Mechanisms of Hypertension in Women With Polycystic Ovary Syndrome

Early Phase 1

Terminated

• Conditions: Polycystic Ovary Syndrome; Hypertension
• Interventions: Drug: GnRH antagonist; Drug: GnRH antagonist + MethylTESTOSTERone 5 MG

• Registration Number: NCT04327934
• Lead Sponsor: Yale University

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-12-01
• Study First Submitted: 2018-10-17
• Study First Submitted QC: 2020-03-27
• Study First Posted: 2020-03-31
• Primary Completion: 2022-06-30
• Study Completion: 2022-06-30
• Results First Submitted: 2023-02-24
• Status Verified: 2024-01
• Results First Submitted QC: 2024-01-04
• Last Update Submitted: 2024-01-04
• Results First Posted: 2024-02-02
• Last Update Posted: 2024-02-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 28

Inclusion Criteria

• Clinical Diagnosis of Polycystic Ovary Syndrome
• Able to inject study drug
• Able to swallow pills

Controls:

-Diagnosis of Insulin resistance

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Exclusion Criteria

• Any woman that does not fit the inclusion criteria
• Males

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Control	GnRH antagonist	Healthy control participants.
Healthy Control	GnRH antagonist + MethylTESTOSTERone 5 MG	Healthy control participants.
AE-PCOS	GnRH antagonist	Participants with AE-PCOS.
AE-PCOS	GnRH antagonist + MethylTESTOSTERone 5 MG	Participants with AE-PCOS.

Primary Outcome Measures

Name	Time	Method
Free Plasma Testosterone Levels	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	Concentration of testosterone in blood.
Baroreflex Response to LBNP	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).
Renal Response to LBNP	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	POST Lower body negative pressure Plasma renin activity
Resting Systolic Blood Pressure	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	Blood pressure prior to lower body negative pressure
Renal Responses to LBNP	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	PRE lower body negative pressure Plasma renin activity
Final Systolic Blood Pressure	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
Sympathetic Baroreflex	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).
Resting Sympathetic Activity	Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone	Total sympathetic nerve activity

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The John B Pierce Laboratory; 🇺🇸 New Haven, Connecticut, United States