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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL135089-01A1 | U.S. NIH Grant/Contract | View source |
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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.
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Women with androgen excess polycystic ovary syndrome (AE-PCOS) leads to hypertension.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Control | Active Comparator | Healthy control participants. |
|
| AE-PCOS | Experimental | Participants with AE-PCOS. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GnRH antagonist | Drug | GnRH antagonist up to 16 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Aldosterone | Plasma aldosterone concentration | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
| Renal Responses | P[ACE], angiotensin-converting enzyme |
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Inclusion Criteria:
Controls:
-Diagnosis of Insulin resistance
Exclusion Criteria:
Obese Insulin Resistant (IR) women
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| Name | Affiliation | Role |
|---|---|---|
| Nina Stachenfeld, PhD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The John B Pierce Laboratory | New Haven | Connecticut | 06519 | United States |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline characteristics are presented for people that completed the study- which is defined as those that were allocated, began and completed the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | AE-PCOS |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Posted | Mean | Standard Deviation | Arbitrary Units/Beat/mmHg | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| non serious adverse event | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nina Stachenfeld | John B. Pierce Laboratory/Yale School of Medicine | 203 562 9901 | 219 | nina.stachenfeld@yale.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 13, 2022 | Feb 24, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 14, 2021 | Feb 24, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 |
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| ID | Term |
|---|---|
| C092464 | LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)- |
| C061018 | ganirelix |
| D008777 | Methyltestosterone |
| ID | Term |
|---|---|
| D013739 | Testosterone |
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
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| GnRH antagonist + MethylTESTOSTERone 5 MG | Drug | GnRH antagonist + MethylTESTOSTERone 5 MG up to 5 days. |
|
|
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 |
| Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
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.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | 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.
|
|
|
| Primary | Free Plasma Testosterone Levels | Concentration of testosterone in blood. | Posted | Mean | Standard Deviation | mg/dL | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
|
| Primary | Renal Response to LBNP | POST Lower body negative pressure Plasma renin activity | Posted | Mean | Standard Deviation | ng/mL ANG/hour | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
| Primary | Renal Responses to LBNP | PRE lower body negative pressure Plasma renin activity | Posted | Mean | Standard Deviation | ng/mL ANG/hour | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
| Primary | Resting Systolic Blood Pressure | Blood pressure prior to lower body negative pressure | Systolic Blood Pressure | Posted | Mean | Standard Deviation | mm Hg | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
|
| Primary | Final Systolic Blood Pressure | SBP at the end of lower body negative pressure | Posted | Mean | Standard Deviation | mm Hg | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
| Primary | Resting Sympathetic Activity | Total sympathetic nerve activity | Posted | Mean | Standard Deviation | burst/100 heart beats | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
|
| Primary | 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). | Posted | Mean | Standard Deviation | Gain (bursts/100 heart beats/ mm Hg) | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
|
| Secondary | Aldosterone | Plasma aldosterone concentration | Posted | Mean | Standard Deviation | pg/mL | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
|
| Secondary | Renal Responses | P[ACE], angiotensin-converting enzyme | Posted | Mean | Standard Deviation | µg/L | Baseline, assessed at 7 days of GnRH, assessed at 16 days GnRH+ 5 days of Testosterone |
|
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 1 |
| 14 |
| EG001 | 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. | 0 | 14 | 0 | 14 | 1 | 14 |
| non serious adverse event | Immune system disorders | Non-systematic Assessment | lupus flair unrelated to study |
|
Not provided
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| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| GnRH + Testosterone |
|
| Equivalence |
We compared across groups and within groups over time. |
| GnRH+Testosterone |
|
| GnRH + Testosterone |
|
| GnRH +Testosterone |
|
| GnRH + Testosterone |
|
| GnRH + Testosterone |
|
| Other |
| GnRH+Testosterone |
|
| GnRH+testosterone |
|
| GnRH + Testosterone |
|