Myocardial IschemiaNCT00600106
Data Analyses for Ancillary WISE Femhrt Hormone Replacement Study
A study testing 1/10 NA/EE in people with Myocardial Ischemia, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
The goal of the main trial was to evaluate the effect of low dose hormone replacement therapy with 1 mg norethindrone/10mcg ethinyl estradiol in postmenopausal women with a history of chest discomfort, myocardial ischemia and no obstructive CAD. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Myocardial Ischemia
- What is being tested?
- 1/10 NA/EE
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 1999to Mar 2010
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Postmenopausal WISE and nonWISE study participants
- Normal/minimally diseased coronary arteries (<50% luminal diameter stenosis in all epicardial coronary arteries) within 36 months of ancillary study entry and no intercurrent MI, PTCA, CABG
- Any one (or multiple) of the following criteria suggestive of myocardial ischemia within 36 months of ancillary study entry:
- Abnormal P-31 magnetic resonance spectroscopy (a fall in quantitative PCr/ATP ratio >15% from control) performed at a WISE or nonWISE site
- Positive exercise stress test (> or = 1mm horizontal or downsloping, or > or =1.5mm upsloping ST segment depression measured 0.08 msec after the J point), performed and/or interpretated by a WISE or WISE ancillary ancillary trial investigator
- Reversible stress radionuclide perfusion defect > equivocal and not attributable to breast/imaging artifact. performed as part of the WISE protocol
Show all 10Show fewer
- Coronary artery flow reserve <2.25 performed. as part of using the WISE protocol
- No contraindications to 12 weeks of FemHRT or hormone replacement therapy
- Normal mammogram and pelvic exam (including PAP smear for those with an intact uterus) within 12 months of study entry
- Documented normal liver function testing (SGOT) within 3 months of study entry.
Who cannot join
- Documented myocardial infarction, coronary artery bypass surgery or mechanical revascularization
- Systolic blood pressure >200 mmHg or diastolic blood pressure >105 mmHg
- LDL-cholesterol >190 mg/dl, triglycerides > or = 300 mg/dl
- Clinically significant hepatic or renal dysfunction (SGOT more than 1.2 times normal at baseline, serum creatinine >2)
- Uncontrolled diabetes mellitus (FBS > or = 225 mg/dl) or new onset diabetes until stabilized
- Clinically significant valvular heart disease, dilated cardiomyopathy, or congestive heart failure (NYHA Class IV or severe Class III)
Show all 13Show fewer
- Currently on hormone replacement therapy and unwilling/unable to withdraw treatment prior to study, (participants are eligible for study entry 4-8 weeks following hormone replacement therapy withdrawal, at the discretion of the WISE ancillary trial Principal Investigator)
- Previous breast cancer, mammogram suggestive of cancer, or endometrial cancer without hysterectomy
- Abnormal uterine bleeding or abnormal Pap smear (SIL I, II or III, carcinoma in situ, or cancer)
- Previous deep venous thrombosis, pulmonary embolism, or other thromboembolic disorder.
- Alcoholism or drug abuse
- Participation in any other investigational drug or device study
- Women with elevated diastolic (> or = 90 mm Hg) or systolic (> or = 140 mm Hg) blood pressure, LDL-cholesterol (> or = 160 mg/dl), fasting blood sugar (> or = 130 mg/dl) and women who smoke cigarettes will be told their risk factor levels and referred for evaluation and treatment by their private physician.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Women's Heart Center, 8631 W. 3rd St, Suite 740
Los Angeles, California, 90048
About this study
Official title: WISE Ancillary Study Data Analyses: Efficacy of Hormone Replacement on Myocardial Ischemia in Postmenopausal Women With Normal/Minimal Coronary Artery Disease: Data Analysis
The goal of the main trial was to evaluate the effect of low dose hormone replacement therapy with 1 mg norethindrone/10mcg ethinyl estradiol in postmenopausal women with a history of chest discomfort, myocardial ischemia and no obstructive CAD. For the purposes of this study as a core lab coordinating center, the investigators will be performing P31 MRS core lab analyses; hormone core lab analyses; lipid core lab analyses; glucose, insulin and HOMA core lab analyses; exercise stress test/Holter monitor core lab analyses; brachial artery reactivity test core lab analyses; full study data analyses for manuscript preparation and the writing and submission and publication of manuscript.
The main trial duration: December 1999 - May 2003.
The ancillary data analysis project duration: April 2006 - March 2010.
Read the detailed description
See Brief Summary above.
