ANOCA - Angina With Non-obstructive Coronary ArteriesNEO-NOCADNCT07422818
Non-invasive Evaluation of Patients With Angina and Non-obstructive Coronary Artery Disease
A study testing Coronary flow reserve assessed by Echocardiography in people with ANOCA - Angina With Non-obstructive Coronary Arteries, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
Trial summary
This is a single-center, prospective interventional study evaluating noninvasive coronary function testing using transthoracic Doppler echocardiography of the left anterior descending coronary artery in patients with stable angina and nonobstructive coronary artery disease (ANOCA) who previously underwent invasive… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- ANOCA - Angina With Non-obstructive Coronary Arteries
- What is being tested?
- Coronary flow reserve assessed by Echocardiography
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- No sites listed yet
- Study dates
- Mar 2026to Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 18 and 90 years;
- ICA performed within the previous 12 months from enrollment and characterized by: (a) absence of obstructive CAD (\<50% diameter reduction or FFR by \>0.80); (b) invasive assessment of epicardial/microvascular spasm by acetylcholine test;
- Signed informed consent.
Who cannot join
- Presentation as an acute coronary syndrome (i.e. unstable chest pain) or a typical history of variant angina (frequent angina pain at rest with ST-segment elevation at the ECG, caused by recurrent coronary spasm);
- Previous coronary revascularization with surgical intervention;
- Asthma or known intolerance or contraindications to dipyridamole;
- Serious medical conditions, including renal failure (eGFR \<30 mL/min), liver diseases, malignancies, and acute or chronic inflammatory diseases;
- Pregnancy;
- Psychological conditions that might hamper patient co-operation;
- Any condition that, in the judgment of the investigators, would make difficult for the patient to complete the study protocol;
- Missed informed consent.
About this study
This is a single-center, prospective interventional study evaluating noninvasive coronary function testing using transthoracic Doppler echocardiography of the left anterior descending coronary artery in patients with stable angina and nonobstructive coronary artery disease (ANOCA) who previously underwent invasive coronary function testing (adenosine and/or acetylcholine).
A group of age- and sex-matched healthy volunteers will be enrolled to support interpretation of potentially abnormal noninvasive responses observed in patients.
Read the detailed description
Patients referred to the catheterization laboratory of Fondazione Policlinico Universitario A. Gemelli IRCCS for stable angina who show non-obstructive coronary artery disease at invasive coronary angiography and underwent invasive coronary function testing will be enrolled.
During a transthoracic echocardiographic Doppler examination of the left anterior descending coronary artery, participants will undergo three standardized stimuli (hyperventilation, cold pressor test, and dipyridamole) separated by 30-minute intervals, with peak diastolic velocity measured at baseline and at the end of each test.
For each stimulus, the coronary blood flow velocity response will be expressed as the ratio between peak and basal peak diastolic velocity.
Participants will also complete the Seattle Angina Questionnaire to assess symptom burden.
The primary aim of the study is to investigate the usefulness of studying coronary flow reserve by transthoracic color Doppler echocardiogram in reaching the diagnosis of microcirculation dysfunction and/or coronary vasomotor disturbance.
The secondary aim of the study was to assess whether abnormalities on the stress echocardiogram with dipyridamole, hyperventilation, and cold-pressor test are related to the patient's symptoms.
- Being tested
- Coronary flow reserve assessed by Echocardiography
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coronary flow reserve assessed by EchocardiographyDiagnostic test
All patients and controls will undergo the following tests during transthoracic echocardiographic Doppler examination of the left anterior descending coronary artery, with time intervals of 30 minutes from each other:
- hyperventilation test: the patient is asked to breathe at a rate of 30 respirations per minute, for 5 minutes;
- cold pressor test: the patient puts his/her right hand in ice water for 2 minutes;
- dipyridamole test: intravenous dipyridamole is administered at a dose of 0.84 mg/kg over 6 minutes; Peak diastolic velocity (PDV) of blood flow in the left anterior descending coronary artery will be measured before and at the end of each test by pulsed-wave Doppler, using a GE E95 echocardiographic machine.
