The Effect of Statin Treatment on Trained Innate Immunity

Completed

• Conditions: Atherosclerosis
• Interventions: Drug: statin treatment

• Registration Number: NCT03354156
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2016-04-21
• Status Verified: 2016-10
• Primary Completion: 2016-11
• Study Completion: 2016-12
• Study First Submitted QC: 2017-11-23
• Last Update Submitted: 2017-11-23
• Study First Posted: 2017-11-27
• Last Update Posted: 2017-11-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

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

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Exclusion Criteria

• previous cardiovascular events.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
High-LDL	statin treatment	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.

Primary Outcome Measures

Name	Time	Method
Cytokine production capacity	baseline	Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Radboud university medical center; 🇳🇱 Nijmegen, Netherlands