Stress Response Study for Heart Issues

Recruiting at 3 trial locations

Overseen By Puja K Mehta, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Emory University

Must not be taking: Cardiac medications

Disqualifiers: Hypertension, Diabetes, Hyperlipidemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how stress impacts women with heart problems, specifically focusing on Coronary Microvascular Dysfunction (CMD). Researchers aim to determine if stress affects small heart vessels and overall heart function differently in women with CMD compared to those with other heart conditions or no heart issues. Participants will undergo various tests, including stress tests and heart imaging, to gather data about their heart and stress response. Women who experience chest pain and have been diagnosed with CMD without major artery blockages might be suitable for this study. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research that could enhance understanding and treatment of CMD in women.

Will I have to stop taking my current medications?

The trial requires that participants be able to safely withdraw medications for mental stress testing. If you cannot safely stop your medications, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments for coronary artery disease (CAD), such as certain medications, are usually well-tolerated. These include drugs like ACE inhibitors and beta blockers, which help manage blood pressure and reduce heart strain. Most people taking these medications experience few side effects.

This study focuses on coronary microvascular dysfunction (CMD) in women and will not introduce new or experimental drugs. Instead, participants will undergo tests to assess how stress affects their heart and blood vessels. These tests are safe and non-invasive, meaning they don't involve surgery or entering the body. Participants might undergo physical exams, stress tests, and heart imaging. They will also use devices at home to track factors like heart rate and mood.

Overall, the procedures in this study are routine and have a strong safety record. Since no new medication is introduced, the study emphasizes observation and data collection, minimizing risk. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to uncover new insights into how stress responses affect heart health, particularly in women with coronary microvascular dysfunction (CMD) and those with chronic obstructive coronary artery disease (oCAD). Current treatments often focus on managing symptoms of obstructive coronary artery disease using medications like nitrates, beta-blockers, or calcium channel blockers. However, this study explores the underlying physiological differences between symptomatic women with CMD, those with oCAD, and asymptomatic women, which could lead to more personalized and effective treatments. The trial could reveal crucial differences in myocardial flow reserve and stress response, potentially leading to novel interventions for heart conditions where traditional treatments might not be as effective. Ultimately, the findings could pave the way for tailored therapies that better address the specific needs of each group.

What evidence suggests that this trial's treatments could be effective for coronary microvascular dysfunction?

Research has shown that certain treatments may help women with Coronary Microvascular Dysfunction (CMD). For example, ACE inhibitors (ACEIs) might improve the condition of patients with microvascular angina, a type of chest pain. Additionally, combining strong cholesterol-lowering drugs (statins) with ACEIs or similar medications could effectively manage CMD. These treatments aim to improve blood flow in the small heart vessels, potentially reducing symptoms like chest pain. This trial will compare symptomatic women with CMD to those with chronic obstructive CAD and asymptomatic control women. While the study focuses on understanding stress responses, these treatment options offer hope for effectively managing CMD symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Puja K Mehta

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for women over 50 with menopause-related chest pain and Coronary Microvascular Dysfunction (CMD), who can consent to tests. They must be willing to undergo a cardiac scan, mental stress testing, and have no acute illnesses or diabetes. Excluded are those with severe heart issues, uncontrolled hypertension, recent heart attacks, certain blood conditions, or significant artery blockages.

Inclusion Criteria

Willing to sign the informed consent

I have never been diagnosed with heart disease.

I am healthy with no heart disease risk factors.

Exclusion Criteria

My blood pressure is not higher than 180/100.

I have a serious blood disorder or significant anemia.

LDL >120 mg/dL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including physical exams, blood tests, and stress tests

1 week

1 visit (in-person)

Mental Stress Testing

Participants undergo mental stress tests including speech and math tasks, with monitoring of autonomic and vascular responses

1 week

Multiple visits (in-person)

Home Monitoring

Participants use home devices to monitor autonomic function, sleep, mood, and stress levels

1 week

Follow-up

Participants are monitored for changes in quality of life and anginal symptoms

12 months

Periodic follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Study Procedures

Trial Overview

The study investigates how mental stress affects the autonomic function in postmenopausal women with CMD compared to others. It involves physical exams, blood tests, imaging of the heart and vessels, plus home monitoring of autonomic function and daily stress levels for one week.

How Is the Trial Designed?

Group I: Symptomatic women with no obstructive CAD who have CMD Experimental Treatment 1 Intervention

Symptomatic women with chest pain and no obstructive CAD who have an abnormal myocardial flow reserve (MFR \< 2.5)

Group II: Symptomatic women with chronic obstructive CAD (oCAD) Experimental Treatment 1 Intervention

This group will serve as one comparison group since these women represent the prevailing paradigm of ischemia from obstructive stenosis while sharing common cardiovascular risk factors with the CMD group.

Group III: Asymptomatic control women with no prior history of CAD or angina Active Control 1 Intervention

Asymptomatic control women with no prior history of CAD or angina, who are age-matched to the CMD women; not on any cardiac medications, who will also have to pass a maximal Bruce protocol exercise treadmill test.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 107 elderly patients with stable angina, both trimetazidine and ranolazine combined with bisoprolol and ivabradine significantly improved exercise tolerance and quality of life after 6 months of treatment.

Trimetazidine was found to be more effective than ranolazine in reducing silent ST-segment depression, making it the preferred choice for treating silent myocardial ischemia in this patient population due to its higher efficacy and lower cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Triple antianginal combinations in the treatment of elderly and senile patients with stable angina]. Kanorskii, SG., Smolenskaya, NV.[2018]

A study involving 298 participants (ages 20 to 60) found that stress significantly affects cardiovascular responses, particularly through changes in stroke volume and total peripheral resistance, which are important for understanding stress-induced blood pressure increases.

In hypertensive patients treated with various antihypertensive medications, only beta-blockers (oxprenolol) and calcium antagonists (nitrendipine) showed significant changes in heart rate and peripheral resistance during stress, while other treatments did not alter the hemodynamic response to emotional stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic response patterns to mental stress: diagnostic and therapeutic implications. Rüddel, H., Langewitz, W., Schächinger, H., et al.[2019]

In a study involving 36 participants (6 healthy volunteers and 30 hypertensive patients), both amlodipine and lacidipine did not change the body's blood pressure and heart rate responses to stress from cold exposure or isometric exercise.

While these calcium antagonists effectively lowered resting blood pressure in hypertensive patients, they did not influence the increased blood pressure and heart rate caused by stress, indicating that their efficacy may not extend to stress-induced cardiovascular reactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of calcium antagonists on stress-induced rise in blood pressure and heart rate: a double-blind, placebo-controlled study. Malhotra, S., Kumari, S., Pandhi, P.[2019]

Ranolazine is an effective treatment for chronic stable angina pectoris, as demonstrated in three randomized trials that showed it can increase exercise capacity and reduce anginal episodes.

While ranolazine is generally safe and can be used alongside traditional angina medications, it may cause side effects like dizziness and constipation, and it has the potential to prolong the QT(c) interval, which requires monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranolazine for chronic stable angina. Nash, DT., Nash, SD.[2015]

A systematic review of three major trials involving 29,805 patients showed that ACE inhibitors significantly reduce all-cause mortality and cardiovascular events in patients with atherosclerosis, even if they do not have heart failure or left ventricular systolic dysfunction.

ACE inhibitors were associated with lower rates of cardiovascular mortality, non-fatal myocardial infarction, and strokes, suggesting they are beneficial for a broader range of patients with atherosclerosis, not just those with existing heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Dagenais, GR., Pogue, J., Fox, K., et al.[2020]

In a study of 30 healthy normotensive subjects, the beta-blocker bisoprolol significantly reduced cardiovascular reactivity to mental stress, with 6 out of 15 treated individuals becoming non-reactive compared to those on placebo.

The findings suggest that bisoprolol may help prevent future hypertension by mitigating hyperreactive blood pressure responses during stress, indicating its potential as a preventive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiovascular response to mental and physical stress in hyper-reactive normotensive subjects. Beta blockade effect]. Przybylski, J., Resnik, M., Corsi, M., et al.[2013]

In a 6-week study involving 52 men with mild-to-moderate hypertension, isradipine effectively reduced diastolic blood pressure responses to mental stress without significantly altering cardiac output or total peripheral resistance.

Metoprolol decreased cardiac output but increased total peripheral resistance, leading to a greater blood pressure response to stress, indicating that while it reduces heart responsiveness, it may not effectively lower blood pressure under stress due to compensatory vascular mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological modulation of stress-induced cardiovascular hyperreactivity in essential hypertension. Schulte, W., Rüddel, H., Schmieder, R., et al.[2013]

Ranolazine is a newly approved antianginal medication that can be used as an add-on therapy for patients with stable angina who still experience symptoms despite optimal treatment with traditional medications like beta-blockers and nitrates.

This review emphasizes ranolazine's unique mechanism of action and its favorable tolerability profile, suggesting it may provide clinical benefits without the common side effects associated with other antianginal therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ranolazine in the treatment of chronic stable angina]. Gustapane, M., Cardillo, MT., Biasillo, G., et al.[2015]

The HOPE study demonstrated that the ACE inhibitor ramipril significantly reduces the risk of major cardiovascular events, such as heart attacks and strokes, in high-risk patients, with a relative risk reduction of 22% compared to placebo.

In diabetic patients, ramipril showed even greater efficacy, reducing the combined risk of cardiovascular death, non-fatal heart attacks, and strokes by 25%, suggesting benefits beyond just lowering blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The HOPE Study (Heart Outcomes Prevention Evaluation). Sleight, P.[2013]

Ranolazine is an innovative treatment for stable angina pectoris that uniquely does not affect heart rate or systemic blood pressure, making it a safer option for patients.

The drug works by inhibiting the late sodium current, which helps prevent calcium overload in heart cells, and it shows potential for treating other conditions like atrial fibrillation and diastolic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ranolazine--an additional anti-anginal drug]. Michels, G., Kochanek, M., Hoppe, UC.[2015]

The hand grip test (HGT) elicited the highest cardiovascular reactivity (CVR) in a study of 82 young Indian adults, making it the most effective stressor for generating maximum CVR.

In contrast, the cold pressor task (CPT) revealed significant gender differences in CVR, while the video game stressor did not produce meaningful changes in heart rate or blood pressure, indicating it is not perceived as a stressor by this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular reactivity to stressors in Indian young adults with normotensive parents. Verma, A., Kumar, M., Saxena, I., et al.[2021]

Ranolazine is a new medication approved for treating angina that works by preventing sodium-induced calcium overload in heart cells, which helps reduce ischemia without causing low blood pressure or slow heart rate, common side effects of other treatments.

This review evaluates ranolazine's pharmacology and clinical trial data, highlighting its safety and efficacy in treating chronic stable angina and acute coronary syndrome, marking it as the first new angina treatment approved in the USA in over a decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranolazine: a novel agent that improves dysfunctional sodium channels. Pham, DQ., Mehta, M.[2015]

ACE inhibitors, like ramipril, are effective not only in lowering blood pressure and treating heart failure but also in preventing ischemic events such as myocardial infarction (MI) in patients at risk, as shown in the large HOPE trial with a diverse group of participants.

The HOPE trial demonstrated that ramipril significantly reduces the risk of MI and other cardiovascular events in patients without heart failure or left ventricular dysfunction, suggesting its broader application in cardiovascular disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anti-ischemic potential of angiotensin-converting enzyme inhibition: insights from the heart outcomes prevention evaluation trial. Pitt, B.[2020]

Heart failure affects about 5 million adults in the U.S., and current treatments focus on regulating overactive systems in the body, specifically the renin-angiotensin-aldosterone and sympathetic autonomic systems.

The 2016 guidelines introduced two new medications, valsartan/sacubitril and ivabradine, which have shown additional benefits in reducing mortality and morbidity in heart failure patients with reduced ejection fraction, beyond the improvements already seen with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart failure guidelines: What's new? Papadimitriou, L., Hamo, CE., Butler, J.[2021]

Angiotensin II receptor blockers (ARBs) may offer additional benefits over ACE inhibitors in treating heart failure by more effectively blocking the harmful effects of angiotensin II, making them suitable for patients who cannot tolerate ACE inhibitors.

Clinical trials have shown that ARBs improve morbidity and mortality outcomes in heart failure patients, and when combined with spironolactone, they provide even greater benefits, leading to their recommendation in recent treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on therapy for heart failure. DiBianco, R.[2019]

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