Contraceptive UsagePhase 4COC+DHEANCT03418363
How DHEA Supplements Affect Coagulation in Women Using Birth Control Pills
A Phase 4 study testing DHEA Oral Capsule in people with Contraceptive Usage and Coagulation, run by Oregon Health and Science University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 44 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraceptive Usage, Coagulation
- What is being tested?
- DHEA Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2018to 11 Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 44 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
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)
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.
Read the 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.
- Conditions
- Contraceptive Usage, Coagulation
- Being tested
- DHEA Oral Capsule, Placebo Oral Capsule
- Keywords
- Oral contraceptives, Venous thromboembolism, androgenic combined oral contraception
- Medical subject headings
- Contraception Behavior, Thrombosis, Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DHEA Oral CapsuleDietary supplement
Daily 100mg DHEA supplement
Placebo Oral CapsuleOther
Daily oral capsule
| Study group | Role | What they receive |
|---|---|---|
| DHEA Oral Capsule | Active comparator | Subjects will take 100mg DHEA (dehydroepiandrosterone) daily Receives: Dietary Supplement: DHEA Oral Capsule |
| Placebo Oral Capsule | Placebo comparator | Not described Receives: Other: Placebo Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 3-month plasma levels of APC-r
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).
Measured: Baseline & Study Completion (month 3)
Change in 3-month plasma levels of protein S
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).
Measured: Baseline & Study Completion (month 3)
Change in 3-month serum levels of SHBG
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).
Measured: Baseline & Study Completion (month 3)
Change in 3-month serum levels of ethinyl estradiol
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).
Measured: Baseline & Study Completion (month 3)
Change in 3-month serum levels of DHEA
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).
Measured: Baseline & Study Completion (month 3)
Change in 3-month serum levels of free and total testosterone
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).
Measured: Baseline & Study Completion (month 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2018
- Study start16 Jan 2018
- Primary completion11 Mar 2019
- Study completion11 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Contraceptive UsageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeffrey Jensen, Oregon Health and Science University
- Investigators
- Jeffrey Jensen, MD, MPH, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03418363
- Sponsor's protocol ID
- OHSU IRB# 17651
- Acronym
- COC+DHEA
- Status last verified
- Jan 2020
- First submitted
- 3 Nov 2017
- Last updated
- 23 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03418363
- Acronym / sponsor ID
- COC+DHEA / OHSU IRB# 17651
- Conditions
- Contraceptive Usage, Coagulation
- Keywords
- Oral contraceptives, Venous thromboembolism, androgenic combined oral contraception
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- 16 Jan 2018 (actual)
- Primary completion
- 11 Mar 2019 (actual)
- Study completion
- 11 Dec 2019 (actual)
- First posted
- 1 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DHEA Oral Capsule | Active comparator | Dietary Supplement: DHEA Oral CapsuleSubjects will take 100mg DHEA (dehydroepiandrosterone) daily |
| Placebo Oral Capsule | Placebo comparator | Other: Placebo Oral Capsule |
Who may qualify
- Ages
- 18 to 44 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DHEA Oral CapsuleDaily 100mg DHEA supplement | Dietary supplement | DHEA Oral Capsule |
| Placebo Oral CapsuleDaily oral capsule | Other | Placebo Oral Capsule |
Primary outcome
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).
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).
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).
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).
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).
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Jensen, MD, MPH principal investigator
Oregon Health and Science University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing DHEA Oral Capsule in people with Contraceptive Usage and Coagulation, run by Oregon Health and Science University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in 3-month plasma levels of APC-r (time frame: Baseline & Study Completion (month 3)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2020.