Cardiovascular Risk FactorNCT03236545
Menopause Effects on Vascular Function
A study testing No to Low Endogenous Estrogen and Estradiol in people with Cardiovascular Risk Factor, run by University of Delaware at 1 site in United States.
Trial summary
The purpose of the study is to identify the independent effect of estradiol (E2) on endothelin-1 (ET-1) mediated vasomotor function in women. The study is the first step in recognizing the impact of ovarian hormones on the mechanisms that regulate vascular function in women to provide a better understanding of the… Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Risk Factor
- What is being tested?
- No to Low Endogenous Estrogen and Estradiol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2016to 1 Nov 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Young women between 18-35 years of age with regular menstrual cycles
- Postmenopausal women between 50-65 years of age and no more than 10 years past menopause
- Non-smoking
- BMI < 30 kg/m2
- Free from known disease (heart disease, cancer, diabetes)
Who cannot join
- Current use of hormone therapy or within the past year
- Women using Depo-provera or an intra-uterine device (IUD)
- Pregnant, are planning on becoming pregnant, or are breast- feeding.
- History of stable or unstable angina
- Diabetes
- Neurological disease
Show all 16Show fewer
- Lung disease
- Kidney or liver disease
- Cancer
- Hysterectomy
- Peripheral vascular disease
- History of blood clots
- Heart disease
- Fibroids
- High blood pressure
- Stroke
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mechanisms of Vascular Dysfunction in Women: Role of Estradiol
The purpose of the study is to identify the independent effect of estradiol (E2) on endothelin-1 (ET-1) mediated vasomotor function in women. The study is the first step in recognizing the impact of ovarian hormones on the mechanisms that regulate vascular function in women to provide a better understanding of the cardiovascular efficacy of hormone therapy.
Read the detailed description
Cardiovascular disease (CVD) is the leading cause of death in women (Roger, Go, Lloyd, Adams, Berry, Brown, et al, 2011). Functional changes in the microvasculature occur with aging and precede atherosclerosis, contributing to CVD (Seals, Jablonski, \& Donato, 2011). Furthermore, because of the decline in ovarian hormones during menopause, age-related impairments in endothelial function are exacerbated in postmenopausal women (PMW). However, the safety and efficacy of currently available hormone-based therapies remains controversial (Devi, Sugiguchi, Pederson, Abrassart Glodowski, \& Nachtigall, 2013: Miller, Black, Brinton, Budoff, Cedars, Hodis, et al, 2009). Endothelin-1 (ET-1) is a potent vasoconstrictor produced and released by endothelial cells and implicated in the development of atherosclerosis (Best, McKenna, Holmes, \& Lerman, 1999; Donato, Gano, Eskurza, Silver, Gates, Jablonski, et al, 2009; Ihling, Szombathy, Bohrmann, Brockhaus, Schaefer, \& Loeffler, 2009). ET-1 binds to two receptor subtypes, ET-A and ET-B (Yanagisawa, Kurihara, Kimura, Tomobe, Kobayashi, Mitsui, et al, 1988). While both receptors are located on vascular smooth muscle (VSM) and cause vasoconstriction, ET-B receptors are also located on the endothelium and cause vasodilation (Gomez-Sanchez, Cozza, Foecking, Chiou, \& Ferris, 1990; Haynes, 1995; Ishikawa, Ihara, Noguchi, Mase, Mino Saeki, et al, 1994). In women, ET-1 preferentially binds to ET-B receptors compared to ET-A receptors, supporting findings of sex differences in ET-1 receptor responses and suggesting ET-B receptors are under hormonal control (Ergul, Shoemaker, Puett, \& Tackett, 1998; Kellogg, Liu, \& Pergola, 2001; Stauffer, Westby, Greiner, Van Guilder, \& Desouza, 2010). In animal models, estradiol (E2) reduces ET-1 mediated vasoconstriction and increases ET-B receptor mRNA (Pederson, Nielsen, Mortensen, Nilas, \& Ottesen, 2008). Thus, low levels of E2 in PMW may contribute to impaired vascular function through an ET-B receptor mechanism. However, the interaction between E2 and ET-1 receptor responses on regulating vascular function in women is currently unknown.
