The Role of Stem Cells on Immune Cells in the Development of Cardiovascular Diseases (ATHEROSTEM)

Phenotypic and Epigenetic "Trained Immunity" Characteristics of Hematopoietic Stem and Progenitor Cells in Patients With Established Atherosclerosis

An observational pilot proof-of-principle study. 15 patients with significant coronary artery disease and 15 matched controls. To investigate whether long-term activation of the innate immune system, named 'trained innate immunity', occurs at the level of the bone marrow progenitor cells in patients with significant coronary artery disease and whether this correlates with the proinflammatory phenotype of monocytes.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Atherosclerosis

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Department of cardiology, CWZ
    • Nijmegen, Gelderland, Netherlands
      • Department of cardiology, Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

This study will include 15 patients with significant coronary artery disease and 15 patients without significant coronary artery disease. Patients who have been presented to the cardiology departments of the CWZ hospital or Radboud University Medical Centre and have undergone CCTA in the past two years are eligible to participate if they meet the in- and exclusion criteria.

Description

Inclusion Criteria:

• Age ≥18 and ≤75 years
• With or without significant coronary artery disease on CCTA
• Written informed consent

Exclusion Criteria:

• Chronic infections
• Diabetes mellitus
• Medical history of any disease associated with immune deficiency
• Clinically significant infections within 3 months prior to study entry
• Recent hospital admission or surgery with general anaesthesia
• Known chronic kidney or liver disease
• Previous vaccination within 3 months prior to study entry
• Inability to personally provide written informed consent
• Inability to undergo PET-CT scanning
• Chronic use of anti-inflammatory drugs such as NSAIDs
• History of haematological malignant disease
• Documented bleeding diathesis or thrombocytopenia
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Atherosclerosis group; Patients with significant coronary artery disease.
Control group; Healthy controls without confirmed coronary artery disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotypical characteristics of HSPC's	Phenotypical characteristics of HSPC's populations of patients with and without significant coronary artery disease by flowcytometry in percentages.	Study day 2 for patients
Cytokine response of circulating monocytes	Cytokine response of monocytes of patients with and without significant coronary artery disease after 24 hour stimulation with several stimuli measured in cytokine levels.	Study day 2 for patients

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Canisius-Wilhelmina Hospital
• Investigators: Principal Investigator: Niels P. Riksen, MD, PhD, Radboud University Medical Center

Publications and helpful links

General Publications

• Noz MP, Bekkering S, Groh L, Nielen TM, Lamfers EJ, Schlitzer A, El Messaoudi S, van Royen N, Huys EH, Preijers FW, Smeets EM, Aarntzen EH, Zhang B, Li Y, Bremmers ME, van der Velden WJ, Dolstra H, Joosten LA, Gomes ME, Netea MG, Riksen NP. Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease. Elife. 2020 Nov 10;9:e60939. doi: 10.7554/eLife.60939.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: March 31, 2017
• First Submitted That Met QC Criteria: May 29, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): April 1, 2019
• Last Update Submitted That Met QC Criteria: March 29, 2019
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Hematopoietic Stem Cells
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis
• Other Study ID Numbers: NL58806.091.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No