Cardiovascular DiseasesPhase 4NCT03371823
Vascular Dysfunction in Hypertensive Postmenopausal Women
A Phase 4 study testing Normotensive and Hypertensives in people with Cardiovascular Diseases and Hypertension, run by University of Delaware at 1 site in United States.
Trial summary
The purpose of this study is to investigate the role of ET-1 in mediating vasoconstrictor tone in hypertensive postmenopausal women (PMW) alone and in combination with a commonly prescribed Angiotensin II (ANG II) antagonist. The long term goal is to understand the mechanisms contributing to hypertension (HTN) in PMW. Read more about this study
- Who is it for?
- Ages 50 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Hypertension
- What is being tested?
- Normotensive and Hypertensives
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2017to 31 Dec 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- > 1year post menopausal.
- Age range 50-70 years
- Resting ECG in normal limits
- Standard blood chemistry within normal limits
- Systolic blood pressure: <130mm Hg for normotensives; >130mm Hg for hypertensives.
- Diastolic blood pressure: < 80mm Hg for normotensives; > 80mm Hg for hypertensives.
Who cannot join
- History of cardiovascular disease
- Blood clots or stroke
- Cancer
- Diabetes
- Kidney or Liver disease
- Obesity (BMI>35kg/m2)
Show all 11Show fewer
- Pregnant/Breast feeding
- Current use of hormone therapy
- Current use of tobacco products
- High cholesterol
- Current use of anti-hypertensive meds
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Losartan and ET-1 Mediated Constriction in Postmenopausal Women With High Blood Pressure
The purpose of this study is to investigate the role of ET-1 in mediating vasoconstrictor tone in hypertensive postmenopausal women (PMW) alone and in combination with a commonly prescribed Angiotensin II (ANG II) antagonist. The long term goal is to understand the mechanisms contributing to hypertension (HTN) in PMW. This study is the first step in reaching our goal.
Read the detailed description
Cardiovascular disease (CVD) is the leading cause of death in women, and mortality from CVD is higher in PMW compared to age-matched men. PMW are at a greater risk for developing HTN, a major risk factor for CVD. They are also more likely to have uncontrolled or resistant HTN despite medication.
ANG II is a common therapeutic target for the treatment HTN. ANG II blockade is highly effective in normalizing blood pressure (BP) in hypertensive male rats, but does not reduce BP to the same degree in hypertensive post menopausal female rats. Endothelin-1 (ET-1) receptor antagonists reduce BP in hypertensive postmenopausal female rats, but have no effect on males. Thus the mechanisms contributing to HTN in female rats and likely women, particularly after menopause, are complex, multifactorial and not completely understood.
After menopause, the vasoconstrictor effects of both ANG II and ET-1 are amplified in animal models. As such, these two predominant pathways may contribute to the high incidence of HTN in PMW. ET-1 is a potent vasoconstrictor produced and released by endothelial cells that binds to two receptor subtypes, ET-A and ET-B. While both receptors are located on vascular smooth muscle (VSM) and mediate vasoconstriction, ET-B receptors are also located on the endothelium and mediate vasodilation via nitric oxide.
Importantly, the production of ET-1 and expression of ET-A and B receptors can be modulated by hormones such as estradiol and ANG II. Estradiol attenuates ET-1 production, and reduces ET-1 mediated vasoconstriction via an ET-B receptor mechanism in vitro. Thus, decline in estradiol after menopause may enhance vasoconstrictor tone via ET-1 and lead to HTN. ET-1 also potentiates the vasoconstrictor effects of ANG II since the vasoconstrictor and hypertensive effects of ANG II are ameliorated by ET-1 receptor blockade. Additionally, ANG II stimulates the synthesis of ET-1 and upregulates ET-A and ET-B receptor expression on VSM. The ANG II receptor antagonist Losartan reduces ET-A and ET-B receptor expression and attenuates the constrictor effects of ET-1 in a diabetic rat model. Therefore, ET-1 is an important independent factor contributing to HTN in PMW, but therapeutic agents targeting both ANG II and ET-1 may have greater efficacy given their interactions.
