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)

Overview

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.

Interventions

• Other Exercise training
  The training sessions are consist of cycling and as follows: a 10 min warm-up at a light intensity, 20-35 min of cycling exercise in intervals at varying intensities from light (\~60% of max heart rate) to more intensive (80-90% of max heart rate) and ending with 5 min of warm-down at a light intensity. The training intensity will be progressive during the course of the intervention period. The cycling training sessions are supervised . Home training is allowed up to once a week if participants

Primary outcome measures

• Change in Myocardial Blood Flow Reserve (MBFR) [Time frame: From baseline and after 3 months]

Secondary outcome measures (4)

• Change in symptom burden assessed by Seattle Angina Questionnaire [Time frame: From baseline and after 3 months]
• Change in exercise capacity [Time frame: From baseline and after 3 months]
• Change in global rest perfusion in patients with angina symptoms and CMD [Time frame: From baseline and after 3 months]
• Change in global stress perfusion in patients with angina symptoms and CMD [Time frame: From baseline and after 3 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Denmark · 2 centers

• Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57, Frederik — Copenhagen
• Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57 — Frederiksberg

Identifiers

NCT: NCT06529848 · ExINOCA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