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

• ClinicalTrials.gov Identifier: NCT03172507
• Recruitment Status: Completed
• First Posted: June 1, 2017
• Last Update Posted: April 1, 2019
• Sponsor: Radboud University Medical Center
• Collaborator: Canisius-Wilhelmina Hospital
• Information provided by (Responsible Party): Radboud University Medical Center

Tracking Information

• First Submitted Date: March 31, 2017
• First Posted Date: June 1, 2017
• Last Update Posted Date: April 1, 2019
• Actual Study Start Date: September 20, 2017
• Actual Primary Completion Date: August 31, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 29, 2017)

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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Role of Stem Cells on Immune Cells in the Development of Cardiovascular Diseases
• Official Title: Phenotypic and Epigenetic "Trained Immunity" Characteristics of Hematopoietic Stem and Progenitor Cells in Patients With Established Atherosclerosis
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: 4 Weeks

Biospecimen

Retention:   Samples With DNA

Description:

whole blood, serum, plasma and bone marrow

• 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.

Condition

• Atherosclerosis
• Cardiovascular Diseases

• Intervention: Not Provided

Study Groups/Cohorts

• Atherosclerosis group
  Patients with significant coronary artery disease.
• Control group
  Healthy controls without confirmed coronary artery disease.

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 29, 2019): 27
• Original Estimated Enrollment (submitted: May 29, 2017): 30
• Actual Study Completion Date: October 1, 2018
• Actual Primary Completion Date: August 31, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03172507
• Other Study ID Numbers: NL58806.091.16
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Radboud University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Radboud University Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Canisius-Wilhelmina Hospital

Investigators

• Principal Investigator: Niels P. Riksen, MD, PhD; Radboud University Medical Center

• PRS Account: Radboud University Medical Center
• Verification Date: October 2018