The long-term goal of the laboratory is to understand the impact of ovarian hormones on the mechanisms that regulate vascular function in women to provide a better understanding of the cardiovascular efficacy of hormone therapy. The study is the first step in reaching our goal; the objective of the study is to identify the independent effect of E2 on ET-1 mediated vasomotor function in women. The investigators will measure blood flow responses to local heating in the cutaneous circulation during perfusion of ET-1 receptor antagonists via microdialysis, coupled with measures of intracellular protein and receptor expression on endothelial cells and skin punch biopsies (to assess VSM cells) collected from young and PMW while controlling ovarian hormone exposure. Young women will be tested after suppressing ovarian production of E2 and progesterone with a gonadotropin-releasing hormone antagonist (GnRHant), and again after E2 administration; PMW, who are not using hormone therapy, will be tested before and after E2 admin. The central hypothesis is that declines in E2 impair microvascular vasodilatory function due to cellular changes in ET-B receptor expression on endothelial and VSM cells, and that E2 administration reverses these responses.
- Conditions
- Cardiovascular Risk Factor
- Being tested
- No to Low Endogenous Estrogen, Estradiol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No to Low Endogenous EstrogenOther
Ganirelix acetate (Antagon) will be used to prevent endogenous production of ovarian hormones in young women. Ganirelix is derived from native GnRH, and acts by competitively blocking GnRH receptors on the pituitary and subsequent pathways. Thus, administration of the GnRH antagonist (GnRHant) suppresses steroidogenesis, leading to low or undetectable serum estrogen and progesterone concentrations, which occurs within two days of initiation of administration (Oberye, Mannaerts, Huisman \& Timmer, 1999; Oberye, Mannaerts, Kleijn, \& Timmer, 1999).
EstradiolOther
Also called Vivelle dot
Short term estradiol administration elicits changes in vascular function in women, and 0.1mg/day patch is the upper recommended limit for hormone therapy in women (Wenner, Taylor, \& Stachenfeld, 2011; Moreau, Hildreth, Meditz, Deane \& Kohrt, 2012).
| Study group | Role | What they receive |
|---|---|---|
| No to Low Endogenous Estrogen | Experimental | PMW and young women (YW) will receive medical study clearance after a detailed physical examination. YW will self-administer subcutaneous injections of the gonadotropin-releasing hormone (GnRH) antagonist, ganirelix acetate (Antagon, 0.25 mg/day in 0.5 ml of normal saline, Organon, Inc., West Orange, New Jersey,) daily to suppress endogenous ovarian hormone production (16, 17, 18). This will begin following a separate medical screening at Reproductive Associates of Delaware 48 hours prior to initiating the hormone intervention to rule out other contraindications prior to beginning the treatment. YW will begin using the antagonist on days 26-28 of their menstrual cycle, and continue daily for 10-12 days. The experimental protocol will be conducted in YW after 3-4 days of using the GnRH antagonist. PMW will complete the experimental protocol prior to use of the 17β-estradiol (E2, 0.1 mg/day patch, Vivelle dot; estradiol patch). Receives: Other: No to Low Endogenous Estrogen |
| Estrogen Add-Back | Experimental | Estradiol (E2, 0.1 mg/day patch, Vivelle dot; estradiol patch) will be administered for 7 days to both young and PMW. Young women will use the E2 over the last 7 days of Antagon administration. Receives: Other: No to Low Endogenous Estrogen; Other: Estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vascular endothelial function
The capacity of the small and large blood vessels to dilate.