- Conditions
- Myocardial Ischemia
- Being tested
- 1/10 NA/EE, Placebo
- Medical subject headings
- Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1/10 NA/EEDrug
Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE)
PlaceboDrug
1 mg placebo
| Study group | Role | What they receive |
|---|---|---|
| Hormone replacement therapy | Active comparator | Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE) Receives: Drug: 1/10 NA/EE |
| Placebo | Placebo comparator | 1mg placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inducible Myocardial Ischemia
Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia.
Measured: Baseline
Endothelial Dysfunction (FMD)
Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of endothelial dysfunction.
Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100].
Measured: Baseline
Endothelial Dysfunction (FMD)
Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function.
Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100].
Measured: 12 weeks
Inducible Myocardial Ischemia
Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia.
Measured: 12 weeks
Secondary outcomes (10)
Physical Functional Disability - Functional Capacity (METs)
Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on.
Measured: Baseline
Quality of Life - Menopause Symptoms
Quality of life assessed by menopausal symptoms and psychological questionnaires
Measured: Baseline
Quality of Life - Menopause Symptoms
Quality of life assessed by menopausal symptoms and psychological questionnaires
Measured: 12 weeks
Quality of Life - Health Survey
Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions.
Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: Baseline
Quality of Life - Health Survey
Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions.
Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: 12 weeks
Physical Functional Disability - Functional Capacity (METs)
Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on.
Measured: Exit at 12 weeks
Physical Functional Disability - Functional Capacity (Metabolism Equivalents)
Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.
Measured: Baseline
Physical Functional Disability - Functional Capacity (Metabolism Equivalents)
Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.
Measured: Exit (12 weeks)
Physical Functional Disability - Functional Capacity (Exercise Induced ST Segment Depression)
Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.
In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (>1.0 mm horizontal / downsloping or >1.5 upsloping ST segment depression measured 0.08 msec after the J point).
Measured: Baseline
Physical Functional Disability - Functional Capacity (Stress Induced ST Segment Depression)
Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.
In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (>1.0 mm horizontal / downsloping or >1.5 upsloping ST segment depression measured 0.08 msec after the J point).
Measured: Exit (12 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2008 (estimated)
- Study startDec 1999
- Primary completionMay 2003
- Study completionMar 2010
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 (45)Papers the sponsor has linked to this study.
- Other trials for Myocardial IschemiaStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Parke-Davis, University of Pittsburgh, University of Florida, Allegheny University, University of Alabama at Birmingham, Johns Hopkins University
- Responsible party
- Principal investigator, Noel Bairey Merz, Cedars-Sinai Medical Center
- Investigators
- C. Noel Bairey Merz, MD, Study chair, Cedars-Sinai Medical CenterCarl Pepine, MD, Principal investigator, University of FloridaSteve Reis, MD, Principal investigator, University of PittsburghNathaniel Reichek, MD, Principal investigator, Allegheny University of the Health SciencesWilliam Rogers, MD, Principal investigator, University of Alabama at BirminghamVijay Misra, MD, Principal investigator, University of Alabama at BirminghamRobert B Weiss, MD, Principal investigator, Johns Hopkins UniversitySheryl Kelsey, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00600106
- Sponsor's protocol ID
- 9260
- Other IDs
- IRB#0505140
- Status last verified
- Apr 2019
- First submitted
- 11 Jan 2008
- Last updated
- 24 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Panza JA. Myocardial ischemia and the pains of the heart. N Engl J Med. 2002 Jun 20;346(25):1934-5. doi: 10.1056/NEJMp020047. No abstract available.
PubMed 12075053Cannon RO 3rd. Does coronary endothelial dysfunction cause myocardial ischemia in the absence of obstructive coronary artery disease? Circulation. 1997 Nov 18;96(10):3251-4. No abstract available.
PubMed 9396408Williams JK, Adams MR, Klopfenstein HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation. 1990 May;81(5):1680-7. doi: 10.1161/01.cir.81.5.1680.
PubMed 2331772Williams JK, Shively CA, Clarkson TB. Determinants of coronary artery reactivity in premenopausal female cynomolgus monkeys with diet-induced atherosclerosis. Circulation. 1994 Aug;90(2):983-7. doi: 10.1161/01.cir.90.2.983.
PubMed 8044971Gilligan DM, Quyyumi AA, Cannon RO 3rd. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994 Jun;89(6):2545-51. doi: 10.1161/01.cir.89.6.2545.
PubMed 8205663Reis SE, Gloth ST, Blumenthal RS, Resar JR, Zacur HA, Gerstenblith G, Brinker JA. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation. 1994 Jan;89(1):52-60. doi: 10.1161/01.cir.89.1.52.
PubMed 8281693Merz CN, Kelsey SF, Pepine CJ, Reichek N, Reis SE, Rogers WJ, Sharaf BL, Sopko G. The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report. J Am Coll Cardiol. 1999 May;33(6):1453-61. doi: 10.1016/s0735-1097(99)00082-0.