The ratio between peak flow velocity of coronary blood flow at peak of each test and the relative basal peak flow velocity of coronary blood flow is taken as the response of coronary blood flow velocity to each test.
| Study group | Role | What they receive |
|---|---|---|
| Non-invasive coronary flow reserve in patients with ANOCA | Experimental | We will enroll patients referred to the catheterization laboratory of the Fondazione Policlinico Universitario A. Gemelli IRCCS for stable angina who showed non-obstructive coronary arteries at coronary angiography and underwent invasive coronary functional tests (adenosine and/or acetylcholine test). Receives: Diagnostic Test: Coronary flow reserve assessed by Echocardiography |
| Non-invasive coronary flow reserve in healthy volunteers | Active comparator | To confirm the reliability of possible abnormal results of non-invasive coronary functional tests in angina and non-obstructive coronary arteries (ANOCA) patients, we will enroll healthy control subjects of similar age and gender of enrolled patients, selected among those referred to our ambulatory of clinical visits for a routine cardiological evaluation and undergo a screening stress test for coronary artery disease. They will undergo a dipyridamole stress echocardiogram, which is commonly used in clinical practice to investigate the presence of coronary artery disease. Receives: Diagnostic Test: Coronary flow reserve assessed by Echocardiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation (Phi coefficient) between TTE-induced vasoconstriction and acetylcholine-induced spasm at invasive assessment.
The primary aim of the study is to investigate the usefulness of studying coronary flow reserve by transthoracic color Doppler echocardiogram in reaching the diagnosis of coronary vasomotor disturbance.
Measured: Periprocedural
Secondary outcomes (3)
Agreement between dipyridamole-induced non-invasive coronary flow reserve and invasive coronary flow reserve
Agreement between coronary flow reserve (CFR) measured by transthoracic echocardiography during dipyridamole stress and CFR measured during invasive coronary function testing.
Unit of Measure: Pearson correlation coefficient
Measured: Periprocedural
Agreement between cold pressor test-induced non-invasive coronary flow reserve and invasive coronary flow reserve
Agreement between coronary flow reserve (CFR) measured by transthoracic echocardiography during cold pressor test and CFR measured during invasive coronary function testing.
Unit of Measure: Pearson correlation coefficient
Measured: Periprocedural
Association between abnormal non-invasive coronary vasomotor response and angina symptoms
Comparison of Seattle Angina Questionnaire (SAQ) summary score between patients with abnormal versus normal coronary vasodilator response during stress echocardiography.
Unit of Measure: SAQ summary score (0-100)
Measured: Periprocedural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study startMar 2026 (estimated)
- Primary completionOct 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ANOCA - Angina With Non-obstructive Coronary ArteriesStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07422818
- Sponsor's protocol ID
- 7363
- Acronym
- NEO-NOCAD
- Status last verified
- Jan 2026
- First submitted
- 21 Jan 2026
- Last updated
- 20 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Evaluation of Patients With Angina and Non-obstructive Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT07422818
- Acronym / sponsor ID
- NEO-NOCAD / 7363
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- Mar 2026 (estimated)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 20 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-center, prospective interventional study evaluating noninvasive coronary function testing using transthoracic Doppler echocardiography of the left anterior descending coronary artery in patients with stable angina and nonobstructive coronary artery disease (ANOCA) who previously underwent invasive coronary function testing (adenosine and/or acetylcholine).
A group of age- and sex-matched healthy volunteers will be enrolled to support interpretation of potentially abnormal noninvasive responses observed in patients.
Detailed description
Patients referred to the catheterization laboratory of Fondazione Policlinico Universitario A. Gemelli IRCCS for stable angina who show non-obstructive coronary artery disease at invasive coronary angiography and underwent invasive coronary function testing will be enrolled.
During a transthoracic echocardiographic Doppler examination of the left anterior descending coronary artery, participants will undergo three standardized stimuli (hyperventilation, cold pressor test, and dipyridamole) separated by 30-minute intervals, with peak diastolic velocity measured at baseline and at the end of each test.
For each stimulus, the coronary blood flow velocity response will be expressed as the ratio between peak and basal peak diastolic velocity.
Participants will also complete the Seattle Angina Questionnaire to assess symptom burden.
The primary aim of the study is to investigate the usefulness of studying coronary flow reserve by transthoracic color Doppler echocardiogram in reaching the diagnosis of microcirculation dysfunction and/or coronary vasomotor disturbance.
