Arterial StiffeningSHAPENCT00608062
Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women
A study testing GnRHant - Ganirelix acetate and Transdermal estradiol patch in people with Arterial Stiffening and Aging, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to find out why women's arteries stiffen as they go through menopause, and how this is affected by estrogen loss. We believe that arteries stiffen with the loss of estrogen because of "oxidative stress," the production of molecules that can damage cells and tissues in the body, and because… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Arterial Stiffening, Aging, Menopause
- What is being tested?
- GnRHant - Ganirelix acetate and Transdermal estradiol patch
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 155 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to 25 Oct 2012
- Phase
- Interventional
- 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 18 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy women of all races and ethnic backgrounds in one of the following groups:
- Premenopausal: 18-49 years, regular menstrual cycles with no change in observed cycle length (21-35 days)
- Perimenopausal: 40-55 years, categorized as either early (at least 2 cycles with cycle length changes of at least 7 days) or late (more than 3 months of amenorrhea) transition
- Postmenopausal: 45-70 years, more than 12 months of amenorrhea as defined by the menopausal staging system (STRAW); additionally, postmenopausal women will be categorized into early and late stages as defined by the STRAW definition, specifically, women who are less than 5 years postmenopause will be considered early, and women more than 6 years will be categorized as late
- All postmenopausal women will have undergone natural menopause
- No oral contraceptive or Hormone Replacement Therapy (HRT) use for at least 6 months
Show all 12Show fewer
- Resting blood pressure less than 140/90 mmHg
- Plasma glucose concentrations less than 110 mg/dl under fasting conditions
- Sedentary or recreationally active (less than 3 days of vigorous aerobic exercise)
- No use of medications that might influence cardiovascular function
- Nonsmokers
- No use of vitamin supplements or willing to stop use for duration of the study
Who cannot join
- History of or active estrogen-dependent neoplasms, acute liver or gallbladder disease, vaginal bleeding, venous thromboembolism, hypertriglyceridemia, and cardiovascular disease
- Known allergy to transdermal patch or GnRHant
- Other contraindications to HRT and GnRHant
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research Laboratory
Aurora, Colorado, 80045
About this study
Official title: Biological Mechanisms of Arterial Stiffening With Age and Estrogen Deficiency
The purpose of this study is to find out why women's arteries stiffen as they go through menopause, and how this is affected by estrogen loss. We believe that arteries stiffen with the loss of estrogen because of "oxidative stress," the production of molecules that can damage cells and tissues in the body, and because the arteries lose their ability to expand, or dilate.
Read the detailed description
As women get older and go through menopause, estradiol levels decrease. Also with aging, the arteries that are located around the heart get stiffer. Over time this increase in arterial stiffness can lead to a number of health problems such as high blood pressure and heart disease. In this study we want to find out if a short-term drop in estrogen levels in premenopausal and perimenopausal women can cause arteries to become stiffer, and why this happens. Additionally, in postmenopausal women, we want to find out if a short-term increase in estrogen levels causes their arteries to become more flexible (less stiff).
Arterial health (i.e., stiffness) will be examined in premenopausal, perimenopausal and postmenopausal women before and after they are given a drug called Ganirelix™ (for 7 days), which will markedly lower their reproductive hormones. After the first 4 days of taking Ganirelix™, the women will be randomly placed into 1 of 2 treatment groups to take either estrogen (0.075 mg/d skin patch) replacement or placebo for the rest of the Ganirelix treatment. This is to increase estrogen levels back to the normal level. After having the patch on for 4 days, arterial health will be examined again.
