Trial Outcomes & Findings for Mechanisms of Hypertension in Women With Polycystic Ovary Syndrome (NCT NCT04327934)
NCT ID: NCT04327934
Last Updated: 2024-02-02
Results Overview
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).
Recruitment status
TERMINATED
Study phase
EARLY_PHASE1
Target enrollment
28 participants
Primary outcome timeframe
Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone
Results posted on
2024-02-02
Participant Flow
We will recruit subjects using flyers, our clinics, and social media. Dates 12/01/2017 - 04/29/2022; We were not able to reach recruit goals because our laboratory closed during Covid. When we reopened, we lost a one interested subject, and found greater challenges to recruit subjects.
Participant milestones
| Measure |
Healthy Control
Healthy control participants.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
14
|
|
Overall Study
COMPLETED
|
7
|
9
|
|
Overall Study
NOT COMPLETED
|
7
|
5
|
Reasons for withdrawal
| Measure |
Healthy Control
Healthy control participants.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Overall Study
Did not qualify
|
7
|
4
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Mechanisms of Hypertension in Women With Polycystic Ovary Syndrome
Baseline characteristics by cohort
| Measure |
Healthy Control
n=7 Participants
Healthy control participants.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
28 years
STANDARD_DEVIATION 6 • n=5 Participants
|
24 years
STANDARD_DEVIATION 5 • n=7 Participants
|
26 years
STANDARD_DEVIATION 6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
9 participants
n=7 Participants
|
16 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosteroneforearm 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).
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Baroreflex Response to LBNP
Baseline
|
0.98 Arbitrary Units/Beat/mmHg
Standard Deviation 1.35
|
1.36 Arbitrary Units/Beat/mmHg
Standard Deviation 0.96
|
|
Baroreflex Response to LBNP
GnRH antagonist
|
1.9 Arbitrary Units/Beat/mmHg
Standard Deviation 3.0
|
4.28 Arbitrary Units/Beat/mmHg
Standard Deviation 6.51
|
|
Baroreflex Response to LBNP
GnRH antagonist with GnRH + Testosterone
|
0.68 Arbitrary Units/Beat/mmHg
Standard Deviation 0.65
|
1.46 Arbitrary Units/Beat/mmHg
Standard Deviation 0.76
|
PRIMARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of TestosteroneConcentration of testosterone in blood.
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Free Plasma Testosterone Levels
GnRH
|
0.67 mg/dL
Standard Deviation 0.39
|
1.06 mg/dL
Standard Deviation 0.31
|
|
Free Plasma Testosterone Levels
Baseline
|
0.76 mg/dL
Standard Deviation 0.57
|
2.72 mg/dL
Standard Deviation 1.13
|
|
Free Plasma Testosterone Levels
GnRH + Testosterone
|
1.34 mg/dL
Standard Deviation 0.23
|
2.19 mg/dL
Standard Deviation 0.19
|
PRIMARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of TestosteronePOST Lower body negative pressure Plasma renin activity
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Renal Response to LBNP
Baseline
|
1.05 ng/mL ANG/hour
Standard Deviation 0.82
|
1.10 ng/mL ANG/hour
Standard Deviation 0.46
|
|
Renal Response to LBNP
GnRH
|
0.54 ng/mL ANG/hour
Standard Deviation 0.33
|
1.14 ng/mL ANG/hour
Standard Deviation 1.31
|
|
Renal Response to LBNP
GnRH+Testosterone
|
0.83 ng/mL ANG/hour
Standard Deviation 0.71
|
1.36 ng/mL ANG/hour
Standard Deviation 1.51
|
PRIMARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of TestosteronePRE lower body negative pressure Plasma renin activity
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Renal Responses to LBNP
Baseline
|
0.53 ng/mL ANG/hour
Standard Deviation 0.48
|
0.85 ng/mL ANG/hour
Standard Deviation 0.97
|
|
Renal Responses to LBNP
GnRH
|
0.42 ng/mL ANG/hour
Standard Deviation 0.21
|
0.79 ng/mL ANG/hour
Standard Deviation 1.24
|
|
Renal Responses to LBNP
GnRH + Testosterone
|
0.63 ng/mL ANG/hour
Standard Deviation 0.43
|
0.76 ng/mL ANG/hour
Standard Deviation 0.75
|
PRIMARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of TestosteronePopulation: Systolic Blood Pressure
Blood pressure prior to lower body negative pressure
Outcome measures
| Measure |
Healthy Control
n=9 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=7 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Resting Systolic Blood Pressure
Baseline
|
128 mm Hg
Standard Deviation 15
|
123 mm Hg
Standard Deviation 13
|
|
Resting Systolic Blood Pressure
GnRH
|
131 mm Hg
Standard Deviation 10
|
124 mm Hg
Standard Deviation 16
|
|
Resting Systolic Blood Pressure
GnRH +Testosterone
|
130 mm Hg
Standard Deviation 12
|
121 mm Hg
Standard Deviation 16
|
PRIMARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of TestosteroneSBP at the end of lower body negative pressure
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Final Systolic Blood Pressure
Baseline
|
105 mm Hg
Standard Deviation 21
|
99 mm Hg
Standard Deviation 23
|
|
Final Systolic Blood Pressure
GnRH
|
109 mm Hg
Standard Deviation 16
|
113 mm Hg
Standard Deviation 12
|
|
Final Systolic Blood Pressure
GnRH + Testosterone
|
117 mm Hg
Standard Deviation 16
|
121 mm Hg
Standard Deviation 10
|
PRIMARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of TestosteroneTotal sympathetic nerve activity
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Resting Sympathetic Activity
Baseline
|
14.4 burst/100 heart beats
Standard Deviation 4.4
|
10.3 burst/100 heart beats
Standard Deviation 2.0
|
|
Resting Sympathetic Activity
GnRH
|
7.9 burst/100 heart beats
Standard Deviation 0.8
|
6.9 burst/100 heart beats
Standard Deviation 1.5
|
|
Resting Sympathetic Activity
GnRH + Testosterone
|
13.4 burst/100 heart beats
Standard Deviation 3.6
|
14.5 burst/100 heart beats
Standard Deviation 5.0
|
PRIMARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosteronemicroneurography, 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).
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Sympathetic Baroreflex
Baseline
|
-0.479 Gain (bursts/100 heart beats/ mm Hg)
Standard Deviation 0.085
|
-0.496 Gain (bursts/100 heart beats/ mm Hg)
Standard Deviation 0.142
|
|
Sympathetic Baroreflex
GnRH
|
-0.468 Gain (bursts/100 heart beats/ mm Hg)
Standard Deviation 0.101
|
-0.640 Gain (bursts/100 heart beats/ mm Hg)
Standard Deviation 0.171
|
|
Sympathetic Baroreflex
GnRH+Testosterone
|
-0.445 Gain (bursts/100 heart beats/ mm Hg)
Standard Deviation 0.087
|
-0.487 Gain (bursts/100 heart beats/ mm Hg)
Standard Deviation 0.124
|
SECONDARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of TestosteronePlasma aldosterone concentration
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Aldosterone
Baseline
|
75.7 pg/mL
Standard Deviation 41.4
|
136.5 pg/mL
Standard Deviation 60.1
|
|
Aldosterone
GnRH
|
44.0 pg/mL
Standard Deviation 37.0
|
127.8 pg/mL
Standard Deviation 70.5
|
|
Aldosterone
GnRH+testosterone
|
46.1 pg/mL
Standard Deviation 28.6
|
98.7 pg/mL
Standard Deviation 46.6
|
SECONDARY outcome
Timeframe: Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of TestosteroneP\[ACE\], angiotensin-converting enzyme
Outcome measures
| Measure |
Healthy Control
n=7 Participants
Healthy Control
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=9 Participants
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Renal Responses
Baseline
|
38.2 µg/L
Standard Deviation 14.7
|
101.9 µg/L
Standard Deviation 93.4
|
|
Renal Responses
GnRH
|
43.4 µg/L
Standard Deviation 27.3
|
77.7 µg/L
Standard Deviation 76.5
|
|
Renal Responses
GnRH + Testosterone
|
40.6 µg/L
Standard Deviation 14.1
|
44.2 µg/L
Standard Deviation 43.2
|
Adverse Events
Healthy Control
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
AE-PCOS
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Healthy Control
n=14 participants at risk
Healthy control participants.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
AE-PCOS
n=14 participants at risk
Participants with AE-PCOS.
GnRH antagonist: GnRH antagonist up to 16 days.
GnRH antagonist + MethylTESTOSTERone 5 MG: GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
non serious adverse event
|
7.1%
1/14 • Number of events 1 • Six to eight weeks
One subject experienced mild back pain during LBNP. Another experienced an incident of lupus on an experimental day, not due to our studies. However this was reported to our IRB.
|
0.00%
0/14 • Six to eight weeks
One subject experienced mild back pain during LBNP. Another experienced an incident of lupus on an experimental day, not due to our studies. However this was reported to our IRB.
|
|
Immune system disorders
non serious adverse event
|
0.00%
0/14 • Six to eight weeks
One subject experienced mild back pain during LBNP. Another experienced an incident of lupus on an experimental day, not due to our studies. However this was reported to our IRB.
|
7.1%
1/14 • Six to eight weeks
One subject experienced mild back pain during LBNP. Another experienced an incident of lupus on an experimental day, not due to our studies. However this was reported to our IRB.
|
Additional Information
Nina Stachenfeld
John B. Pierce Laboratory/Yale School of Medicine
Phone: 203 562 9901
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place