Mechanisms Behind Microvascular Dysfunction in INOCA

NCT06529861 | Not Yet Recruiting DMC

• 1 other identifier: ExINOCA - Part I
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Microvascular Dysfunction; Ischaemia With Non Obstructed Coronary Arteries

Outcome Measures

Primary Outcomes (1)

• Vascular function in response to acetylcholine stress

  Vascular conductance measured by ultrasound doppler during infusion of acetylcholine

  Baseline only

Secondary Outcomes (11)

• Vascular function in response to acetylcholine adenosine stress

  Baseline only

• Myocardial Blood flow reserve

  Baseline only

• Skeletal Muscle Microvascular Function

  Baseline only

• Changes in isolated small artery reactivity assessed with myography

  Baseline only

• Arterial Compliance

  Baseline only

Other Outcomes (2)

• Tone of smooth muscle cells

  Baseline only

• Proteomic and transcriptomic analyses

  Baseline only

Study Arms (2)

Ischemia and no obstructive coronary arteries

patients with angina and reduced myocardial blood flow reserve

Diagnostic Test: [15O]H2O-PET Imaging

Control

controls without angina

Diagnostic Test: [15O]H2O-PET Imaging

Interventions

[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.

Control; Ischemia and no obstructive coronary arteries

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• University of Copenhagen: collaborator

Study Sites (1)

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

Copenhagen, 2400, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample for biobank: A blood sample will be collected for inclusion in a biobank for future research. As part of this process, a distinct patient information and consent form will be administered. Adipose biopsies are assessed in a laboratory at the Biomedical Institute, University of Copenhagen. From these biopsies, segments of small arteries will be promptly dissected free. One segment will be mounted in a myograph for recording of isometric tension (i.e., vasoconstriction and vasodilation) and for histochemical analysis, while the other segment will be snap-frozen for proteomic and histological analysis and the adipose tis-sue/perivascular adipose tissue will be used for genomic and transcriptomic analysis.

Study Officials

• Ylva Hellsten, Professor

  University of Copenhagen

  STUDY CHAIR

Central Study Contacts

Eva Prescott, MD, DMSc

CONTACT

22572614; Eva.Irene.Bossano.Prescott@regionh.dk

Mads Fischer, Ph.D.

CONTACT

24485450; mf@nexs.ku.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD Clinical Professor

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 31, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): May 15, 2028
• Last Updated: July 31, 2024

Record last verified: 2024-07

Locations

DK (1)