Clinical trial NCT06529848: Impact of Exercise Training on Ischemia With Non-Obstructive Coronary Arteries (INOCA): The ExINOCA Study
Official title: Ischemia With No Obstruction of Coronary Arteries: Underlying Mechanisms and the Impact of Exercise Training (EXINOCA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Microvascular Disease
CMD
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2024-07-31
Enrollment: 100
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial in which 100 angina patients with reduced flow reserve (INOCA patients) are randomized 1:1 to either exercise training or control (no exer-cise training).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Myocardial Blood Flow Reserve (MBFR)
timeFrame: From baseline and after 3 months
Secondary outcomes:
measure: Change in symptom burden assessed by Seattle Angina Questionnaire
timeFrame: From baseline and after 3 months
measure: Change in exercise capacity
timeFrame: From baseline and after 3 months
measure: Change in global rest perfusion in patients with angina symptoms and CMD
timeFrame: From baseline and after 3 months
measure: Change in global stress perfusion in patients with angina symptoms and CMD
timeFrame: From baseline and after 3 months
Other outcomes:
measure: Vascular Function Adaptations
timeFrame: From baseline and after 3 months
measure: Changes in skin microvascular function
timeFrame: From baseline and after 3 months
measure: Change in plasma levels of markers related to vascular function
timeFrame: From baseline and after 3 months
measure: Changes in Arterial Blood Pressure
timeFrame: From baseline and after 3 months
measure: Change in plasma Lipids
timeFrame: From baseline and after 3 months
measure: Changes in Plasma Levels of Inflammatory Markers
timeFrame: From baseline and after 3 months
measure: Proteomic and transcriptomic analyses
timeFrame: From baseline and after 3 months
Locations:
city: Copenhagen
country: Denmark
facility: Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57, Frederiksberg, Denmark, 2000
city: Frederiksberg
country: Denmark
facility: Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57
Study officials:
affiliation: Department of Nutrition, Exercise and sports, University of Copenhagen
name: Eva Prescott, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Nutrition, Exercise and sports, University of Copenhagen
name: Ylva Hellsten
role: PRINCIPAL_INVESTIGATOR
References: