Polycystic Ovary SyndromeEarly Phase 1NCT04327934

Mechanisms of Hypertension in Women With Polycystic Ovary Syndrome

A Early Phase 1 study testing GnRH antagonist and GnRH antagonist + MethylTESTOSTERone 5 MG in people with Polycystic Ovary Syndrome and Hypertension, run by Yale University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Women with androgen excess polycystic ovary syndrome (AE-PCOS) leads to hypertension. Read more about this study

Who is it for?: Ages 18 to 35 years, women onlyHealthy volunteers can take part
Conditions the study is for: Polycystic Ovary Syndrome, Hypertension
What is being tested?: GnRH antagonist and GnRH antagonist + MethylTESTOSTERone 5 MG
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 1 siteUnited States
Study dates: 1 Dec 2017to 30 Jun 2022
Phase: Early Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 35 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Clinical Diagnosis of Polycystic Ovary Syndrome
Able to inject study drug
Able to swallow pills
Controls:
-Diagnosis of Insulin resistance

Who cannot join

Any woman that does not fit the inclusion criteria
Males

Trial locations and contacts

1 site in 1 country.

United States1 site

The John B Pierce Laboratory
New Haven, Connecticut, 06519

Other trials in United States

About this study

Women with androgen excess polycystic ovary syndrome (AE-PCOS) leads to hypertension.

Read the detailed description

Our scientific premise is that in AE-PCOS women, the androgen-dominant hormonal milieu causes BP increases via sympathetic activation, vasoconstriction and renal sympathetic nervous system activation. Moreover, this androgen-dominant milieu increases BP via activation of the renin-angiotensin system.

Conditions: Polycystic Ovary Syndrome, Hypertension
Being tested: GnRH antagonist, GnRH antagonist + MethylTESTOSTERone 5 MG
Medical subject headings: Polycystic Ovary Syndrome, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GnRH antagonistDrug
Also called Antagon
GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MGDrug
Also called Antagon + MethylTESTOSTERone
GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.

Study groups in NCT04327934
Study group	Role	What they receive
Healthy Control	Active comparator	Healthy control participants. Receives: Drug: GnRH antagonist; Drug: GnRH antagonist + MethylTESTOSTERone 5 MG
AE-PCOS	Experimental	Participants with AE-PCOS. Receives: Drug: GnRH antagonist; Drug: GnRH antagonist + MethylTESTOSTERone 5 MG

What is being measured

The primary outcome is the main question the study is designed to answer.

Baroreflex Response to LBNP
forearm blood flow (ultrasound)/mean arterial pressure as a linear function of lower body negative pressure. This is an important measure of autonomic control of blood pressure. Indicating the the sensitivity of changes in vessel diameter in response to blood pooling (induced by lower body negative pressure).
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Free Plasma Testosterone Levels
Concentration of testosterone in blood.
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Renal Response to LBNP
POST Lower body negative pressure Plasma renin activity
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Renal Responses to LBNP
PRE lower body negative pressure Plasma renin activity
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Resting Systolic Blood Pressure
Blood pressure prior to lower body negative pressure
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Final Systolic Blood Pressure
SBP at the end of lower body negative pressure
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Resting Sympathetic Activity
Total sympathetic nerve activity
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Sympathetic Baroreflex
microneurography, diastolic blood pressure (finipres) This is an important measure of autonomic control of blood pressure. Indicating the the sensitivity of changes in muscle sympathetic nerve activity in response to small changes in blood pressure induced by drug perfusion (modified Oxford).
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Secondary outcomes (2)

Aldosterone
Plasma aldosterone concentration
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Renal Responses
P[ACE], angiotensin-converting enzyme
Measured: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Dec 201730 Jun 2022

First posted31 Mar 2020
Study start1 Dec 2017
Primary completion30 Jun 2022
Study completion30 Jun 2022

Why it stopped: Unble to complete all arms of the planned study due to Covid stoppage and difficulty with recruiting and getting enrolled participants to return post Covid.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Polycystic Ovary SyndromeStudies of the same condition, open and under way.
More trials run by Yale UniversityThe sponsor's other registered studies.
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: Early Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04327934
Sponsor's protocol ID: 2000020950
Other IDs: R01HL135089-01A1
Status last verified: Jan 2024
First submitted: 17 Oct 2018
Last updated: 2 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Young BE, Colburn A, Oldham ZR, Berbrier D, Usselman CW, Stone T, Fadel PJ, Stachenfeld NS. Combined androgen excess polycystic ovary syndrome and obesity are associated with elevated beat-to-beat blood pressure variability in adult women. Am J Physiol Heart Circ Physiol. 2026 Aug 1;331(2):H374-H381. doi: 10.1152/ajpheart.00275.2026. Epub 2026 Jun 15.
PubMed 42294856

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Polycystic Ovary Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Mechanisms of Hypertension in Women With Polycystic Ovary Syndrome
ClinicalTrials.gov ID: NCT04327934
Acronym / sponsor ID: 2000020950
Conditions: Polycystic Ovary Syndrome, Hypertension
Phase: Early Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Unble to complete all arms of the planned study due to Covid stoppage and difficulty with recruiting and getting enrolled participants to return post Covid.
Enrolment: 28 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: 1 Dec 2017 (actual)
Primary completion: 30 Jun 2022 (actual)
Study completion: 30 Jun 2022 (actual)
First posted: 31 Mar 2020 (actual)
Results: Posted 2 Feb 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Women with androgen excess polycystic ovary syndrome (AE-PCOS) leads to hypertension.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Healthy Control	Active comparator	Drug: GnRH antagonist, Drug: GnRH antagonist + MethylTESTOSTERone 5 MGHealthy control participants.
AE-PCOS	Experimental	Drug: GnRH antagonist, Drug: GnRH antagonist + MethylTESTOSTERone 5 MGParticipants with AE-PCOS.

