The Effect of Statin Treatment on Trained Innate Immunity

Atherosclerosis Clinical Trial

— SIMPEL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03354156
• Other study ID #: NL50608.091.14
• Status: Completed
• Phase: N/A
• First received: April 21, 2016
• Last updated: November 23, 2017
• Start date: January 2015
• Est. completion date: December 2016

Study information

• Verified date: October 2016
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

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)

Locations

Country	Name	City	State
Netherlands	Radboud university medical center	Nijmegen

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University	AIDS Malignancy Consortium, Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cytokine production capacity	Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels	baseline
Secondary	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
Secondary	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
Secondary	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