The investigators propose a comprehensive assessment of vascular function by measuring blood flow responses in the cutaneous circulation during perfusion of ET-1 receptor antagonists via microdialysis, combined with measures of intracellular protein and receptor expression of endothelial cells and skin punch biopsies collected from normotensive and hypertensive PMW. Investigators central hypothesis is that hypertensive PMW have greater ET-1 mediated vasoconstrictor tone due to increased ET-1 expression, down-regulation of ET-B receptors on endothelial cells and up-regulation of both ET-A and ET-B receptors on VSM leading to increased vasoconstriction and HTN. Investigators further hypothesize that ANG II exacerbates the increase in ET-1, and ET-A and ET-B receptor expression contributing to exaggerated constriction with HTN in PMW.
- Conditions
- Cardiovascular Diseases, Hypertension
- Being tested
- Normotensive, Hypertensives
- Keywords
- Hypertension, Endothelin-1 receptor
- Medical subject headings
- Cardiovascular Diseases, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NormotensiveOther
FMD is a measure of endothelial function by assessing the degree to which vessel dilates in response to increased flow. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection in all women. Laser Doppler flowmetry is used in combination with cutaneous microdialysis as a minimally invasive technique to examine mechanisms of vascular function. ET-B and ET-A receptor antagonists will be perfused via intradermal microdialysis fibers while measuring cutaneous blood flow. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will also be assessed. Immunohistochemistry will be performed on skin punch biopsy samples to assess for protein expression of ET-A and ET-B receptors.
HypertensivesDrug
ANG II increases the synthesis of ET-1 and alters ET-A/B receptor expression, thus affecting ET-1 bioavailability. Losartan is an ANG II receptor antagonist which attenuates ET-1 production. Losartan 50 mg daily is administered for 14 days to hypertensive women. FMD is used to measure endothelial function. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection. Laser Doppler flowmetry with cutaneous microdialysis is used to examine vascular function when ET-A and ET-B receptor antagonists is perfused via intradermal microdialysis fibers. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will be assessed. Skin punch biopsy samples will be used to assess for protein expression of ET-A and ET-B receptors.
| Study group | Role | What they receive |
|---|---|---|
| Normotensive | Other | Normotensive PMW will complete an experimental visit to assess vascular function. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visit to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. Receives: Other: Normotensive |
| Hypertensives | Experimental | Hypertensive women will be tested at baseline and then administered Losartan 50 mg once a day at night for 14 days. Vascular function is measured at baseline and again after 2 weeks of losartan. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visits to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. Receives: Drug: Hypertensives |
What is being measured
The primary outcome is the main question the study is designed to answer.
ET-1 Mediated Constriction
Cutaneous blood flow is measured via laser Doppler flowmetry during cutaneous microdialysis perfusions of ET-A and ET-B receptor antagonists as previously described by Wenner MM in 2017(see reference list).
Measured: Each participant was assessed at baseline and 2 weeks later.
Secondary outcomes (1)
Endothelin Receptor A and B Expression
ET-A and ET-B receptors will be examined using immunocytochemistry from 3mm skin punch biopsy in women pre/post losartan administration. This Secondary aim was not complete due to difficulty with enrollment (no data collected in these groups).
Measured: Baseline and 2 weeks later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2017
- Study start1 Sep 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Why it stopped: We experienced challenges recruiting unmedicated women with high blood pressure for the intervention.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies 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 4
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Delaware
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Megan M. Wenner, University of Delaware
- Investigators
- Megan Wenner, Ph.D, Principal investigator, University of Delaware
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03371823
- Sponsor's protocol ID
- 1009297
- Status last verified
- Jan 2022
- First submitted
- 22 Nov 2017
- Last updated
- 19 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation. 2013 Jan 1;127(1):143-52. doi: 10.1161/CIR.0b013e318282ab8f. No abstract available.
PubMed 23283859Barton M, Meyer MR. Postmenopausal hypertension: mechanisms and therapy. Hypertension. 2009 Jul;54(1):11-8. doi: 10.1161/HYPERTENSIONAHA.108.120022. Epub 2009 May 26. No abstract available.
PubMed 19470884Kim JK, Alley D, Seeman T, Karlamangla A, Crimmins E. Recent changes in cardiovascular risk factors among women and men. J Womens Health (Larchmt). 2006 Jul-Aug;15(6):734-46. doi: 10.1089/jwh.2006.15.734.
PubMed 16910905Yanes LL, Romero DG, Iles JW, Iliescu R, Gomez-Sanchez C, Reckelhoff JF. Sexual dimorphism in the renin-angiotensin system in aging spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2006 Aug;291(2):R383-90. doi: 10.1152/ajpregu.00510.2005. Epub 2006 Mar 30.
PubMed 16914423Yanes LL, Romero DG, Iliescu R, Zhang H, Davis D, Reckelhoff JF. Postmenopausal hypertension: role of the Renin-Angiotensin system. Hypertension. 2010 Sep;56(3):359-63. doi: 10.1161/HYPERTENSIONAHA.110.152975. Epub 2010 Aug 2.
PubMed 20679182Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension. 2001 May;37(5):1199-208. doi: 10.1161/01.hyp.37.5.1199.
PubMed 11358929Yanes LL, Reckelhoff JF. Postmenopausal hypertension. Am J Hypertens. 2011 Jul;24(7):740-9. doi: 10.1038/ajh.2011.71. Epub 2011 Apr 21.
PubMed 21509049Yanes LL, Romero DG, Cucchiarelli VE, Fortepiani LA, Gomez-Sanchez CE, Santacruz F, Reckelhoff JF. Role of endothelin in mediating postmenopausal hypertension in a rat model. Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R229-33. doi: 10.1152/ajpregu.00697.2003. Epub 2004 Aug 19.
PubMed 15319224Lima R, Yanes LL, Davis DD, Reckelhoff JF. Roles played by 20-HETE, angiotensin II and endothelin in mediating the hypertension in aging female spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2013 Feb;304(3):R248-51. doi: 10.1152/ajpregu.00380.2012. Epub 2012 Dec 5.
PubMed 23220478Haynes 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 8197152Yanagisawa 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 2451132Juan SH, Chen JJ, Chen CH, Lin H, Cheng CF, Liu JC, Hsieh MH, Chen YL, Chao HH, Chen TH, Chan P, Cheng TH. 17beta-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells. Am J Physiol Heart Circ Physiol. 2004 Sep;287(3):H1254-61. doi: 10.1152/ajpheart.00723.2003. Epub 2004 May 6.
PubMed 15130882Pedersen 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 18188139Wenzel RR, Ruthemann J, Bruck H, Schafers RF, Michel MC, Philipp T. Endothelin-A receptor antagonist inhibits angiotensin II and noradrenaline in man. Br J Clin Pharmacol. 2001 Aug;52(2):151-7. doi: 10.1046/j.0306-5251.2001.01422.x.
PubMed 11488771
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Losartan and ET-1 Mediated Constriction in Postmenopausal Women With High Blood Pressure
- ClinicalTrials.gov ID
- NCT03371823
- Acronym / sponsor ID
- 1009297
- Conditions
- Cardiovascular Diseases, Hypertension
- Keywords
- Hypertension, Endothelin-1 receptor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: We experienced challenges recruiting unmedicated women with high blood pressure for the intervention.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of DelawareUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 13 Dec 2017 (actual)
- Results
- Posted 19 Jan 2022
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 this study is to investigate the role of ET-1 in mediating vasoconstrictor tone in hypertensive postmenopausal women (PMW) alone and in combination with a commonly prescribed Angiotensin II (ANG II) antagonist. The long term goal is to understand the mechanisms contributing to hypertension (HTN) in PMW. This study is the first step in reaching our goal.
Detailed description
Cardiovascular disease (CVD) is the leading cause of death in women, and mortality from CVD is higher in PMW compared to age-matched men. PMW are at a greater risk for developing HTN, a major risk factor for CVD. They are also more likely to have uncontrolled or resistant HTN despite medication.
