The Effect of Statin Treatment on Trained Innate Immunity (SIMPEL)

Effect of Statins on Epigenetic Reprogramming of Monocytes in Patients With Elevated Levels of LDL

The innate immune system plays a pivotal role in the development and progression of atherosclerosis. Recently, it was reported that monocytes can develop a long-lasting immunological memory after stimulation with various microorganisms, which has been termed 'trained innate immunity'. This memory is induced by epigenetic reprogramming, in particular trimethylation of lysine 4 at histone 3 (H3K4me3).

In this study, the investigators aim to investigate the immunophenotype of circulating monocytes in patients with elevated LDL cholesterol levels and the effect of statins on this phenotype.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: statin treatment

Detailed Description

The innate immune system plays a pivotal role in the development and progression of atherosclerosis. Recently, it was reported that monocytes can develop a long-lasting immunological memory after stimulation with various microorganisms, which has been termed 'trained innate immunity'. This memory is induced by epigenetic reprogramming, in particular trimethylation of lysine 4 at histone 3 (H3K4me3).

The main objective is to study whether circulating monocytes of patients with elevated levels of LDL have a phenotype of trained innate immunity compared to control patients. Subsequently the investigators will study the effect of treatment with statins on the increased inflammatory response and epigenetic changes of the innate immune system.

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500 GA
    • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the outpatient clinics of the Radboudumc, AMC, or Erasmus MC, with LDL cholesterol levels >4.9 mmol/l, who will treated with statins according to current guidelines, will be will be selected.

Description

Inclusion Criteria:

• Aged 18 years or older
• Elevated LDL levels (>4.9 mmol/l)
• Decision made by treating physician to initiate statin treatment

Exclusion Criteria:

• previous cardiovascular events.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High-LDL; patients with LDL cholesterol levels of >4.9 mmo/l, who have not been treated with statins in the past years, and who have an indication for treatment with statins.	Drug: statin treatment; The patients with elevated LDL receive statin treatment in the context of normal patient care (so this is NOT an intervention of the study)
Control; control subjects with an LDL cholesterol level of <3.5 mmol/l

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine production capacity	Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine production capacity	Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels	Three months after start of statin treatment
Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes.	Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes.	baseline
Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes.	Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes.	Three months after start of statin treatment

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Erasmus Medical Center; AIDS Malignancy Consortium

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: April 21, 2016
• First Submitted That Met QC Criteria: November 23, 2017
• First Posted (Actual): November 27, 2017

Study Record Updates

• Last Update Posted (Actual): November 27, 2017
• Last Update Submitted That Met QC Criteria: November 23, 2017
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis
• Other Study ID Numbers: NL50608.091.14

Plan for Individual participant data (IPD)

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