Effect of Statins on Trained Immunity

November 28, 2023 updated by: Radboud University Medical Center

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

In this study, the investigators will determine whether patients with elevated levels of LDL are characterized by specific epigenetic changes in circulating cells of the innate immune system, compared to control subjects with healthy levels of LDL and whether regular statin treatment influences these changes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Rationale: 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. Here the investigators hypothesize that monocytes of patients with elevated LDL cholesterol levels show epigenetic changes compared to normocholesterolemic subjects and that this can be reversed by treatment with statins.

Objective: The main objective is to study whether patients with elevated levels of LDL show increased Histone 3 Lysine 4 trimethylation in the promoter regions of pro-inflammatory cytokines and have an augmented ex vivo Toll-Like Receptor agonist-induced cytokine production in isolated monocytes compared to controls. Subsequently the investigators will study the effect of treatment with statins on these responses.

Study design: Observational study Study population: Subjects aged >18 years who have been referred to the out-patient clinic and have LDL levels that require lipid lowering treatment and matched normocholesterolemic control subjects.

Study Type

Observational

Enrollment (Actual)

45

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Academic Medical Center
      • Rotterdam, Netherlands
        • Erasmus Medical Center
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500HB
        • Radboud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Subjects aged >18 years who have been referred to the out-patient clinic and have LDL levels that require lipid lowering treatment (LDL>4.9 mmol/l)

Description

Inclusion Criteria:

Patients:

  • 18 years or older
  • Elevated LDL levels (>4.9 mmol/l)
  • No previous cardiovascular events

Controls:

  • Age > 18 years
  • LDL cholesterol < 3.5 mmol/l
  • No previous cardiovascular events

Exclusion Criteria:

  • Current lipid lowering treatment
  • Known malignant disorders, auto-immune disorder, or diabetes
  • Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study
  • Clinical signs of acute infection
  • Use of anti-inflammatory medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients
Patients referred to the out-patient clinic with LDL levels >4.9 mmol/l
Drug: Statin
Controls
Matched normocholesterolemic control subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in histone methylation levels in circulating monocytes
Time Frame: Baseline-3 months follow up
Histone methylation levels on different lysines of histone 3 will be analyzed at baseline and after 3 months of statin treatment
Baseline-3 months follow up

Secondary Outcome Measures

Outcome Measure
Time Frame
Inflammatory phenotype
Time Frame: Baseline-3 months follow up
Baseline-3 months follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

Erasmus Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

June 1, 2017

Study Registration Dates

First Submitted

June 15, 2016

First Submitted That Met QC Criteria

June 24, 2016

First Posted (Estimated)

June 29, 2016

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014-1340

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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