Clinical trial NCT06529861: Mechanisms Behind Microvascular Dysfunction in INOCA
Official title: Identification of Mechanisms Behind Microvascular Dysfunction in Ischemia With No Obstructive Coronary Artery Disease
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Coronary Microvascular Dysfunction
Ischaemia With Non Obstructed Coronary Arteries
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2024-07-31
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Ischemia with no obstruction of coronary arteries (INOCA) is estimated to affect \>150.000 Danes and the majority are females. These patients have a shorter life expectancy than age matched controls and a higher incidence of major cardiovascular events (1,2).

INOCA is caused by microvascular dysfunction. When there is dysfunction in the microvascu-lature, the blood flow within the coronary vessels fails to increase adequately to meet the de-mand, resulting in ischemia and pain (angina).

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Vascular function in response to acetylcholine stress
timeFrame: Baseline only
Secondary outcomes:
measure: Vascular function in response to acetylcholine adenosine stress
timeFrame: Baseline only
measure: Myocardial Blood flow reserve
timeFrame: Baseline only
measure: Skeletal Muscle Microvascular Function
timeFrame: Baseline only
measure: Changes in isolated small artery reactivity assessed with myography
timeFrame: Baseline only
measure: Arterial Compliance
timeFrame: Baseline only
measure: Plasma Lipids
timeFrame: Baseline only
measure: Plasma HbA1c
timeFrame: Baseline only
measure: Plasma Levels of Markers Related to Vascular Function
timeFrame: Baseline only
measure: Plasma Levels of Inflammatory Markers
timeFrame: Baseline only
measure: Arterial Blood Pressure
timeFrame: Baseline only
measure: Cardiac Function
timeFrame: Baseline only
Other outcomes:
measure: Tone of smooth muscle cells
timeFrame: Baseline only
measure: Proteomic and transcriptomic analyses
timeFrame: Baseline only
Locations:
city: Copenhagen
country: Denmark
facility: Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57, Frederiksberg, Denmark, 2000
Study officials:
affiliation: Department of Nutrition, Exercise and sports, University of Copenhagen
name: Ylva Hellsten, Professor
role: STUDY_CHAIR
References: