Medical Therapy for Myocardial Bridging

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests beta blockers and calcium channel blockers on adults with chest pain and myocardial bridges but no blocked arteries. These medications may help by relaxing heart muscles and improving blood flow, potentially reducing chest pain. Beta blockers and calcium channel blockers have been shown to be effective in treating angina pectoris, often used in combination to enhance therapeutic effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using medications that have unsafe interactions with beta blockers or calcium channel blockers.

What evidence supports the effectiveness of the drug diltiazem for myocardial bridging?

Diltiazem, a drug that helps relax blood vessels, has been shown to be effective in treating various heart conditions, such as angina (chest pain) and dilated cardiomyopathy (a type of heart disease). It improves heart function and reduces symptoms, suggesting it may also help with myocardial bridging by improving blood flow and reducing heart strain. ^{1 2 3 4 5}

Is diltiazem generally safe for human use?

Diltiazem is generally considered safe and well-tolerated for treating various heart conditions, with adverse effects occurring in less than 5% of patients. However, in cases of overdose, severe side effects like confusion and low blood pressure can occur, requiring medical intervention. ^{1 6 7 8 9}

How does the drug combination of Diltiazem and Nebivolol work for myocardial bridging?

The combination of Diltiazem and Nebivolol is unique because Diltiazem, a calcium channel blocker, helps relax blood vessels and improve blood flow, while Nebivolol, a beta-blocker with nitric oxide-releasing effects, may help reduce coronary vasospasm. This dual approach could potentially offer a novel way to manage myocardial bridging by addressing both vessel relaxation and spasm reduction. ^{1 2 6 7 10}

Research Team

Jennifer Tremmel, MD, MS

Principal Investigator

Stanford University

Eligibility Criteria

Inclusion Criteria

You are 18 years old or older.

You have stable chest pain that fits specific criteria.

You do not have blockages in your heart arteries, as shown by specific tests.

Exclusion Criteria

A hearing impairment that won't allow for a typical verbal conversation or a visual impairment that won't allow for reading of the written consent

Inability to provide an informed consent, including an inability to speak, read, or understand English or Spanish

Your heart has a lower than normal pumping ability.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized into one of three treatment arms: beta blocker (nebivolol), calcium channel blocker (diltiazem), or placebo for 30 days

4 weeks

1 visit (in-person) at baseline, 1 visit (in-person) at 30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of angina and exercise capacity

6 months

1 visit (in-person) at 6 months

Treatment Details

Interventions

• Diltiazem
• Nebivolol
• Placebo

Participant Groups

Group I: Beta Blocker (nebivolol) Active Control 1 Intervention

Group II: Calcium Channel Blocker (diltiazem) Active Control 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Diltiazem is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Cardizem for:

• Hypertension
• Angina pectoris
• Atrial fibrillation
• Supraventricular tachycardia

Approved in Canada as Dilacor for:

• Hypertension
• Angina pectoris
• Atrial fibrillation
• Supraventricular tachycardia

Approved in European Union as Tiazac for:

• Hypertension
• Angina pectoris
• Atrial fibrillation
• Supraventricular tachycardia

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

In a study of 51 hypertensive patients with vasospastic angina, both nebivolol and diltiazem significantly reduced coronary vasospasm over a 12-week period, but diltiazem was more effective than nebivolol.

Quality of life, as measured by the Seattle Angina Questionnaire, improved for all patients, but there were no significant differences in quality of life or blood pressure changes among the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of nebivolol versus diltiazem in improving coronary artery spasm and quality of life in patients with hypertension and vasospastic angina: A prospective, randomized, double-blind pilot study. Kook, H., Hong, SJ., Yang, KS., et al.[2020]

In a study involving 22 patients with dilated cardiomyopathy, the addition of diltiazem to standard therapy significantly improved survival rates, with no deaths in the diltiazem group over a mean follow-up of 15.4 months, compared to a mean survival of 29 months in historical controls.

Diltiazem treatment also led to a significant increase in left ventricular ejection fraction from 0.34 to 0.44 and improved symptoms according to the New York Heart Association classification, indicating its beneficial effects on heart function and patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Beneficial long-term effects of diltiazem on the course of dilated cardiomyopathy]. Figulla, HR., von Rechenberg, J., Wiegand, V., et al.[2013]

In a study of 30 patients with dilated cardiomyopathy who were not responding well to metoprolol, switching to carvedilol for 12 months led to significant improvements in left ventricular function, including a better ejection fraction and reduced heart size.

While carvedilol showed benefits in heart function and reduced arrhythmias, it negatively impacted exercise capacity, indicating that while it can be effective for heart remodeling, it may not improve overall exercise tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group. Di Lenarda, A., Sabbadini, G., Salvatore, L., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

The use of diltiazem hydrochloride in cardiovascular disorders. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Comparison of nebivolol versus diltiazem in improving coronary artery spasm and quality of life in patients with hypertension and vasospastic angina: A prospective, randomized, double-blind pilot study. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

[Beneficial long-term effects of diltiazem on the course of dilated cardiomyopathy]. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Interventional study of diltiazem in dilated cardiomyopathy: a report of multiple centre clinical trial in China. Chinese Cooperative Group of Diltiazem Intervention Trial in Dilated Cardiomyopathy. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Beneficial effects of long-term diltiazem treatment in dilated cardiomyopathy. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Comparison of the therapeutic effects of the beta-blocking agent bisoprolol and the calcium-blocking agent diltiazem in patients with heart failure due to dilated cardiomyopathy. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Diltiazem. A reappraisal of its pharmacological properties and therapeutic use. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of intravenous diltiazem in patients with atrial fibrillation or atrial flutter. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Delayed presentation of calcium channel antagonist overdose. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group. [2019]