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How DHEA Supplements Affect Coagulation in Women Using Birth Control Pills (COC+DHEA)

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ClinicalTrials.gov Identifier: NCT03418363
Recruitment Status : Recruiting
First Posted : February 1, 2018
Last Update Posted : February 1, 2018
Sponsor:
Information provided by (Responsible Party):
Jeffrey Jensen, Oregon Health and Science University

Brief Summary:
A randomized study is to learn more about how a supplement called DHEA (dehydroepiandrosterone) affects clotting factors in women taking combined oral contraceptive pills. Current research suggests that the progestin hormone in a specific type of birth control pill may increase a woman's blood clot risk. However, it is unknown exactly how the progestin causes the increased risk. This study aims to learn if taking a daily dose of supplemental androgen (dehydroepiandrosterone, or DHEA) in addition to birth control pills containing DRSP affects proteins related to coagulation.

Condition or disease Intervention/treatment Phase
Contraceptive Usage Coagulation Dietary Supplement: DHEA Oral Capsule Other: Placebo Oral Capsule Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Double blind
Primary Purpose: Basic Science
Official Title: Effect of the Addition of an Oral Androgen (Dehydroepiandrosterone) on Hepatic Globulins in Users of an Antiandrogenic Combined Oral Contraceptive (Ethinyl Estradiol/Drospirenone)
Actual Study Start Date : January 16, 2018
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
Active Comparator: DHEA Oral Capsule
Subjects will take 100mg DHEA (dehydroepiandrosterone) daily
Dietary Supplement: DHEA Oral Capsule
Daily 100mg DHEA supplement

Placebo Comparator: Placebo Oral Capsule Other: Placebo Oral Capsule
Daily oral capsule




Primary Outcome Measures :
  1. Change in 3-month plasma levels of APC-r [ Time Frame: 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).

  2. Change in 3-month plasma levels of protein S [ Time Frame: 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).

  3. Change in 3-month serum levels of SHBG [ Time Frame: 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).

  4. Change in 3-month serum levels of ethinyl estradiol [ Time Frame: 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).

  5. Change in 3-month serum levels of DHEA [ Time Frame: 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).

  6. Change in 3-month serum levels of free and total testosterone [ Time Frame: 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).



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Ages Eligible for Study:   18 Years to 44 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03418363


Contacts
Contact: Women's Health Research Unit Confidential Recruitment Line 503-494-3666 whru@ohsu.edu

Locations
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Women's Health Research Unit    503-494-3666    whru@ohsu.edu   
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Jeffrey Jensen, MD, MPH Oregon Health and Science University

Responsible Party: Jeffrey Jensen, Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT03418363     History of Changes
Other Study ID Numbers: OHSU IRB# 17651
First Posted: February 1, 2018    Key Record Dates
Last Update Posted: February 1, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jeffrey Jensen, Oregon Health and Science University:
Oral contraceptives
Venous thromboembolism
androgenic combined oral contraception

Additional relevant MeSH terms:
Contraceptive Agents
Contraceptives, Oral
Dehydroepiandrosterone
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Female
Adjuvants, Immunologic
Immunologic Factors