Measured: 3 years
Secondary outcomes (1)
Endothelin receptor expression
Venous endothelial cells and skin punch biopsy will be collected and stained for ET-A and ET-B receptor expression
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2017
- Study start1 Jul 2016
- Primary completion30 Apr 2022
- Study completion1 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular Risk FactorStudies of the same condition, open and under way.
- 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
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Delaware
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Principal investigator, Megan M. Wenner, University of Delaware
- Investigators
- Megan Wenner, PhD, Principal investigator, University of Delaware
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03236545
- Sponsor's protocol ID
- 385453-18
- Status last verified
- Nov 2022
- First submitted
- 28 Jul 2017
- Last updated
- 14 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Information will be available through clinicaltrials.gov database within one year of completion of study.
Publications
Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011 Feb 1;123(4):e18-e209. doi: 10.1161/CIR.0b013e3182009701. Epub 2010 Dec 15.
PubMed 21160056Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (Lond). 2011 May;120(9):357-75. doi: 10.1042/CS20100476.
PubMed 21244363Devi G, Sugiguchi F, Pedersen AT, Abrassart D, Glodowski M, Nachtigall L. Current attitudes on self-use and prescription of hormone therapy among New York City gynaecologists. Menopause Int. 2013 Sep;19(3):121-6. doi: 10.1177/1754045313478941. Epub 2013 May 21.
PubMed 23761315Miller VM, Black DM, Brinton EA, Budoff MJ, Cedars MI, Hodis HN, Lobo RA, Manson JE, Merriam GR, Naftolin F, Santoro N, Taylor HS, Harman SM. Using basic science to design a clinical trial: baseline characteristics of women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). J Cardiovasc Transl Res. 2009 Sep;2(3):228-39. doi: 10.1007/s12265-009-9104-y. Epub 2009 May 22.
PubMed 19668346Best PJ, McKenna CJ, Hasdai D, Holmes DR Jr, Lerman A. Chronic endothelin receptor antagonism preserves coronary endothelial function in experimental hypercholesterolemia. Circulation. 1999 Apr 6;99(13):1747-52. doi: 10.1161/01.cir.99.13.1747.
PubMed 10190886Donato AJ, Gano LB, Eskurza I, Silver AE, Gates PE, Jablonski K, Seals DR. Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H425-32. doi: 10.1152/ajpheart.00689.2008. Epub 2009 May 22.
PubMed 19465546Ihling C, Szombathy T, Bohrmann B, Brockhaus M, Schaefer HE, Loeffler BM. Coexpression of endothelin-converting enzyme-1 and endothelin-1 in different stages of human atherosclerosis. Circulation. 2001 Aug 21;104(8):864-9. doi: 10.1161/hc3301.094742.
PubMed 11514370Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411-5. doi: 10.1038/332411a0.
PubMed 2451132Gomez-Sanchez CE, Cozza EN, Foecking MF, Chiou S, Ferris MW. Endothelin receptor subtypes and stimulation of aldosterone secretion. Hypertension. 1990 Jun;15(6 Pt 2):744-7. doi: 10.1161/01.hyp.15.6.744.
PubMed 2161792Haynes WG. Endothelins as regulators of vascular tone in man. Clin Sci (Lond). 1995 May;88(5):509-17. doi: 10.1042/cs0880509.
PubMed 7614809Ishikawa K, Ihara M, Noguchi K, Mase T, Mino N, Saeki T, Fukuroda T, Fukami T, Ozaki S, Nagase T, et al. Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4892-6. doi: 10.1073/pnas.91.11.4892.
PubMed 8197152Ergul A, Shoemaker K, Puett D, Tackett RL. Gender differences in the expression of endothelin receptors in human saphenous veins in vitro. J Pharmacol Exp Ther. 1998 May;285(2):511-7.
PubMed 9580591Kellogg DL Jr, Liu Y, Pergola PE. Selected contribution: Gender differences in the endothelin-B receptor contribution to basal cutaneous vascular tone in humans. J Appl Physiol (1985). 2001 Nov;91(5):2407-11; discussion 2389-90. doi: 10.1152/jappl.2001.91.5.2407.