Pre-specified Outcome Measures were divided into unit-of-measurement specific Outcome Measure tables for the purposes of results reporting to ClinicalTrials.gov
- Conditions
- Arterial Stiffening, Aging, Menopause
- Being tested
- GnRHant - Ganirelix acetate, Transdermal estradiol patch, Transdermal placebo patch
- Keywords
- endothelial function, women, female, estrogen deficiency, sex hormones, adiposity, oxidative stress, antioxidants
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRHant - Ganirelix acetateDrug
Also called Ganirelix
1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7
Transdermal estradiol patchDrug
0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Transdermal placebo patchDrug
Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
| Study group | Role | What they receive |
|---|---|---|
| Pre1 | Experimental | Premenopausal - GnRHant plus estradiol Receives: Drug: GnRHant - Ganirelix acetate; Drug: Transdermal estradiol patch |
| Pre2 | Placebo comparator | Premenopausal - GnRHant plus placebo Receives: Drug: GnRHant - Ganirelix acetate; Drug: Transdermal placebo patch |
| Peri1 | Experimental | Perimenopausal (early) - GnRHant plus estradiol Receives: Drug: GnRHant - Ganirelix acetate; Drug: Transdermal estradiol patch |
| Peri2 | Placebo comparator | Perimenopausal (early) - GnRHant plus placebo Receives: Drug: GnRHant - Ganirelix acetate; Drug: Transdermal placebo patch |
| Peri3 | Experimental | Perimenopausal (late) - GnRHant plus estradiol Receives: Drug: GnRHant - Ganirelix acetate; Drug: Transdermal estradiol patch |
| Peri4 | Placebo comparator | Perimenopausal (late) - GnRHant plus placebo Receives: Drug: GnRHant - Ganirelix acetate; Drug: Transdermal placebo patch |
| Post1 | Experimental | Postmenopausal - GnRHant plus estradiol Receives: Drug: GnRHant - Ganirelix acetate; Drug: Transdermal estradiol patch |
| Post2 | Placebo comparator | Postmenopausal - GnRHant plus placebo Receives: Drug: GnRHant - Ganirelix acetate; Drug: Transdermal placebo patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arterial Stiffness (Carotid Artery Compliance) During Saline
Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure
Measured: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment
Endothelial Function
Brachial artery flow-mediated dilation (FMD) assessed by ultrasound. This other outcome measure was originally specified as "Secondary" in error and has been updated to "Primary" to be consistent with the protocol.
Measured: Baseline, day 4 of GnRHant and Day 7 of GnRHant and estradiol or placebo treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2008 (estimated)
- Study startMar 2007
- Primary completion25 Oct 2012
- Study completion25 Oct 2012
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 (8)Papers the sponsor has linked to this study.
- Other trials for Arterial StiffeningStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Kerrie L Moreau, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00608062
- Sponsor's protocol ID
- 06-0537
- Other IDs
- R01AG027678
- Acronym
- SHAPE
- Status last verified
- Dec 2020
- First submitted
- 31 Jan 2008
- Last updated
- 24 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res. 2003 Mar;57(3):861-8. doi: 10.1016/s0008-6363(02)00777-0.
PubMed 12618248Moreau KL, Gavin KM, Plum AE, Seals DR. Ascorbic acid selectively improves large elastic artery compliance in postmenopausal women. Hypertension. 2005 Jun;45(6):1107-12. doi: 10.1161/01.HYP.0000165678.63373.8c. Epub 2005 May 2.
PubMed 15867135Virdis A, Ghiadoni L, Pinto S, Lombardo M, Petraglia F, Gennazzani A, Buralli S, Taddei S, Salvetti A. Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women. Circulation. 2000 May 16;101(19):2258-63. doi: 10.1161/01.cir.101.19.2258.
PubMed 10811592Ihionkhan CE, Chambliss KL, Gibson LL, Hahner LD, Mendelsohn ME, Shaul PW. Estrogen causes dynamic alterations in endothelial estrogen receptor expression. Circ Res. 2002 Nov 1;91(9):814-20. doi: 10.1161/01.res.0000038304.62046.4c.
PubMed 12411396Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol. 2004 Apr 1;556(Pt 1):315-24. doi: 10.1113/jphysiol.2003.057042. Epub 2004 Jan 30.
PubMed 14754992Gavin KM, Jankowski C, Kohrt WM, Stauffer BL, Seals DR, Moreau KL. Hysterectomy is associated with large artery stiffening in estrogen-deficient postmenopausal women. Menopause. 2012 Sep;19(9):1000-7. doi: 10.1097/gme.0b013e31825040f9.