ANG II is a common therapeutic target for the treatment HTN. ANG II blockade is highly effective in normalizing blood pressure (BP) in hypertensive male rats, but does not reduce BP to the same degree in hypertensive post menopausal female rats. Endothelin-1 (ET-1) receptor antagonists reduce BP in hypertensive postmenopausal female rats, but have no effect on males. Thus the mechanisms contributing to HTN in female rats and likely women, particularly after menopause, are complex, multifactorial and not completely understood.
After menopause, the vasoconstrictor effects of both ANG II and ET-1 are amplified in animal models. As such, these two predominant pathways may contribute to the high incidence of HTN in PMW. ET-1 is a potent vasoconstrictor produced and released by endothelial cells that binds to two receptor subtypes, ET-A and ET-B. While both receptors are located on vascular smooth muscle (VSM) and mediate vasoconstriction, ET-B receptors are also located on the endothelium and mediate vasodilation via nitric oxide.
Importantly, the production of ET-1 and expression of ET-A and B receptors can be modulated by hormones such as estradiol and ANG II. Estradiol attenuates ET-1 production, and reduces ET-1 mediated vasoconstriction via an ET-B receptor mechanism in vitro. Thus, decline in estradiol after menopause may enhance vasoconstrictor tone via ET-1 and lead to HTN. ET-1 also potentiates the vasoconstrictor effects of ANG II since the vasoconstrictor and hypertensive effects of ANG II are ameliorated by ET-1 receptor blockade. Additionally, ANG II stimulates the synthesis of ET-1 and upregulates ET-A and ET-B receptor expression on VSM. The ANG II receptor antagonist Losartan reduces ET-A and ET-B receptor expression and attenuates the constrictor effects of ET-1 in a diabetic rat model. Therefore, ET-1 is an important independent factor contributing to HTN in PMW, but therapeutic agents targeting both ANG II and ET-1 may have greater efficacy given their interactions.
The investigators propose a comprehensive assessment of vascular function by measuring blood flow responses in the cutaneous circulation during perfusion of ET-1 receptor antagonists via microdialysis, combined with measures of intracellular protein and receptor expression of endothelial cells and skin punch biopsies collected from normotensive and hypertensive PMW. Investigators central hypothesis is that hypertensive PMW have greater ET-1 mediated vasoconstrictor tone due to increased ET-1 expression, down-regulation of ET-B receptors on endothelial cells and up-regulation of both ET-A and ET-B receptors on VSM leading to increased vasoconstriction and HTN. Investigators further hypothesize that ANG II exacerbates the increase in ET-1, and ET-A and ET-B receptor expression contributing to exaggerated constriction with HTN in PMW.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normotensive | Other | Other: NormotensiveNormotensive PMW will complete an experimental visit to assess vascular function. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visit to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. |
| Hypertensives | Experimental | Drug: HypertensivesHypertensive women will be tested at baseline and then administered Losartan 50 mg once a day at night for 14 days. Vascular function is measured at baseline and again after 2 weeks of losartan. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visits to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- > 1year post menopausal.
- Age range 50-70 years
- Resting ECG in normal limits
- Standard blood chemistry within normal limits
- Systolic blood pressure: <130mm Hg for normotensives; >130mm Hg for hypertensives.
Key exclusion criteria (11 listed)
- History of cardiovascular disease
- Blood clots or stroke
- Cancer
- Diabetes
- Kidney or Liver disease
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 |
|---|---|---|
| NormotensiveFMD is a measure of endothelial function by assessing the degree to which vessel dilates in response to increased flow. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection in all women. Laser Doppler flowmetry is used in combination with cutaneous microdialysis as a minimally invasive technique to examine mechanisms of vascular function. ET-B and ET-A receptor antagonists will be perfused via intradermal microdialysis fibers while measuring cutaneous blood flow. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will also be assessed. Immunohistochemistry will be performed on skin punch biopsy samples to assess for protein expression of ET-A and ET-B receptors. | Other | Normotensive |
| HypertensivesANG II increases the synthesis of ET-1 and alters ET-A/B receptor expression, thus affecting ET-1 bioavailability. Losartan is an ANG II receptor antagonist which attenuates ET-1 production. Losartan 50 mg daily is administered for 14 days to hypertensive women. FMD is used to measure endothelial function. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection. Laser Doppler flowmetry with cutaneous microdialysis is used to examine vascular function when ET-A and ET-B receptor antagonists is perfused via intradermal microdialysis fibers. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will be assessed. Skin punch biopsy samples will be used to assess for protein expression of ET-A and ET-B receptors. | Drug | Hypertensives |
Primary outcome
ET-1 Mediated Constriction
Time frame: Each participant was assessed at baseline and 2 weeks later.
Cutaneous blood flow is measured via laser Doppler flowmetry during cutaneous microdialysis perfusions of ET-A and ET-B receptor antagonists as previously described by Wenner MM in 2017(see reference list).
1 secondary outcome
Endothelin Receptor A and B Expression
Time frame: Baseline and 2 weeks later
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23283859Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation. 2013 Jan 1;127(1):143-52. doi: 10.1161/CIR.0b013e318282ab8f. No abstract available.
- Background: PubMed 19470884Barton M, Meyer MR. Postmenopausal hypertension: mechanisms and therapy. Hypertension. 2009 Jul;54(1):11-8. doi: 10.1161/HYPERTENSIONAHA.108.120022. Epub 2009 May 26. No abstract available.
- Background: PubMed 16910905Kim JK, Alley D, Seeman T, Karlamangla A, Crimmins E. Recent changes in cardiovascular risk factors among women and men. J Womens Health (Larchmt). 2006 Jul-Aug;15(6):734-46. doi: 10.1089/jwh.2006.15.734.
- Background: PubMed 16914423Yanes LL, Romero DG, Iles JW, Iliescu R, Gomez-Sanchez C, Reckelhoff JF. Sexual dimorphism in the renin-angiotensin system in aging spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2006 Aug;291(2):R383-90. doi: 10.1152/ajpregu.00510.2005. Epub 2006 Mar 30.
- Background: PubMed 20679182Yanes LL, Romero DG, Iliescu R, Zhang H, Davis D, Reckelhoff JF. Postmenopausal hypertension: role of the Renin-Angiotensin system. Hypertension. 2010 Sep;56(3):359-63. doi: 10.1161/HYPERTENSIONAHA.110.152975. Epub 2010 Aug 2.
- Background: PubMed 11358929Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension. 2001 May;37(5):1199-208. doi: 10.1161/01.hyp.37.5.1199.
- Background: PubMed 21509049Yanes LL, Reckelhoff JF. Postmenopausal hypertension. Am J Hypertens. 2011 Jul;24(7):740-9. doi: 10.1038/ajh.2011.71. Epub 2011 Apr 21.
- Background: PubMed 15319224Yanes LL, Romero DG, Cucchiarelli VE, Fortepiani LA, Gomez-Sanchez CE, Santacruz F, Reckelhoff JF. Role of endothelin in mediating postmenopausal hypertension in a rat model. Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R229-33. doi: 10.1152/ajpregu.00697.2003. Epub 2004 Aug 19.
- Background: PubMed 23220478Lima R, Yanes LL, Davis DD, Reckelhoff JF. Roles played by 20-HETE, angiotensin II and endothelin in mediating the hypertension in aging female spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2013 Feb;304(3):R248-51. doi: 10.1152/ajpregu.00380.2012. Epub 2012 Dec 5.
- 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 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.
- Individual participant dataSharing planned: No
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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, Ph.D 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 Phase 4 study testing Normotensive and Hypertensives in people with Cardiovascular Diseases and Hypertension, 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 6 inclusion and 11 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: stopped early, as of the sponsor's last update on 19 Jan 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
ET-1 Mediated Constriction (time frame: Each participant was assessed at baseline and 2 weeks later.). 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 NCT03371823, which also lists 25 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 19 Jan 2022.