PubMed 11641388Stauffer BL, Westby CM, Greiner JJ, Van Guilder GP, Desouza CA. Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults. Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R261-5. doi: 10.1152/ajpregu.00626.2009. Epub 2009 Nov 25.
PubMed 19939973Pedersen SH, Nielsen LB, Mortensen A, Nilas L, Ottesen B. Progestins oppose the effects of estradiol on the endothelin-1 receptor type B in coronary arteries from ovariectomized hyperlipidemic rabbits. Menopause. 2008 May-Jun;15(3):503-10. doi: 10.1097/gme.0b013e318156f803.
PubMed 18188139
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Vascular Dysfunction in Women: Role of Estradiol
- ClinicalTrials.gov ID
- NCT03236545
- Acronym / sponsor ID
- 385453-18
- Conditions
- Cardiovascular Risk Factor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of DelawareUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- 1 Jul 2016 (actual)
- Primary completion
- 30 Apr 2022 (actual)
- Study completion
- 1 Nov 2022 (actual)
- First posted
- 2 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to identify the independent effect of estradiol (E2) on endothelin-1 (ET-1) mediated vasomotor function in women. The study is the first step in recognizing the impact of ovarian hormones on the mechanisms that regulate vascular function in women to provide a better understanding of the cardiovascular efficacy of hormone therapy.
Detailed description
Cardiovascular disease (CVD) is the leading cause of death in women (Roger, Go, Lloyd, Adams, Berry, Brown, et al, 2011). Functional changes in the microvasculature occur with aging and precede atherosclerosis, contributing to CVD (Seals, Jablonski, \& Donato, 2011). Furthermore, because of the decline in ovarian hormones during menopause, age-related impairments in endothelial function are exacerbated in postmenopausal women (PMW). However, the safety and efficacy of currently available hormone-based therapies remains controversial (Devi, Sugiguchi, Pederson, Abrassart Glodowski, \& Nachtigall, 2013: Miller, Black, Brinton, Budoff, Cedars, Hodis, et al, 2009). Endothelin-1 (ET-1) is a potent vasoconstrictor produced and released by endothelial cells and implicated in the development of atherosclerosis (Best, McKenna, Holmes, \& Lerman, 1999; Donato, Gano, Eskurza, Silver, Gates, Jablonski, et al, 2009; Ihling, Szombathy, Bohrmann, Brockhaus, Schaefer, \& Loeffler, 2009). ET-1 binds to two receptor subtypes, ET-A and ET-B (Yanagisawa, Kurihara, Kimura, Tomobe, Kobayashi, Mitsui, et al, 1988). While both receptors are located on vascular smooth muscle (VSM) and cause vasoconstriction, ET-B receptors are also located on the endothelium and cause vasodilation (Gomez-Sanchez, Cozza, Foecking, Chiou, \& Ferris, 1990; Haynes, 1995; Ishikawa, Ihara, Noguchi, Mase, Mino Saeki, et al, 1994). In women, ET-1 preferentially binds to ET-B receptors compared to ET-A receptors, supporting findings of sex differences in ET-1 receptor responses and suggesting ET-B receptors are under hormonal control (Ergul, Shoemaker, Puett, \& Tackett, 1998; Kellogg, Liu, \& Pergola, 2001; Stauffer, Westby, Greiner, Van Guilder, \& Desouza, 2010). In animal models, estradiol (E2) reduces ET-1 mediated vasoconstriction and increases ET-B receptor mRNA (Pederson, Nielsen, Mortensen, Nilas, \& Ottesen, 2008). Thus, low levels of E2 in PMW may contribute to impaired vascular function through an ET-B receptor mechanism. However, the interaction between E2 and ET-1 receptor responses on regulating vascular function in women is currently unknown.
