Myocardial BridgingPhase 2NCT04130438
Efficacy of Medical Therapy in Women and Men With Angina and Myocardial Bridging
A Phase 2 study testing Nebivolol and Diltiazem in people with Myocardial Bridging, run by Stanford University at 1 site in United States.
Trial summary
The proposed clinical trial is relevant to public health because it is expected to expand the differential diagnosis and provide an evidence--based therapy for the large population of patients with angina in the absence of obstructive CAD who currently remain undiagnosed and untreated. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myocardial Bridging
- What is being tested?
- Nebivolol and Diltiazem
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2020to 17 Oct 2024
- Phase
- Phase 2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Stable angina (typical or atypical, based on Diamond criteria (35))
- Exercise stress echocardiogram or exercise stress test (with beta blocker or calcium channel blocker held) performed within six months of enrollment
- CCTA or invasive coronary angiogram confirming the presence of an MB
- Absence of obstructive CAD, as demonstrated by no ischemia on stress testing and no significant obstructive CAD (coronary stenosis <50%) on CCTA or invasive coronary angiogram
Who cannot join
- Asymptomatic
- Status--post heart transplant
- Presence of another likely explanation of chest pain, such as pulmonary hypertension, hypertrophic obstructive cardiomyopathy, or aortic stenosis
- Presence of an acute coronary syndrome (unstable angina, NSTEMI, or STEMI), Tako--tsubo, or cardiogenic shock
- An abnormal left ventricular ejection fraction (EF<55%)
- History of a severe adverse reaction to beta blockers or calcium channel blockers (prior minor intolerance or ineffectiveness not exclusion)
Show all 12Show fewer
- Use of existing medication that has an unsafe drug--drug interaction with beta blockers or calcium channel blockers
- Refusal to take beta blockers or calcium channel blockers
- Resting systolic blood pressure <100 mmHg or heart rate <50 beats per minute
- Inability to provide an informed consent, including an inability to speak, read, or understand English or Spanish
- 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
- A potentially vulnerable subject (including pregnant women, prisoners, economically and educationally disadvantaged, decisionally impaired, and institutionalized individuals)
Trial locations and contacts
1 site in 1 country.
About this study
The proposed clinical trial is relevant to public health because it is expected to expand the differential diagnosis and provide an evidence--based therapy for the large population of patients with angina in the absence of obstructive CAD who currently remain undiagnosed and untreated. It, therefore, upholds an important part of the mission of the The National Heart, Lung, and Blood Institute (NHLBI), which is to promote the treatment of heart disease and enhance the health of all individuals so that they can live longer and more fulfilling lives.
Read the detailed description
Angina in the absence of obstructive coronary artery disease (CAD) affects millions, resulting in a reduced quality of life and a burden on the health care system. Previous work has focused on endothelial and microvascular dysfunction as causes of angina in these patients, but even when these etiologies are tested for, nearly half of patients remain undiagnosed, and proven therapies are lacking. The long--term goal of this research proposal is to improve the lives of patients with angina in the absence of obstructive CAD. These patients have been found to have a disproportionate prevalence of myocardial bridges (MBs) (60% vs. 30% in the general population).
MBs are known to cause angina, and the mechanism by which they do so is also known, but MBs have not been actively studied in the context of patients with angina in the absence of obstructive CAD. Medical therapies for symptomatic MBs, including beta blockers and calcium channel blocker have been suggested, but have never been appropriately tested, and may not be better than placebo. The overall objective of this research proposal is to demonstrate that MBs are an important and treatable cause of angina in patients with non--obstructive CAD.
