytes do not express progesterone receptor, any activity of a progestin must be indirect. While all progestins on the market are strong agonists for the progesterone receptor (PR), most have variable affinity for the androgen receptor (AR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR). Generations of progestins have been developed, each successive generation exhibiting decreasing levels of androgenicity. Recent epidemiologic studies have suggested an increased risk of VTE in women using low-androgen progestins relative to those using levonorgestrel-containing products. Although no pattern of hepatic globulin changes has been validated as a surrogate marker for thrombosis risk, the overall magnitude of change in various hepatic proteins involved in coagulation is greater with the newer low-androgenic progestins compared to levonorgestrel, leading some experts to suggest that a progestin's androgenic profile may influence the risk of thrombosis. However, a series of well-designed large prospective cohort studies have not confirmed the increased risk of VTE with low-androgen progestins.
A major problem with reconciling the conflicting results from epidemiologic and prospective studies has been the lack of a clear mechanism, as no studies have demonstrated whether these observed changes are mediated through androgen receptor activity. We hypothesize that androgen receptor activity opposes the estrogen receptor-mediated increase in hepatic clotting factors in women using combined oral contraceptives. To test this hypothesis, we propose a randomized clinical trial in which we will enroll healthy women using combined oral contraception containing ethinyl estradiol (EE) with an antiandrogenic progestin (drospirenone, DRSP). Participants will be randomized to treatment with oral androgen (dehydroepiandrosterone, DHEA) or placebo, and we will collect whole blood samples to measure coagulation pathway-related hepatic globulins (APC-r, Protein S, SHBG) before and after treatment.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Oregon
-
Portland, Oregon, United States, 97239
- Oregon Health & Science University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Women of reproductive age (18-44 years) in generally good health and with body mass index (BMI) between 18 and 35kg/m2
- Premenopausal, with uterus and at least one ovary intact
- Current users (at least 3 months) of combined oral contraception consisting of 0.02 mg (milligram) ethinyl estradiol and 3 mg drospirenone
- Willing to continue use of current combined oral contraception for the next three menstrual cycles
- Have a prescription for combined oral contraception consisting of ethinyl estradiol and drospirenone for the next four cycles
- Not currently using androgen supplementation
- Willing and able to sign the informed consent
- Willing to comply with the study requirements and visit schedule
- No desire to conceive during study participation, approximately 3 months
Exclusion Criteria:
- Currently enrolled in another clinical trial
- Contraindications to androgen supplementation; history of polycystic ovarian syndrome (PCOS)
- Known or suspected pregnancy, pregnancy within 3 months before study enrollment, or desire to conceive during study participation
- Currently breastfeeding
- Known or suspected alcoholism or drug abuse
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: DHEA Oral Capsule
Subjects will take 100mg DHEA (dehydroepiandrosterone) daily
|
Daily 100mg DHEA supplement
|
Placebo Comparator: Placebo Oral Capsule
|
Daily oral capsule
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in 3-month plasma levels of APC-r
Time Frame: Baseline & Study Completion (month 3)
|
Access change in blood levels from baseline (Visit 1) to study completion visit (Visit 2).
Collection of whole blood samples from participants to assess change in levels of APC-r after randomization to DHEA supplementation or placebo for 3 cycles (approximately 3 months).
|
Baseline & Study Completion (month 3)
|
Change in 3-month plasma levels of protein S
Time Frame: Baseline & Study Completion (month 3)
|
Access change in blood levels from baseline (Visit 1) to study completion visit (Visit 2).
Collection of whole blood samples from participants to assess change in levels of protein S after randomization to DHEA supplementation or placebo for 3 cycles (approximately 3 months).
|
Baseline & Study Completion (month 3)
|
Change in 3-month serum levels of SHBG
Time Frame: Baseline & Study Completion (month 3)
|
Access change in blood levels from baseline (Visit 1) to study completion visit (Visit 2).
Collection of whole blood samples from participants to assess change in levels of SHBG after randomization to DHEA supplementation or placebo for 3 cycles (approximately 3 months).
|
Baseline & Study Completion (month 3)
|
Change in 3-month serum levels of ethinyl estradiol
Time Frame: Baseline & Study Completion (month 3)
|
Access change in blood levels from baseline (Visit 1) to study completion visit (Visit 2).
Collection of whole blood samples from participants to assess change in levels of ethinyl estradiol after randomization to DHEA supplementation or placebo for 3 cycles (approximately 3 months).
|
Baseline & Study Completion (month 3)
|
Change in 3-month serum levels of DHEA
Time Frame: Baseline & Study Completion (month 3)
|
Access change in blood levels from baseline (Visit 1) to study completion visit (Visit 2).
Collection of whole blood samples from participants to assess change in levels of DHEA after randomization to DHEA supplementation or placebo for 3 cycles (approximately 3 months).
|
Baseline & Study Completion (month 3)
|
Change in 3-month serum levels of free and total testosterone
Time Frame: Baseline & Study Completion (month 3)
|
Access change in blood levels from baseline (Visit 1) to study completion visit (Visit 2).
Collection of whole blood samples from participants to assess change in levels of total testosterone and free testosterone (calculated using serum albumin) after randomization to DHEA supplementation or placebo for 3 cycles (approximately 3 months).
|
Baseline & Study Completion (month 3)
|
Collaborators and Investigators
Investigators
- Principal Investigator: Jeffrey Jensen, MD, MPH, Oregon Health and Science University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- OHSU IRB# 17651
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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