NCT04321434

Brief Summary

Coronary artery disease (CAD) pathophysiology involves endothelium-dependent (e.g. nitric oxide, acetylcholine) and -independent (e.g. adenosine) vascular dilation impairment, which have been demonstrated at the level of small coronary arteries, medium sized peripheral arteries and subcutaneous microcirculation. Oxygen supplementation, which is frequently overused in clinical settings, seems harmful in acute coronary syndromes and increases microvascular resistance in myocardial and subcutaneous microcirculation through alteration of endothelium-dependent and -independent dilation by an oxidative mechanism. Whether endothelial dysfunction, that is well documented at the level of cardiac microcirculation in CAD patients, is also present at the level of subcutaneous microcirculation is unknown. Also, unknown is whether an acute oxidative stress can be used to probe myocardial microcirculatory dysfunction at the level of subcutaneous microcirculation, which is an easily accessible vascular bed for an in vivo assessment of endothelial-dependent and-independent function. Alterations in cutaneous vascular signalling are evident early in the disease processes. Thus, studying subcutaneous circulation in patients with cardiovascular risk factors could provide vascular information early in CAD processes. This study will test the following 4 hypotheses:

  1. 1.Endothelial dysfunction observed at the level of microvascular cardiac arteries is readily present at the level of subcutaneous microcirculation in a given CAD patient.
  2. 2.An acute oxidative stress such as hyperoxia can be used to test myocardial microcirculatory dysfunction at the level of the more easily accessible subcutaneous microcirculation.
  3. 3.Subcutaneous microcirculation of CAD patients has a lesser vasodilatory response to acetylcholine or sodium nipride than matched healthy subjects. In addition, CAD patients are more prone to dermal vasoconstriction in response to oxygen compared to healthy subjects.
  4. 4.Taken that oxygen is still too often given in excess in most clinical settings, the aim of this study is to rule out possible pitfalls in coronary pressure and resistance determinations in CAD patients receiving unnecessary oxygen supplementation.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Dec 2016

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2016

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 16, 2017

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2018

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2018

Completed
1.5 years until next milestone

First Posted

Study publicly available on registry

March 25, 2020

Completed
Last Updated

March 25, 2020

Status Verified

March 1, 2020

Enrollment Period

1.3 years

First QC Date

January 16, 2017

Last Update Submit

March 24, 2020

Conditions

Coronary Microvascular DiseaseMicrovascular DiseaseIschemic Heart Disease

Keywords

cardiac microvascular dysfunctionsubcutaneous microvascular dysfunctionischemic heart diseaseoxydative stress

Outcome Measures

Primary Outcomes (5)

  • Change from baseline in the acetylcholine-induced skin blood flow after hyperoxia

    Measurement of skin blood flow before, during and after hyperoxia, expressed in perfusion units (arbitrary units).

    1 hour

  • Change from baseline in the sodium nitroprusside-induced skin blood flow after hyperoxia

    Measurement of skin blood flow before, during and after hyperoxia, expressed in perfusion units (arbitrary units).

    1 hour

  • Change from baseline in the heat-induced skin blood flow after hyperoxia

    Measurement of skin blood flow before, during and after hyperoxia, expressed in perfusion units (arbitrary units).

    1 hour

  • Change from Baseline in the index of microcirculatory resistance Under adenosine after hyperoxia

    Measurement of coronary microcirculatory resistance (index of microcirculatory resistance) Under adenosine before and after hyperoxia, expressed in arbitrary units

    10 minutes

  • Change from Baseline in the index of microcirculatory resistance at rest after hyperoxia

    Measurement of coronary microcirculatory resistance (index of microcirculatory resistance) at rest before and after hyperoxia, expressed in arbitrary units

    10 minutes

Study Arms (2)

Hyperoxia

EXPERIMENTAL

* assessment of forearm skin microcirculatory blood flow by laser Doppler perfusion imager at baseline and during hyperemic tests * assessment of coronary microcirculatory blood flow at baseline and during hyperemic tests

Other: HyperoxiaDevice: laser Doppler

Normoxia

PLACEBO COMPARATOR

* assessment of forearm skin microcirculatory blood flow by laser Doppler perfusion imager at baseline and during hyperemic tests * assessment of coronary microcirculatory blood flow at baseline and during hyperemic tests

Other: NormoxiaDevice: laser Doppler

Interventions

HyperoxiaOTHER
Hyperoxia
NormoxiaOTHER
Normoxia
laser DopplerDEVICE

laser Doppler

HyperoxiaNormoxia

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Coronary angiography done in the context of suspicion of coronary artery disease (CAD)

You may not qualify if:

  • Respiratory failure requiring intubation or supplementary oxygen
  • Severe chronic obstructive pulmonary disease
  • Significant arrhythmia precluding waveform analysis (e.g., excessive premature ventricular contractions or atrial fibrillation)
  • Severe valvular heart disease,
  • Suspected elevated central venous pressure (CVP)
  • Heart failure as defined by New York Heart Association class III or IV
  • Previous coronary revascularization or heart transplantation
  • Severe hypertension (systolic pressure \>200 mmHg and diastolic pressure \>120 mmHg at rest)
  • Contraindications to adenosine infusion
  • Contraindication to acetylcholine (Ach) infusion
  • Severe bronchial asthma.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Erasme Hospital

Brussels, Brabant, 1070, Belgium

Location

MeSH Terms

Conditions

Microvascular AnginaMyocardial Ischemia

Interventions

Laser-Doppler Flowmetry

Condition Hierarchy (Ancestors)

Angina PectorisHeart DiseasesCardiovascular DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, CardiovascularDiagnostic Techniques and ProceduresDiagnosisRheologyInvestigative Techniques

Study Officials

  • Jean-Paul Van Vooren, MD, PhD

    Hospital Erasme

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal investigator

Study Record Dates

First Submitted

January 16, 2017

First Posted

March 25, 2020

Study Start

December 1, 2016

Primary Completion

April 1, 2018

Study Completion

October 1, 2018

Last Updated

March 25, 2020

Record last verified: 2020-03

Data Sharing

IPD Sharing
Will not share

Locations

BE(1)