PubMed 22692329Moreau KL, Meditz A, Deane KD, Kohrt WM. Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1211-8. doi: 10.1152/ajpheart.01065.2011. Epub 2012 Jan 13.
PubMed 22245769Moreau KL, Hildreth KL, Meditz AL, Deane KD, Kohrt WM. Endothelial function is impaired across the stages of the menopause transition in healthy women. J Clin Endocrinol Metab. 2012 Dec;97(12):4692-700. doi: 10.1210/jc.2012-2244. Epub 2012 Sep 11.
PubMed 22969140
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biological Mechanisms of Arterial Stiffening With Age and Estrogen Deficiency
- ClinicalTrials.gov ID
- NCT00608062
- Acronym / sponsor ID
- SHAPE / 06-0537
- Conditions
- Arterial Stiffening, Aging, Menopause
- Keywords
- endothelial function, women, female, estrogen deficiency, sex hormones, adiposity, oxidative stress, antioxidants
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 155 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Mar 2007
- Primary completion
- 25 Oct 2012 (actual)
- Study completion
- 25 Oct 2012 (actual)
- First posted
- 6 Feb 2008 (estimated)
- Results
- Posted 24 Dec 2020
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 find out why women's arteries stiffen as they go through menopause, and how this is affected by estrogen loss. We believe that arteries stiffen with the loss of estrogen because of "oxidative stress," the production of molecules that can damage cells and tissues in the body, and because the arteries lose their ability to expand, or dilate.
Detailed description
As women get older and go through menopause, estradiol levels decrease. Also with aging, the arteries that are located around the heart get stiffer. Over time this increase in arterial stiffness can lead to a number of health problems such as high blood pressure and heart disease. In this study we want to find out if a short-term drop in estrogen levels in premenopausal and perimenopausal women can cause arteries to become stiffer, and why this happens. Additionally, in postmenopausal women, we want to find out if a short-term increase in estrogen levels causes their arteries to become more flexible (less stiff).
Arterial health (i.e., stiffness) will be examined in premenopausal, perimenopausal and postmenopausal women before and after they are given a drug called Ganirelix™ (for 7 days), which will markedly lower their reproductive hormones. After the first 4 days of taking Ganirelix™, the women will be randomly placed into 1 of 2 treatment groups to take either estrogen (0.075 mg/d skin patch) replacement or placebo for the rest of the Ganirelix treatment. This is to increase estrogen levels back to the normal level. After having the patch on for 4 days, arterial health will be examined again.
Pre-specified Outcome Measures were divided into unit-of-measurement specific Outcome Measure tables for the purposes of results reporting to ClinicalTrials.gov
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Pre1 | Experimental | Drug: GnRHant - Ganirelix acetate, Drug: Transdermal estradiol patchPremenopausal - GnRHant plus estradiol |
| Pre2 | Placebo comparator | Drug: GnRHant - Ganirelix acetate, Drug: Transdermal placebo patchPremenopausal - GnRHant plus placebo |
| Peri1 | Experimental | Drug: GnRHant - Ganirelix acetate, Drug: Transdermal estradiol patchPerimenopausal (early) - GnRHant plus estradiol |
| Peri2 | Placebo comparator | Drug: GnRHant - Ganirelix acetate, Drug: Transdermal placebo patchPerimenopausal (early) - GnRHant plus placebo |
| Peri3 | Experimental | Drug: GnRHant - Ganirelix acetate, Drug: Transdermal estradiol patchPerimenopausal (late) - GnRHant plus estradiol |
| Peri4 | Placebo comparator | Drug: GnRHant - Ganirelix acetate, Drug: Transdermal placebo patchPerimenopausal (late) - GnRHant plus placebo |
| Post1 | Experimental | Drug: GnRHant - Ganirelix acetate, Drug: Transdermal estradiol patchPostmenopausal - GnRHant plus estradiol |
| Post2 | Placebo comparator | Drug: GnRHant - Ganirelix acetate, Drug: Transdermal placebo patchPostmenopausal - GnRHant plus placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Healthy women of all races and ethnic backgrounds in one of the following groups:
- All postmenopausal women will have undergone natural menopause
- No oral contraceptive or Hormone Replacement Therapy (HRT) use for at least 6 months
- Resting blood pressure less than 140/90 mmHg
- Plasma glucose concentrations less than 110 mg/dl under fasting conditions
Key exclusion criteria (3 listed)
- History of or active estrogen-dependent neoplasms, acute liver or gallbladder disease, vaginal bleeding, venous thromboembolism, hypertriglyceridemia, and cardiovascular disease
- Known allergy to transdermal patch or GnRHant
- Other contraindications to HRT and GnRHant
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 |
|---|---|---|
| GnRHant - Ganirelix acetateAlso: Ganirelix1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 | Drug | Peri1, Peri2, Peri3, Peri4, Post1, Post2, Pre1, Pre2 |
| Transdermal estradiol patch0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7) | Drug | Peri1, Peri3, Post1, Pre1 |
| Transdermal placebo patchStarting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7) | Drug | Peri2, Peri4, Post2, Pre2 |
Primary outcome
Arterial Stiffness (Carotid Artery Compliance) During Saline
Time frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment
Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure
Endothelial Function
Time frame: Baseline, day 4 of GnRHant and Day 7 of GnRHant and estradiol or placebo treatment
Brachial artery flow-mediated dilation (FMD) assessed by ultrasound. This other outcome measure was originally specified as "Secondary" in error and has been updated to "Primary" to be consistent with the protocol.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12618248Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res. 2003 Mar;57(3):861-8. doi: 10.1016/s0008-6363(02)00777-0.
- Background: PubMed 15867135Moreau KL, Gavin KM, Plum AE, Seals DR. Ascorbic acid selectively improves large elastic artery compliance in postmenopausal women. Hypertension. 2005 Jun;45(6):1107-12. doi: 10.1161/01.HYP.0000165678.63373.8c. Epub 2005 May 2.
- Background: PubMed 10811592Virdis A, Ghiadoni L, Pinto S, Lombardo M, Petraglia F, Gennazzani A, Buralli S, Taddei S, Salvetti A. Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women. Circulation. 2000 May 16;101(19):2258-63. doi: 10.1161/01.cir.101.19.2258.
- Background: PubMed 12411396Ihionkhan CE, Chambliss KL, Gibson LL, Hahner LD, Mendelsohn ME, Shaul PW. Estrogen causes dynamic alterations in endothelial estrogen receptor expression. Circ Res. 2002 Nov 1;91(9):814-20. doi: 10.1161/01.res.0000038304.62046.4c.
- Background: PubMed 14754992Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol. 2004 Apr 1;556(Pt 1):315-24. doi: 10.1113/jphysiol.2003.057042. Epub 2004 Jan 30.
- Background: PubMed 22692329Gavin KM, Jankowski C, Kohrt WM, Stauffer BL, Seals DR, Moreau KL. Hysterectomy is associated with large artery stiffening in estrogen-deficient postmenopausal women. Menopause. 2012 Sep;19(9):1000-7. doi: 10.1097/gme.0b013e31825040f9.
- Background: PubMed 22245769Moreau KL, Meditz A, Deane KD, Kohrt WM. Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1211-8. doi: 10.1152/ajpheart.01065.2011. Epub 2012 Jan 13.
- Results publication: PubMed 22969140Moreau KL, Hildreth KL, Meditz AL, Deane KD, Kohrt WM. Endothelial function is impaired across the stages of the menopause transition in healthy women. J Clin Endocrinol Metab. 2012 Dec;97(12):4692-700. doi: 10.1210/jc.2012-2244. Epub 2012 Sep 11.
- 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.
Kerrie L Moreau, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GnRHant - Ganirelix acetate and Transdermal estradiol patch in people with Arterial Stiffening and Aging, run by University of Colorado, Denver 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 12 inclusion and 3 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 24 Dec 2020. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 24 Dec 2020). 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?
Arterial Stiffness (Carotid Artery Compliance) During Saline (time frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment). The study lists 2 primary outcomes in all. 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 NCT00608062, which also lists 8 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 24 Dec 2020.