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NCT Number: NCT06529861

Mechanisms Behind Microvascular Dysfunction in INOCA

The purpose of the study is to identify the causes of chest pain in patients experiencing chest pain with no signs of narrowing in the coronary arteries of the heart.

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Key information

Age range

50 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

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

Copenhagen, 2400, Denmark

About this study

A significant number of patients with ischemic heart disease do not exhibit coronary obstruction, leading to their symptoms being attributed to coronary microvascular dysfunction, a condition known as ischemia with no obstructive coronary artery disease (INOCA). Despite a considerable patient population affected by INOCA, the specific mechanisms underlying this microvascular dysfunction 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, an area yet to be explored.

This study aims to identify mechanisms underlying Coronary microvascular dysfunction (CMD) in angina and to assess whether exercise training can improve the condition. In study part I 30 patients with impaired coronary microvascular function and 30 asymptomatic controls will be studied to identify vascular and related molecular mechanisms underlying INOCA by investigating microvascular function in the heart and in cutaneous tissue, skeletal muscle, and adipose tissue.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

Only for angina patients: Have CMD, defined as myocardial bloodflow re-serve (MBFR) < 2.5 or hyperemic myocardial blood flow (hMBF) < 2.3ml/g/min

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 unsuitable candidate for the study.
  • Unable or unwilling to exercise, e.g. due to arthritis or injury*
  • Already are regularly physically active and/or have a maximal oxygen uptake >45 ml/kg/min
  • The subject has a known allergy to either: norepinephrine, adenosine, ketorolac, and or ascorbic acid (vitamin C).

Treatment and study plan

[15O]H2O-PET Imaging

Diagnostic Test

This imaging technique will be used to measure myocardial blood flow (MBF) and myocardial blood flow reserve (MBFR) in patients. The PET-CT scan involves the use of the radioactive tracer [15O]H2O to visualize blood flow in the heart, providing crucial data on coronary microvascular function.

Primary outcomes

  1. Vascular function in response to acetylcholine stress

    Time frame: Baseline only

    Vascular conductance measured by ultrasound doppler during infusion of acetylcholine

Secondary outcomes

  1. Vascular function in response to acetylcholine adenosine stress

    Time frame: Baseline only

    Vascular conductance measured by ultrasound doppler during infusion of Adenosine

  2. Myocardial Blood flow reserve

    Time frame: Baseline only

    Determined by the clinical assessment of [15O]H2O-PET

  3. Skeletal Muscle Microvascular Function

    Time frame: Baseline only

    Evaluated by brachial artery ultrasound Doppler in response to exercise stress to measure blood flow responsiveness in skeletal muscles.

  4. Changes in isolated small artery reactivity assessed with myography

    Time frame: Baseline only

    Analyzed using myograph to study the tone of smooth muscle cells

  5. Arterial Compliance

    Time frame: Baseline only

    Determined by calculations made from intra-arterial pressure and arterial diameter measurements obtained via ultrasound Doppler to assess arterial compliance.

  6. Plasma Lipids

    Time frame: Baseline only

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

  7. Plasma HbA1c

    Time frame: Baseline only

    Conducted through clinical chemical analysis to measure levels of HbA1c in the blood, providing insights into glucose metabolism.

  8. Plasma Levels of Markers Related to Vascular Function

    Time frame: Baseline only

    Assessed using Mesoscale/ELISA to quantify biomarkers associated with vascular function

  9. Plasma Levels of Inflammatory Markers

    Time frame: Baseline only

    Measured using Mesoscale/ELISA/O-Link platforms to evaluate the presence and levels of inflammatory markers

  10. Arterial Blood Pressure

    Time frame: Baseline only

    Monitored with automated blood pressure measurements at rest and during exercise to assess overall cardiovascular health and response to physical activity.

  11. Cardiac Function

    Time frame: Baseline only

    Changes in stroke volume using echocardiography during rest and exercise stress

Other outcomes

  1. Tone of smooth muscle cells

    Time frame: Baseline only

    Changes in isolated small artery reactivity assessed with myography

  2. Proteomic and transcriptomic analyses

    Time frame: Baseline only

    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]

22572614

Mads Fischer, Ph.D.

CONTACT

[email protected]

24485450

Sponsors and collaborators

Lead sponsor

Bispebjerg Hospital

Other

Collaborators

  • University of Copenhagen

Registry information

Official study title

Identification of Mechanisms Behind Microvascular Dysfunction in Ischemia With No Obstructive Coronary Artery Disease

Acronym: ExINOCA-P1

Important dates

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

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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