The investigator will conduct the first--ever randomized, double--blind, placebo--controlled trial of medical therapy in patients with angina and an MB. The rationale is that a proven treatment would significantly expand the paradigm by which patients with angina in the absence of obstructive CAD are evaluated and treated. Our central hypothesis is that beta blockers and calcium channel blockers are effective treatments for reducing angina in patients with an MB compared with placebo. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Determine the efficacy of beta blockers and calcium channel blockers in treating patients with angina and an MB and 2) Identify predictors of efficacy of beta blockers and calcium channel blockers in treating patients with angina and an MB. For Aim #1, the investigator will randomize a total of 360 adult patients with angina and an MB into one of three treatment arms: beta blocker (nebivolol), calcium channel blocker (diltiazem), or placebo (1:1:1).
Efficacy will be determined after 30 days on the study drug by a change in angina, as assessed by the Seattle Angina Questionnaire (SAQ). The investigator will also evaluate changes in exercise capacity, as well as drug adherence and side effects. For Aim #2, the investigator will evaluate MB muscle index (MMI, a product of MB length x depth) by coronary computed tomography angiography, as well as male sex, as predictors of efficacy. Randomization will be stratified on sex, ensuring a balance of women and men in each arm. The proposed research is innovative because it shifts the current clinical perspective on angina in the absence of obstructive CAD by considering myocardial bridging as a potential etiology.
It is also significant because it will substantially increase the number of patients with angina in the absence of obstructive CAD that clinicians are able to diagnose and treat, ultimately leading to improvements in quality of life and a reduction in health care costs.
- Conditions
- Myocardial Bridging
- Being tested
- Nebivolol, Diltiazem, Placebo
- Medical subject headings
- Myocardial Bridging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NebivololDrug
The intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days.
DiltiazemDrug
The intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days.
PlaceboOther
The intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days.
| Study group | Role | What they receive |
|---|---|---|
| Beta Blocker (nebivolol) | Active comparator | Not described Receives: Drug: Nebivolol |
| Calcium Channel Blocker (diltiazem) | Active comparator | Not described Receives: Drug: Diltiazem |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Angina Score Assessed by the Seattle Angina Questionnaire (SAQ)
Effectiveness of beta blockers and calcium channel blockers for reducing angina in patients with a Myocardial Bridge (MB) compared to placebo determined after 30 days on the study drug by a change in angina, as assessed by the Seattle Angina Questionnaire (SAQ). The SAQ assesses 5 domains: physical limitation, angina stability angina frequency, treatment satisfaction, and quality of life. Each domain score is normalized to a range of 0 to 100, with higher scores corresponding to better outcomes.
Measured: baseline and 30 days
Secondary outcomes (6)
Duke Treadmill Score by Risk Category
Changes in exercise capacity will be measured by difference in exercise time increment between the groups. The Duke treadmill score is calculated as exercise time × (5 × ST-segment deviation) - (4 × exercise angina), with 0 = no angina, 1 = non-limiting angina, and 2 = exercise-limiting angina. Possible scores range from -25 (highest risk) to +15 (lowest risk). Scores are reported by the number of participants in each risk category: low risk (≥+5), moderate risk (-10 to +4) and high risk (≤-11) (Shaw, et al, 1998).
Measured: baseline, 30 days
Duke Treadmill Score
The Duke treadmill score is calculated as exercise time × (5 × ST-segment deviation) - (4 × exercise angina), with 0 = no angina, 1 = non-limiting angina, and 2 = exercise-limiting angina. Possible scores range from -25 (highest risk) to +15 (lowest risk).
Measured: baseline, 30 days
Number of Participants With Cardiac Events
Major adverse cardiovascular events include death, heart attack, coronary stent or bypass surgery, and stroke.
Measured: 30 days, 6 months
Drug Adherence.
Percentage of drug taken by participants, measured by pill count at the end of 30 days.
Measured: 30 days
Number of Participants With Side Effects
Patient self-reported side effects recorded in a diary to be turned in at 30 days. In addition, patients are requested to contact us regarding any serious side effects during the study. Finally, patients are asked about any side effects they experienced during their 30-day follow-up to ensure that symptoms are captured.
