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NCT Number: NCT06529848

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

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.

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Key information

Conditions

Coronary Microvascular Disease Angina Pectoris CMD Cardiovascular Diseases Heart Diseases Microvascular Angina Myocardial Ischemia Vascular Diseases

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Exercise training

Other

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 are able to adhere to the prescribed intensity levels.

Training sessions are closely monitored to ensure effectiveness and safety. This includes heart rate monitoring, perceived exertion assessment.

Other names: Physical activity, Endurance training

Primary outcomes

  1. Change in Myocardial Blood Flow Reserve (MBFR)

    Time frame: From baseline and after 3 months

    Change in MBFR assessed by [15O]H2O-PET-scan

Secondary outcomes

  1. Change in symptom burden assessed by Seattle Angina Questionnaire

    Time frame: From baseline and after 3 months

    Seattle angina questionnaire/selfreported (scale range 0-100, 0=poor and 100=excellent health status)

  2. Change in exercise capacity

    Time frame: From baseline and after 3 months

    Oxygen uptake during exhaustive exercise

  3. Change in global rest perfusion in patients with angina symptoms and CMD

    Time frame: From baseline and after 3 months

    Change in Myocardial Blood Flow assessed by [15O]H2O-PET-scan

  4. Change in global stress perfusion in patients with angina symptoms and CMD

    Time frame: From baseline and after 3 months

    Change in hyperemic Myocardial Blood Flow assessed by [15O]H2O-PET-scan

Other outcomes

  1. Vascular Function Adaptations

    Time frame: From baseline and after 3 months

    Changes in Arterial compliance (C = ΔV/ ΔP) calculated from intraarterial pressure ΔP and arterial diameter (ΔD) measured by ultrasound Doppler

  2. Changes in skin microvascular function

    Time frame: From baseline and after 3 months

    Hand microcirculatory blood flow assessed by Laser Speckle Contrast Imaging

  3. Change in plasma levels of markers related to vascular function

    Time frame: From baseline and after 3 months

    Plasma levels of markers related to vascular function assessed by Mesoscale/ELISA

  4. Changes in Arterial Blood Pressure

    Time frame: From baseline and after 3 months

    Assessed by automated blood pressure at rest

  5. Change in plasma Lipids

    Time frame: From baseline and after 3 months

    Conducted through clinical chemical analysis to measure levels of HDL, and triglycerides in the blood, providing insights into lipid profiles.

  6. Changes in Plasma Levels of Inflammatory Markers

    Time frame: From baseline and after 3 months

    Measured using Mesoscale/ELISA/O-Link platforms to evaluate the presence and levels of inflammatory markers, indicating systemic inflammation.

  7. Proteomic and transcriptomic analyses

    Time frame: From baseline and after 3 months

    Changes in gene and protein expressions patterns in small arteries

Study contacts

Contact information is provided by the study sponsor or research team.

Eva Prescott, MD, DMSc

CONTACT

[email protected]

004522572614

Mads Fischer, MSc

CONTACT

[email protected]

+45 23 46 36 66

Sponsors and collaborators

Lead sponsor

Bispebjerg Hospital

Other

Collaborators

  • University of Copenhagen

Registry information

Official study title

Ischemia With No Obstruction of Coronary Arteries: Underlying Mechanisms and the Impact of Exercise Training (EXINOCA)

Acronym: ExINOCA

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Jul 31, 2024
Registry last updated
Feb 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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