The secondary aim of the study was to assess whether abnormalities on the stress echocardiogram with dipyridamole, hyperventilation, and cold-pressor test are related to the patient's symptoms.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-invasive coronary flow reserve in patients with ANOCA | Experimental | Diagnostic Test: Coronary flow reserve assessed by EchocardiographyWe will enroll patients referred to the catheterization laboratory of the Fondazione Policlinico Universitario A. Gemelli IRCCS for stable angina who showed non-obstructive coronary arteries at coronary angiography and underwent invasive coronary functional tests (adenosine and/or acetylcholine test). |
| Non-invasive coronary flow reserve in healthy volunteers | Active comparator | Diagnostic Test: Coronary flow reserve assessed by EchocardiographyTo confirm the reliability of possible abnormal results of non-invasive coronary functional tests in angina and non-obstructive coronary arteries (ANOCA) patients, we will enroll healthy control subjects of similar age and gender of enrolled patients, selected among those referred to our ambulatory of clinical visits for a routine cardiological evaluation and undergo a screening stress test for coronary artery disease. They will undergo a dipyridamole stress echocardiogram, which is commonly used in clinical practice to investigate the presence of coronary artery disease. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age between 18 and 90 years;
- ICA performed within the previous 12 months from enrollment and characterized by: (a) absence of obstructive CAD (\<50% diameter reduction or FFR by \>0.80); (b) invasive assessment of epicardial/microvascular spasm by acetylcholine test;
- Signed informed consent.
Key exclusion criteria (8 listed)
- Presentation as an acute coronary syndrome (i.e. unstable chest pain) or a typical history of variant angina (frequent angina pain at rest with ST-segment elevation at the ECG, caused by recurrent coronary spasm);
- Previous coronary revascularization with surgical intervention;
- Asthma or known intolerance or contraindications to dipyridamole;
- Serious medical conditions, including renal failure (eGFR \<30 mL/min), liver diseases, malignancies, and acute or chronic inflammatory diseases;
- Pregnancy;
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 |
|---|---|---|
| Coronary flow reserve assessed by EchocardiographyAll patients and controls will undergo the following tests during transthoracic echocardiographic Doppler examination of the left anterior descending coronary artery, with time intervals of 30 minutes from each other: 1. hyperventilation test: the patient is asked to breathe at a rate of 30 respirations per minute, for 5 minutes; 2. cold pressor test: the patient puts his/her right hand in ice water for 2 minutes; 3. dipyridamole test: intravenous dipyridamole is administered at a dose of 0.84 mg/kg over 6 minutes; Peak diastolic velocity (PDV) of blood flow in the left anterior descending coronary artery will be measured before and at the end of each test by pulsed-wave Doppler, using a GE E95 echocardiographic machine. The ratio between peak flow velocity of coronary blood flow at peak of each test and the relative basal peak flow velocity of coronary blood flow is taken as the response of coronary blood flow velocity to each test. | Diagnostic test | Non-invasive coronary flow reserve in healthy volunteers, Non-invasive coronary flow reserve in patients with ANOCA |
Primary outcome
Correlation (Phi coefficient) between TTE-induced vasoconstriction and acetylcholine-induced spasm at invasive assessment.
Time frame: Periprocedural
The primary aim of the study is to investigate the usefulness of studying coronary flow reserve by transthoracic color Doppler echocardiogram in reaching the diagnosis of coronary vasomotor disturbance.
3 secondary outcomes
Agreement between dipyridamole-induced non-invasive coronary flow reserve and invasive coronary flow reserve
Time frame: Periprocedural
Agreement between cold pressor test-induced non-invasive coronary flow reserve and invasive coronary flow reserve
Time frame: Periprocedural
Association between abnormal non-invasive coronary vasomotor response and angina symptoms
Time frame: Periprocedural
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Coronary flow reserve assessed by Echocardiography in people with ANOCA - Angina With Non-obstructive Coronary Arteries, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
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 3 inclusion and 8 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: opening soon, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
This study is still under way. Results are not available in the source record yet.
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?
Correlation (Phi coefficient) between TTE-induced vasoconstriction and acetylcholine-induced spasm at invasive assessment. (time frame: Periprocedural). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Feb 2026; AzTrials last refreshed its copy on 7 Nov 2026.