Measured: 30 days
Treatment Course
Number of participants who stayed on the study drug at the initial dose, stayed on the study drug at a different dose, switched to an alternate therapy, and/or underwent further cardiac testing.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2019
- Study start15 Oct 2020
- Primary completion11 Mar 2022
- Study completion17 Oct 2024
Why it stopped: Low recruitment, insufficient funding
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 (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial BridgingStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer A Tremmel, MD, MS, Stanford University
- Investigators
- Jennifer Tremmel, MD, MS, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04130438
- Sponsor's protocol ID
- 47447
- Status last verified
- Feb 2025
- First submitted
- 1 Apr 2019
- Last updated
- 25 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shaw LJ, Peterson ED, Shaw LK, Kesler KL, DeLong ER, Harrell FE Jr, Muhlbaier LH, Mark DB. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation. 1998 Oct 20;98(16):1622-30. doi: 10.1161/01.cir.98.16.1622.
PubMed 9778327
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Medical Therapy in Women and Men With Angina and Myocardial Bridging
- ClinicalTrials.gov ID
- NCT04130438
- Acronym / sponsor ID
- 47447
- Conditions
- Myocardial Bridging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment, insufficient funding
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 15 Oct 2020 (actual)
- Primary completion
- 11 Mar 2022 (actual)
- Study completion
- 17 Oct 2024 (actual)
- First posted
- 17 Oct 2019 (actual)
- Results
- Posted 25 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed clinical trial is relevant to public health because it is expected to expand the differential diagnosis and provide an evidence--based therapy for the large population of patients with angina in the absence of obstructive CAD who currently remain undiagnosed and untreated. It, therefore, upholds an important part of the mission of the The National Heart, Lung, and Blood Institute (NHLBI), which is to promote the treatment of heart disease and enhance the health of all individuals so that they can live longer and more fulfilling lives.
Detailed description
Angina in the absence of obstructive coronary artery disease (CAD) affects millions, resulting in a reduced quality of life and a burden on the health care system. Previous work has focused on endothelial and microvascular dysfunction as causes of angina in these patients, but even when these etiologies are tested for, nearly half of patients remain undiagnosed, and proven therapies are lacking. The long--term goal of this research proposal is to improve the lives of patients with angina in the absence of obstructive CAD. These patients have been found to have a disproportionate prevalence of myocardial bridges (MBs) (60% vs. 30% in the general population).
MBs are known to cause angina, and the mechanism by which they do so is also known, but MBs have not been actively studied in the context of patients with angina in the absence of obstructive CAD. Medical therapies for symptomatic MBs, including beta blockers and calcium channel blocker have been suggested, but have never been appropriately tested, and may not be better than placebo. The overall objective of this research proposal is to demonstrate that MBs are an important and treatable cause of angina in patients with non--obstructive CAD.
The investigator will conduct the first--ever randomized, double--blind, placebo--controlled trial of medical therapy in patients with angina and an MB. The rationale is that a proven treatment would significantly expand the paradigm by which patients with angina in the absence of obstructive CAD are evaluated and treated. Our central hypothesis is that beta blockers and calcium channel blockers are effective treatments for reducing angina in patients with an MB compared with placebo. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Determine the efficacy of beta blockers and calcium channel blockers in treating patients with angina and an MB and 2) Identify predictors of efficacy of beta blockers and calcium channel blockers in treating patients with angina and an MB. For Aim #1, the investigator will randomize a total of 360 adult patients with angina and an MB into one of three treatment arms: beta blocker (nebivolol), calcium channel blocker (diltiazem), or placebo (1:1:1).
Efficacy will be determined after 30 days on the study drug by a change in angina, as assessed by the Seattle Angina Questionnaire (SAQ). The investigator will also evaluate changes in exercise capacity, as well as drug adherence and side effects. For Aim #2, the investigator will evaluate MB muscle index (MMI, a product of MB length x depth) by coronary computed tomography angiography, as well as male sex, as predictors of efficacy. Randomization will be stratified on sex, ensuring a balance of women and men in each arm. The proposed research is innovative because it shifts the current clinical perspective on angina in the absence of obstructive CAD by considering myocardial bridging as a potential etiology.