The long-term goal of the laboratory is to understand the impact of ovarian hormones on the mechanisms that regulate vascular function in women to provide a better understanding of the cardiovascular efficacy of hormone therapy. The study is the first step in reaching our goal; the objective of the study is to identify the independent effect of E2 on ET-1 mediated vasomotor function in women. The investigators will measure blood flow responses to local heating in the cutaneous circulation during perfusion of ET-1 receptor antagonists via microdialysis, coupled with measures of intracellular protein and receptor expression on endothelial cells and skin punch biopsies (to assess VSM cells) collected from young and PMW while controlling ovarian hormone exposure. Young women will be tested after suppressing ovarian production of E2 and progesterone with a gonadotropin-releasing hormone antagonist (GnRHant), and again after E2 administration; PMW, who are not using hormone therapy, will be tested before and after E2 admin. The central hypothesis is that declines in E2 impair microvascular vasodilatory function due to cellular changes in ET-B receptor expression on endothelial and VSM cells, and that E2 administration reverses these responses.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No to Low Endogenous Estrogen | Experimental | Other: No to Low Endogenous EstrogenPMW and young women (YW) will receive medical study clearance after a detailed physical examination. YW will self-administer subcutaneous injections of the gonadotropin-releasing hormone (GnRH) antagonist, ganirelix acetate (Antagon, 0.25 mg/day in 0.5 ml of normal saline, Organon, Inc., West Orange, New Jersey,) daily to suppress endogenous ovarian hormone production (16, 17, 18). This will begin following a separate medical screening at Reproductive Associates of Delaware 48 hours prior to initiating the hormone intervention to rule out other contraindications prior to beginning the treatment. YW will begin using the antagonist on days 26-28 of their menstrual cycle, and continue daily for 10-12 days. The experimental protocol will be conducted in YW after 3-4 days of using the GnRH antagonist. PMW will complete the experimental protocol prior to use of the 17β-estradiol (E2, 0.1 mg/day patch, Vivelle dot; estradiol patch). |
| Estrogen Add-Back | Experimental | Other: No to Low Endogenous Estrogen, Other: EstradiolEstradiol (E2, 0.1 mg/day patch, Vivelle dot; estradiol patch) will be administered for 7 days to both young and PMW. Young women will use the E2 over the last 7 days of Antagon administration. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Young women between 18-35 years of age with regular menstrual cycles
- Postmenopausal women between 50-65 years of age and no more than 10 years past menopause
- Non-smoking
- BMI < 30 kg/m2
- Free from known disease (heart disease, cancer, diabetes)
Key exclusion criteria (16 listed)
- Current use of hormone therapy or within the past year
- Women using Depo-provera or an intra-uterine device (IUD)
- Pregnant, are planning on becoming pregnant, or are breast- feeding.
- History of stable or unstable angina
- Diabetes
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 |
|---|---|---|
| No to Low Endogenous EstrogenGanirelix acetate (Antagon) will be used to prevent endogenous production of ovarian hormones in young women. Ganirelix is derived from native GnRH, and acts by competitively blocking GnRH receptors on the pituitary and subsequent pathways. Thus, administration of the GnRH antagonist (GnRHant) suppresses steroidogenesis, leading to low or undetectable serum estrogen and progesterone concentrations, which occurs within two days of initiation of administration (Oberye, Mannaerts, Huisman \& Timmer, 1999; Oberye, Mannaerts, Kleijn, \& Timmer, 1999). | Other | Estrogen Add-Back, No to Low Endogenous Estrogen |
| EstradiolAlso: Vivelle dotShort term estradiol administration elicits changes in vascular function in women, and 0.1mg/day patch is the upper recommended limit for hormone therapy in women (Wenner, Taylor, \& Stachenfeld, 2011; Moreau, Hildreth, Meditz, Deane \& Kohrt, 2012). | Other | Estrogen Add-Back |
Primary outcome
Vascular endothelial function
Time frame: 3 years
The capacity of the small and large blood vessels to dilate.