Who may qualify

Ages: 18 to 35 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Clinical Diagnosis of Polycystic Ovary Syndrome
Able to inject study drug
Able to swallow pills
-Diagnosis of Insulin resistance

Key exclusion criteria (2 listed)

Any woman that does not fit the inclusion criteria
Males

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
GnRH antagonistAlso: AntagonGnRH antagonist up to 16 days.	Drug	AE-PCOS, Healthy Control
GnRH antagonist + MethylTESTOSTERone 5 MGAlso: Antagon + MethylTESTOSTERoneGnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.	Drug	AE-PCOS, Healthy Control

Primary outcome

Baroreflex Response to LBNP
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
forearm blood flow (ultrasound)/mean arterial pressure as a linear function of lower body negative pressure. This is an important measure of autonomic control of blood pressure. Indicating the the sensitivity of changes in vessel diameter in response to blood pooling (induced by lower body negative pressure).
Free Plasma Testosterone Levels
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Concentration of testosterone in blood.
Renal Response to LBNP
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
POST Lower body negative pressure Plasma renin activity
Renal Responses to LBNP
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
PRE lower body negative pressure Plasma renin activity
Resting Systolic Blood Pressure
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Blood pressure prior to lower body negative pressure
Final Systolic Blood Pressure
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
SBP at the end of lower body negative pressure
Resting Sympathetic Activity
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Total sympathetic nerve activity
Sympathetic Baroreflex
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
microneurography, diastolic blood pressure (finipres) This is an important measure of autonomic control of blood pressure. Indicating the the sensitivity of changes in muscle sympathetic nerve activity in response to small changes in blood pressure induced by drug perfusion (modified Oxford).

2 secondary outcomes

Aldosterone
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Renal Responses
Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Results and safety

Results posted to the registry on 2 Feb 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Healthy Control	14	7
AE-PCOS	14	9

Primary outcome: Baroreflex Response to LBNP

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone. Mean (Standard Deviation). Unit: Arbitrary Units/Beat/mmHg

Measure	Healthy Control n = 7	AE-PCOS n = 9
Baseline	0.98 (1.35)	1.36 (0.96)
GnRH antagonist	1.9 (3.0)	4.28 (6.51)
GnRH antagonist with GnRH + Testosterone	0.68 (0.65)	1.46 (0.76)

Healthy Control vs AE-PCOS: p = 0.018, ANOVA

Primary outcome: Free Plasma Testosterone Levels

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone. Mean (Standard Deviation). Unit: mg/dL

Measure	Healthy Control n = 7	AE-PCOS n = 9
Baseline	0.76 (0.57)	2.72 (1.13)
GnRH	0.67 (0.39)	1.06 (0.31)
GnRH + Testosterone	1.34 (0.23)	2.19 (0.19)

Healthy Control vs AE-PCOS: p <0.016, ANOVA
Healthy Control: p = 0.08, ANOVA

Primary outcome: Renal Response to LBNP

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone. Mean (Standard Deviation). Unit: ng/mL ANG/hour

Measure	Healthy Control n = 7	AE-PCOS n = 9
Baseline	1.05 (0.82)	1.10 (0.46)
GnRH	0.54 (0.33)	1.14 (1.31)
GnRH+Testosterone	0.83 (0.71)	1.36 (1.51)

Primary outcome: Renal Responses to LBNP

Time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone. Mean (Standard Deviation). Unit: ng/mL ANG/hour

Measure	Healthy Control n = 7	AE-PCOS n = 9
Baseline	0.53 (0.48)	0.85 (0.97)
GnRH	0.42 (0.21)	0.79 (1.24)
GnRH + Testosterone	0.63 (0.43)	0.76 (0.75)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Six to eight weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Healthy Control	0 of 14 (0%)	1 of 14 (7.1%)	0 of 14
AE-PCOS	0 of 14 (0%)	1 of 14 (7.1%)	0 of 14

Limitations and caveats (from the sponsor): Our primary limitation was stoppage due to Covid (our laboratory was forced to close). We also had a very challenging time recruiting subjects when we reopened after the three-month closure under new rules. Subjects who had been enrolled did not return, and new subjects were difficult to recruit. Thus, we were not able to complete all arms of the planned study. We were able to answer our primary questions regarding autonomic function in women with PCOS.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42294856Young BE, Colburn A, Oldham ZR, Berbrier D, Usselman CW, Stone T, Fadel PJ, Stachenfeld NS. Combined androgen excess polycystic ovary syndrome and obesity are associated with elevated beat-to-beat blood pressure variability in adult women. Am J Physiol Heart Circ Physiol. 2026 Aug 1;331(2):H374-H381. doi: 10.1152/ajpheart.00275.2026. Epub 2026 Jun 15.

Related trials for Polycystic Ovary Syndrome

Recruiting
Efficacy of Ovarian Drilling Via vNOTES Laparoscopy in Patients With PCOS
PCOS (Polycystic Ovary Syndrome)
RecruitingPhase 1
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Anovulatory Infertility
RecruitingObservational study
The Value of LC-MS/MS Detection of Androgen Profiles in the Diagnosis of PCOS: A Prospective, Multicenter Real-world Study
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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.

Nina Stachenfeld, PhD principal investigator

Yale University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 5 inclusion and 2 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: stopped early, as of the sponsor's last update on 2 Feb 2024. 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. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Baroreflex Response to LBNP (time frame: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04327934, which also lists 1 linked publication.

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 2 Feb 2024.