It is also significant because it will substantially increase the number of patients with angina in the absence of obstructive CAD that clinicians are able to diagnose and treat, ultimately leading to improvements in quality of life and a reduction in health care costs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Beta Blocker (nebivolol) | Active comparator | Drug: Nebivolol |
| Calcium Channel Blocker (diltiazem) | Active comparator | Drug: Diltiazem |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥18 years
- Stable angina (typical or atypical, based on Diamond criteria (35))
- Exercise stress echocardiogram or exercise stress test (with beta blocker or calcium channel blocker held) performed within six months of enrollment
- CCTA or invasive coronary angiogram confirming the presence of an MB
- Absence of obstructive CAD, as demonstrated by no ischemia on stress testing and no significant obstructive CAD (coronary stenosis <50%) on CCTA or invasive coronary angiogram
Key exclusion criteria (12 listed)
- Asymptomatic
- Status--post heart transplant
- Presence of another likely explanation of chest pain, such as pulmonary hypertension, hypertrophic obstructive cardiomyopathy, or aortic stenosis
- Presence of an acute coronary syndrome (unstable angina, NSTEMI, or STEMI), Tako--tsubo, or cardiogenic shock
- An abnormal left ventricular ejection fraction (EF<55%)
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 |
|---|---|---|
| NebivololThe intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days. | Drug | Beta Blocker (nebivolol) |
| DiltiazemThe intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days. | Drug | Calcium Channel Blocker (diltiazem) |
| PlaceboThe intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days. | Other | Placebo |
Primary outcome
Change in Angina Score Assessed by the Seattle Angina Questionnaire (SAQ)
Time frame: baseline and 30 days
Effectiveness of beta blockers and calcium channel blockers for reducing angina in patients with a Myocardial Bridge (MB) compared to placebo determined after 30 days on the study drug by a change in angina, as assessed by the Seattle Angina Questionnaire (SAQ). The SAQ assesses 5 domains: physical limitation, angina stability angina frequency, treatment satisfaction, and quality of life. Each domain score is normalized to a range of 0 to 100, with higher scores corresponding to better outcomes.
6 secondary outcomes
Duke Treadmill Score by Risk Category
Time frame: baseline, 30 days
Duke Treadmill Score
Time frame: baseline, 30 days
Number of Participants With Cardiac Events
Time frame: 30 days, 6 months
Drug Adherence.
Time frame: 30 days
Number of Participants With Side Effects
Time frame: 30 days
Treatment Course
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9778327Shaw LJ, Peterson ED, Shaw LK, Kesler KL, DeLong ER, Harrell FE Jr, Muhlbaier LH, Mark DB. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation. 1998 Oct 20;98(16):1622-30. doi: 10.1161/01.cir.98.16.1622.
- Individual participant dataSharing planned: No
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Coronary Myocardial Bridge and Coronary Plaques on MDCT
Myocardial Bridging, Coronary Atherosclerosis
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Minimally Invasive Coronary Artery Bypass Supported by Cangrelor
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Recruiting
Myocardialbridge Bypass Graft Surgery Efficacy Verification
Myocardial Bridge of Coronary Artery, Myocardial Bridge
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Efficacy of Targeted Medical Therapy in Angina and Nonobstructive Coronary Arteries
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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.
Jennifer Tremmel, MD, MS principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nebivolol and Diltiazem in people with Myocardial Bridging, run by Stanford University 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 5 inclusion and 12 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 25 Feb 2025. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 25 Feb 2025). 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?
Change in Angina Score Assessed by the Seattle Angina Questionnaire (SAQ) (time frame: baseline and 30 days). 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 NCT04130438, which also lists 1 linked publication.
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 25 Feb 2025.