PubMed 10334408Sharaf BL, Pepine CJ, Kerensky RA, Reis SE, Reichek N, Rogers WJ, Sopko G, Kelsey SF, Holubkov R, Olson M, Miele NJ, Williams DO, Merz CN; WISE Study Group. Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory). Am J Cardiol. 2001 Apr 15;87(8):937-41; A3. doi: 10.1016/s0002-9149(01)01424-2.
PubMed 11305981The manual of laboratory operations 1. Lipid and lipoprotein analysis. Bethesda: Lipid Research Clinics Program. National Institutes of Health. DHEW Publication No. 75-628; 1974.
Barrett-Connor E, Goodman-Gruen D. Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women. BMJ. 1995 Nov 4;311(7014):1193-6. doi: 10.1136/bmj.311.7014.1193.
PubMed 7488894Helmer DC, Ragland DR, Syme SL. Hostility and coronary artery disease. Am J Epidemiol. 1991 Jan 15;133(2):112-22. doi: 10.1093/oxfordjournals.aje.a115850.
PubMed 1985442Naughton MJ, Shumaker SA, Anderson RT, et al. Psychological aspects of health-related quality of life measurement: tests and scales. Philadelphia: Lippincott-Raven Publishers; 1996.
MANDLER G, MANDLER JM, UVILLER ET. Autonomic feedback: the perception of autonomic activity. J Abnorm Psychol. 1958 May;56(3):367-73. doi: 10.1037/h0048083. No abstract available.
PubMed 13538604Ware JE, Kosinski M, Gandek B. SF-36 Health Survey. Manual and interpretation guide. Lincoln: Quality Metric Inc.; 1993.
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.
PubMed 1593914
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- WISE Ancillary Study Data Analyses: Efficacy of Hormone Replacement on Myocardial Ischemia in Postmenopausal Women With Normal/Minimal Coronary Artery Disease: Data Analysis
- ClinicalTrials.gov ID
- NCT00600106
- Acronym / sponsor ID
- 9260
- Conditions
- Myocardial Ischemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- Parke-Davis, University of Pittsburgh, University of Florida, Allegheny University, University of Alabama at Birmingham, Johns Hopkins University
- Study start
- Dec 1999
- Primary completion
- May 2003 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 24 Jan 2008 (estimated)
- Results
- Posted 19 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the main trial was to evaluate the effect of low dose hormone replacement therapy with 1 mg norethindrone/10mcg ethinyl estradiol in postmenopausal women with a history of chest discomfort, myocardial ischemia and no obstructive CAD. For the purposes of this study as a core lab coordinating center, the investigators will be performing P31 MRS core lab analyses; hormone core lab analyses; lipid core lab analyses; glucose, insulin and HOMA core lab analyses; exercise stress test/Holter monitor core lab analyses; brachial artery reactivity test core lab analyses; full study data analyses for manuscript preparation and the writing and submission and publication of manuscript.
The main trial duration: December 1999 - May 2003.
The ancillary data analysis project duration: April 2006 - March 2010.
Detailed description
See Brief Summary above.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hormone replacement therapy | Active comparator | Drug: 1/10 NA/EEHormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE) |
| Placebo | Placebo comparator | Drug: Placebo1mg placebo |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Postmenopausal WISE and nonWISE study participants
- Normal/minimally diseased coronary arteries (<50% luminal diameter stenosis in all epicardial coronary arteries) within 36 months of ancillary study entry and no intercurrent MI, PTCA, CABG
- Any one (or multiple) of the following criteria suggestive of myocardial ischemia within 36 months of ancillary study entry:
- No contraindications to 12 weeks of FemHRT or hormone replacement therapy
- Normal mammogram and pelvic exam (including PAP smear for those with an intact uterus) within 12 months of study entry
Key exclusion criteria (13 listed)
- Documented myocardial infarction, coronary artery bypass surgery or mechanical revascularization
- Systolic blood pressure >200 mmHg or diastolic blood pressure >105 mmHg
- LDL-cholesterol >190 mg/dl, triglycerides > or = 300 mg/dl
- Clinically significant hepatic or renal dysfunction (SGOT more than 1.2 times normal at baseline, serum creatinine >2)
- Uncontrolled diabetes mellitus (FBS > or = 225 mg/dl) or new onset diabetes until stabilized
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 |
|---|---|---|
| 1/10 NA/EEHormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE) | Drug | Hormone replacement therapy |
| Placebo1 mg placebo | Drug | Placebo |
Primary outcome
Inducible Myocardial Ischemia
Time frame: Baseline
Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia.
