Impact of Exercise Training on Ischemia With Non-Obstructive Coronary Arteries (INOCA): The ExINOCA Study

Not Applicable

Recruiting

• Conditions: CMD; Coronary Microvascular Disease
• Interventions: Other: Exercise training

• Registration Number: NCT06529848
• Lead Sponsor: Bispebjerg Hospital

Brief Summary

The purpose of the study is to identify causes of chest pain in patients experiencing chest pain with no signs of narrowing of the coronary arteries of the heart, and to investigate whether physical exercise can improve coronary microvascular function.

Hypotheses:

The first hypothesis is that in INOCA, with reduced function of microvasculature of the heart, this reduced function also occurs in other organs of the body.

The second hypothesis is that regular physical activity (aerobic exercise training) can improve coronary microvascular function, reduce symptoms, and that there is a parallel improvement in vascular function in other organs of the body.

Detailed Description

A significant number of patients suspected of chronic coronary syndrome do not have coronary artery obstruction and in a large proportion of these, their symptoms are attributed to coronary microvascular dysfunction (CMD), a condition known as ischemia with no obstructive coronary artery disease (INOCA). Despite a considerable patient population affected by INOCA, the specific mechanisms underlying CMD are not fully understood, often resulting in a lack of targeted treatment. There is evidence to suggest that exercise capacity is linked to coronary microvascular function, positing that exercise training could potentially reverse microvascular dysfunction and address its mechanistic origins, a hypothesis yet to be explored.

This study aims to identify mechanisms underlying CMD in angina and to assess whether exercise training can improve the condition.

The current study is a randomized controlled trial testing the effect of exercise training in patients with CMD. 100 patients will be randomized 1:1 to exercise training or control. The primary outcome is coronary microvascular function, secondary outcomes include symptoms and microvascular function in cutaneous tissue, skeletal muscle, and adipose tissue.

Study Timeline

• Study First Submitted: 2024-07-04
• Study First Submitted QC: 2024-07-29
• Study First Posted: 2024-07-31
• Study Start: 2024-11-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21
• Primary Completion: 2027-10-30
• Study Completion: 2028-05-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Coronary microvascular dysfunction, defined as myocardial bloodflow reserve (MBFR) < 2.5 or hyperemic myocar-dial blood flow (hMBF)<2.3 ml/g/min using [15O]H2O-PET
• No obstructive coronary artery disease

Exclusion Criteria

• Females of childbearing potential (defined as a premeno-pausal female capable of becoming pregnant). The female patient must either be postmenopausal, defined as amen-orrhea for at least 1 year, or surgically sterile
• Heart failure, defined as left ventricular ejection fraction of less than 40%
• Uncontrolled hypertension defined as blood pressure above target 140/90 for all
• Co-morbidity resulting in <1 year expected survival
• Considered by the investigator, for any reason, to be an un-suitable candidate for the study.
• Unable or unwilling to exercise, e.g. due to arthritis or in-jury*
• Already are regularly physically active and/or have a maxi-mal oxygen uptake >45 ml/kg/min

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exercise	Exercise training	The exercise intervention consists of supervised training 40-50 minutes x 3 weekly for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Myocardial Blood Flow Reserve (MBFR)	From baseline and after 3 months	Change in MBFR assessed by \[15O\]H2O-PET-scan

Secondary Outcome Measures

Name	Time	Method
Change in symptom burden assessed by Seattle Angina Questionnaire	From baseline and after 3 months	Seattle angina questionnaire/selfreported (scale range 0-100, 0=poor and 100=excellent health status)
Change in exercise capacity	From baseline and after 3 months	Oxygen uptake during exhaustive exercise
Change in global rest perfusion in patients with angina symptoms and CMD	From baseline and after 3 months	Change in Myocardial Blood Flow assessed by \[15O\]H2O-PET-scan
Change in global stress perfusion in patients with angina symptoms and CMD	From baseline and after 3 months	Change in hyperemic Myocardial Blood Flow assessed by \[15O\]H2O-PET-scan

Trial Locations

Locations (2)

Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57, Frederiksberg, Denmark, 2000; 🇩🇰 Copenhagen, Denmark

Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57; 🇩🇰 Frederiksberg, Denmark