1 secondary outcome
Endothelin receptor expression
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2022.
- Background: PubMed 21160056Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011 Feb 1;123(4):e18-e209. doi: 10.1161/CIR.0b013e3182009701. Epub 2010 Dec 15.
- Background: PubMed 21244363Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (Lond). 2011 May;120(9):357-75. doi: 10.1042/CS20100476.
- Background: PubMed 23761315Devi G, Sugiguchi F, Pedersen AT, Abrassart D, Glodowski M, Nachtigall L. Current attitudes on self-use and prescription of hormone therapy among New York City gynaecologists. Menopause Int. 2013 Sep;19(3):121-6. doi: 10.1177/1754045313478941. Epub 2013 May 21.
- Background: PubMed 19668346Miller VM, Black DM, Brinton EA, Budoff MJ, Cedars MI, Hodis HN, Lobo RA, Manson JE, Merriam GR, Naftolin F, Santoro N, Taylor HS, Harman SM. Using basic science to design a clinical trial: baseline characteristics of women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). J Cardiovasc Transl Res. 2009 Sep;2(3):228-39. doi: 10.1007/s12265-009-9104-y. Epub 2009 May 22.
- Background: PubMed 10190886Best PJ, McKenna CJ, Hasdai D, Holmes DR Jr, Lerman A. Chronic endothelin receptor antagonism preserves coronary endothelial function in experimental hypercholesterolemia. Circulation. 1999 Apr 6;99(13):1747-52. doi: 10.1161/01.cir.99.13.1747.
- Background: PubMed 19465546Donato AJ, Gano LB, Eskurza I, Silver AE, Gates PE, Jablonski K, Seals DR. Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H425-32. doi: 10.1152/ajpheart.00689.2008. Epub 2009 May 22.
- Background: PubMed 11514370Ihling C, Szombathy T, Bohrmann B, Brockhaus M, Schaefer HE, Loeffler BM. Coexpression of endothelin-converting enzyme-1 and endothelin-1 in different stages of human atherosclerosis. Circulation. 2001 Aug 21;104(8):864-9. doi: 10.1161/hc3301.094742.
- Background: PubMed 2451132Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411-5. doi: 10.1038/332411a0.
- Background: PubMed 2161792Gomez-Sanchez CE, Cozza EN, Foecking MF, Chiou S, Ferris MW. Endothelin receptor subtypes and stimulation of aldosterone secretion. Hypertension. 1990 Jun;15(6 Pt 2):744-7. doi: 10.1161/01.hyp.15.6.744.
- Background: PubMed 7614809Haynes WG. Endothelins as regulators of vascular tone in man. Clin Sci (Lond). 1995 May;88(5):509-17. doi: 10.1042/cs0880509.
- Background: PubMed 8197152Ishikawa K, Ihara M, Noguchi K, Mase T, Mino N, Saeki T, Fukuroda T, Fukami T, Ozaki S, Nagase T, et al. Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4892-6. doi: 10.1073/pnas.91.11.4892.
- Background: PubMed 9580591Ergul A, Shoemaker K, Puett D, Tackett RL. Gender differences in the expression of endothelin receptors in human saphenous veins in vitro. J Pharmacol Exp Ther. 1998 May;285(2):511-7.
- Individual participant dataSharing planned: Yes. Information will be available through clinicaltrials.gov database within one year of completion of 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.
Megan Wenner, PhD principal investigator
University of Delaware
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing No to Low Endogenous Estrogen and Estradiol in people with Cardiovascular Risk Factor, run by University of Delaware at 1 site in United States.
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 16 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: finished, as of the sponsor's last update on 14 Nov 2022. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Vascular endothelial function (time frame: 3 years). 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 NCT03236545, which also lists 22 linked publications.
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 14 Nov 2022.