Endothelial Dysfunction (FMD)
Time frame: Baseline
Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of endothelial dysfunction. Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100].
Endothelial Dysfunction (FMD)
Time frame: 12 weeks
Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100].
Inducible Myocardial Ischemia
Time frame: 12 weeks
Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia.
10 secondary outcomes
Physical Functional Disability - Functional Capacity (METs)
Time frame: Baseline
Quality of Life - Menopause Symptoms
Time frame: Baseline
Quality of Life - Menopause Symptoms
Time frame: 12 weeks
Quality of Life - Health Survey
Time frame: Baseline
Quality of Life - Health Survey
Time frame: 12 weeks
Physical Functional Disability - Functional Capacity (METs)
Time frame: Exit at 12 weeks
Physical Functional Disability - Functional Capacity (Metabolism Equivalents)
Time frame: Baseline
Physical Functional Disability - Functional Capacity (Metabolism Equivalents)
Time frame: Exit (12 weeks)
Physical Functional Disability - Functional Capacity (Exercise Induced ST Segment Depression)
Time frame: Baseline
Physical Functional Disability - Functional Capacity (Stress Induced ST Segment Depression)
Time frame: Exit (12 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12075053Panza JA. Myocardial ischemia and the pains of the heart. N Engl J Med. 2002 Jun 20;346(25):1934-5. doi: 10.1056/NEJMp020047. No abstract available.
- Background: PubMed 9396408Cannon RO 3rd. Does coronary endothelial dysfunction cause myocardial ischemia in the absence of obstructive coronary artery disease? Circulation. 1997 Nov 18;96(10):3251-4. No abstract available.
- Background: PubMed 2331772Williams JK, Adams MR, Klopfenstein HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation. 1990 May;81(5):1680-7. doi: 10.1161/01.cir.81.5.1680.
- Background: PubMed 8044971Williams JK, Shively CA, Clarkson TB. Determinants of coronary artery reactivity in premenopausal female cynomolgus monkeys with diet-induced atherosclerosis. Circulation. 1994 Aug;90(2):983-7. doi: 10.1161/01.cir.90.2.983.
- Background: PubMed 8205663Gilligan DM, Quyyumi AA, Cannon RO 3rd. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994 Jun;89(6):2545-51. doi: 10.1161/01.cir.89.6.2545.
- Background: PubMed 8281693Reis SE, Gloth ST, Blumenthal RS, Resar JR, Zacur HA, Gerstenblith G, Brinker JA. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation. 1994 Jan;89(1):52-60. doi: 10.1161/01.cir.89.1.52.
- Background: PubMed 10334408Merz CN, Kelsey SF, Pepine CJ, Reichek N, Reis SE, Rogers WJ, Sharaf BL, Sopko G. The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report. J Am Coll Cardiol. 1999 May;33(6):1453-61. doi: 10.1016/s0735-1097(99)00082-0.
- Background: PubMed 11305981Sharaf BL, Pepine CJ, Kerensky RA, Reis SE, Reichek N, Rogers WJ, Sopko G, Kelsey SF, Holubkov R, Olson M, Miele NJ, Williams DO, Merz CN; WISE Study Group. Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory). Am J Cardiol. 2001 Apr 15;87(8):937-41; A3. doi: 10.1016/s0002-9149(01)01424-2.
- BackgroundThe manual of laboratory operations 1. Lipid and lipoprotein analysis. Bethesda: Lipid Research Clinics Program. National Institutes of Health. DHEW Publication No. 75-628; 1974.
- Background: PubMed 7488894Barrett-Connor E, Goodman-Gruen D. Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women. BMJ. 1995 Nov 4;311(7014):1193-6. doi: 10.1136/bmj.311.7014.1193.
- Background: PubMed 1985442Helmer DC, Ragland DR, Syme SL. Hostility and coronary artery disease. Am J Epidemiol. 1991 Jan 15;133(2):112-22. doi: 10.1093/oxfordjournals.aje.a115850.
- BackgroundNaughton MJ, Shumaker SA, Anderson RT, et al. Psychological aspects of health-related quality of life measurement: tests and scales. Philadelphia: Lippincott-Raven Publishers; 1996.
- 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.
C. Noel Bairey Merz, MD study chair
Cedars-Sinai Medical Center
Carl Pepine, MD principal investigator
University of Florida
Steve Reis, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 1/10 NA/EE in people with Myocardial Ischemia, run by Cedars-Sinai Medical Center 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 10 inclusion and 13 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 Apr 2019. 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 19 Dec 2017). 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?
Inducible Myocardial Ischemia (time frame: Baseline). The study lists 4 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 NCT00600106, which also lists 45 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 Apr 2019.