Mechanisms of Hypertension in Women With Polycystic Ovary Syndrome

NCT04327934 | Terminated Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2000020950R01HL135089-01A1
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Polycystic Ovary Syndrome; Hypertension

Outcome Measures

Primary Outcomes (8)

• 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).

  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.

  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

  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

  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

  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

  Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

• Resting Sympathetic Activity

  Total sympathetic nerve activity

  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).

  Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Secondary Outcomes (2)

• Aldosterone

  Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

• Renal Responses

  Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone

Study Arms (2)

Healthy Control

ACTIVE COMPARATOR

Healthy control participants.

Drug: GnRH antagonist; Drug: GnRH antagonist + MethylTESTOSTERone 5 MG

AE-PCOS

EXPERIMENTAL

Participants with AE-PCOS.

Drug: GnRH antagonist; Drug: GnRH antagonist + MethylTESTOSTERone 5 MG

Interventions

GnRH antagonist DRUG

GnRH antagonist up to 16 days.

Also known as: Antagon

AE-PCOS; Healthy Control

GnRH antagonist + MethylTESTOSTERone 5 MG DRUG

GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.

Also known as: Antagon + MethylTESTOSTERone

AE-PCOS; Healthy Control

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Obese Insulin Resistant (IR) women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Males

Sponsors & Collaborators

• Yale University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

The John B Pierce Laboratory

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Hypertension

Interventions

LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; ganirelix; Methyltestosterone

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Testosterone; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

• Title: Nina Stachenfeld
• Organization: John B. Pierce Laboratory/Yale School of Medicine

nina.stachenfeld@yale.edu

203 562 9901

Study Officials

• Nina Stachenfeld, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2018
• First Posted: March 31, 2020
• Study Start: December 1, 2017
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: February 2, 2024
• Results First Posted: February 2, 2024

Record last verified: 2024-01

Locations

US (1)