Clinical trial NCT02265016: Regulation and Signaling of Red Blood Cell (RBC) Endothelial Nitric Oxide Synthase (eNOS) in Patients With Stable and Unstable Coronary Artery Disease
Official title: Regulation and Signaling of RBC-eNOS in Patients With Stable and Unstable Coronary Artery Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Endothelial NO-synthase
Keywords: coronary artery disease
acute coronary syndrome
angina pectoris
non-ST-segment elevation myocardial infarction
red blood cells
erythrocytes
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2014-10-15
Enrollment: 300
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: 3 groups:

* ACS group (100 Patients)
* stable CAD group (100 Patients)
* healthy control group (100 Healthy Volunteers)

Brief summary: The aim of this study is measurement of expression and activity of RBC eNOS in different clinical cohorts of patients with coronary artery disease and acute coronary syndrome and to investigate the importance of the NO-stimulated reaction cascade in terms of sGC and PKG.


Eligibility criteria: Inclusion Criteria:

* informed consent
* for ACS(acute coronary syndrome)-Group: angiographic coronary artery disease; acute coronary syndrome, defined by EITHER unstable angina pectoris with significant coronary stenosis (troponin negative, without significant ST-elevation) OR low-risk NSTEMI (Troponin positive, without significant ST-elevation)
* for stable CAD-Group: angiographic coronary artery disease; no acute coronary syndrome within the last 3 months
* healthy control group: No clinical or angiographical signs of apparent atherosclerosis

Exclusion Criteria:

* acute inflammation (CRP \> 1 mg/dl, leukocyte \> 11.000/µl)
* malignant diseases
* pregnancy
* medication with NO-donors ( e.g.isosorbide mononitrate, isosorbide dinitrate, glyceryl trinitrate, Molsidomin, Ranexa)
* patients with STEMI or high-risk NSTEMI

Primary outcomes:
measure: Determination of red cell endothelial nitric oxide-synthase (eNOS)-expression and - activity
timeFrame: baseline, 3 hours and 3 month
Secondary outcomes:
measure: Deformability and stability of red blood cell membrane
timeFrame: baseline, 3 hours and 3 month
measure: Microvascular function
timeFrame: baseline, 3 hours and 3 month
measure: Peripheral and central hemodynamic measurement
timeFrame: baseline, 3 hours and 3 month
measure: Determination of arterial stiffness
timeFrame: baseline, 3 hours and 3 month
measure: determination of flow-mediated dilation
timeFrame: baseline, 3 hours and 3 month
measure: Determination of nitrate and nitrite in blood plasma and red blood cells (RBC)
timeFrame: baseline, 3 hours and 3 month
measure: Determination of nitric oxide and cyclic guanosine monophosphate (cGMP) in blood plasma and in red blood cells
timeFrame: baseline, 3 hours and 3 month
measure: Determination of endothelial microparticles
timeFrame: baseline, 3 hours and 3 month
measure: Electrocardiogram
timeFrame: baseline, 3 hours and 3 month
measure: Aging and turnover of red blood cells
timeFrame: baseline, 3 hours and 3 month
measure: Redox status of red blood cells
timeFrame: baseline, 3 hours and 3 month
measure: Aggregation of red blood cells
timeFrame: baseline, 3 hours and 3 month
measure: Platelet aggregometry
timeFrame: baseline, 3 hours and 3 month
measure: Expression and function of soluble guanylyl cyclase (sGC) in red blood cells
timeFrame: baseline, 3 hours and 3 month
measure: Expression and activity of Protein Kinase G (PKG)
timeFrame: baseline, 3 hours and 3 month
measure: Determination of leucocyte populations and leucocyte function
timeFrame: baseline, 3 hours and 3 month
measure: Changes of tetrahydrobiopterin-metabolism
timeFrame: baseline, 3 hours and 3 month
Other outcomes:
Locations:
city: Duesseldorf
country: Germany
facility: University Hospital Duesseldorf
Study officials:
affiliation: Department of Cardiology, Pneumology and Angiology, University Hospital Duesseldorf
name: Malte Kelm, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: