Regulation and Signaling of Red Blood Cell (RBC) Endothelial Nitric Oxide Synthase (eNOS) in Patients With Stable and Unstable Coronary Artery Disease

• Sponsor: Heinrich-Heine University, Duesseldorf (Other)
• Overall Status: Completed
• CT.gov ID: NCT02265016
• Collaborator: (none)
• Enrollment: 300
• Location: 1
• Duration (Months): 84
• Patients Per Site Per Month: 3.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Endothelial NO-synthase

Study Design

• Study Type: Observational
• Actual Enrollment: 300 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: Regulation and Signaling of RBC-eNOS in Patients With Stable and Unstable Coronary Artery Disease
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Dec 31, 2020
• Actual Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Patients with CAD Patients with stable coronary artery disease
Patients with ACS Patients with acute coronar syndrome, instable Angina pectoris and low-risk NSTEMI
healthy control group healthy control group without clinical apparent arteriosclerosis

Outcome Measures

Primary Outcome Measures

1. Determination of red cell endothelial nitric oxide-synthase (eNOS)-expression and - activity [baseline, 3 hours and 3 month]

Secondary Outcome Measures

1. Deformability and stability of red blood cell membrane [baseline, 3 hours and 3 month]

   by Laser assisted Optical Rotational Cell Analyzer (LORCA)

2. Microvascular function [baseline, 3 hours and 3 month]

   Determination of microvascular function with Laser-Doppler Perfusion Imaging

3. Peripheral and central hemodynamic measurement [baseline, 3 hours and 3 month]

4. Determination of arterial stiffness [baseline, 3 hours and 3 month]

   Determination of arterial stiffness with pulse wave analysis during blood pressure measurement or echocardiography.

5. determination of flow-mediated dilation [baseline, 3 hours and 3 month]

6. Determination of nitrate and nitrite in blood plasma and red blood cells (RBC) [baseline, 3 hours and 3 month]

7. Determination of nitric oxide and cyclic guanosine monophosphate (cGMP) in blood plasma and in red blood cells [baseline, 3 hours and 3 month]

8. Determination of endothelial microparticles [baseline, 3 hours and 3 month]

9. Electrocardiogram [baseline, 3 hours and 3 month]

10. Aging and turnover of red blood cells [baseline, 3 hours and 3 month]

11. Redox status of red blood cells [baseline, 3 hours and 3 month]

    Determination of redox status of red blood cells will be measured on free thiole with thioltracker and reactive oxygen species( ROS) by dihydrodichlorofluorescein

12. Aggregation of red blood cells [baseline, 3 hours and 3 month]

    Determination of aggregation of red blood cells with LORCA

13. Platelet aggregometry [baseline, 3 hours and 3 month]

14. Expression and function of soluble guanylyl cyclase (sGC) in red blood cells [baseline, 3 hours and 3 month]

    measurement of enzyme expression and activity

15. Expression and activity of Protein Kinase G (PKG) [baseline, 3 hours and 3 month]

    measurement of enzyme expression and activity

16. Determination of leucocyte populations and leucocyte function [baseline, 3 hours and 3 month]

    flow-cytometry

17. Changes of tetrahydrobiopterin-metabolism [baseline, 3 hours and 3 month]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Duesseldorf	Duesseldorf		Germany	40225

Sponsors and Collaborators

• Heinrich-Heine University, Duesseldorf

Investigators

• Principal Investigator: Malte Kelm, Prof. MD, Department of Cardiology, Pneumology and Angiology, University Hospital Duesseldorf

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Klinik für Kardiologie, Pneumologie und Angiologie, Principle Investigator Prof. Dr. Malte Kelm, Heinrich-Heine University, Duesseldorf
• ClinicalTrials.gov Identifier: NCT02265016
• Other Study ID Numbers: RBC in CAD; 13-037
• First Posted: Oct 15, 2014
• Last Update Posted: Feb 16, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Klinik für Kardiologie, Pneumologie und Angiologie, Principle Investigator Prof. Dr. Malte Kelm, Heinrich-Heine University, Duesseldorf: coronary artery disease; acute coronary syndrome; angina pectoris; non-ST-segment elevation myocardial infarction; red blood cells; erythrocytes
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease

Study Results

No Results Posted as of Feb 16, 2021