Clinical trial NCT02817230: Effect of Statins on Trained Immunity
Official title: Effect of Statins on Epigenetic Reprogramming of Monocytes in Patients With Elevated Levels of LDL
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atherosclerosis
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Erasmus Medical Center
First posted: 2016-06-29
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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)

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in histone methylation levels in circulating monocytes
timeFrame: Baseline-3 months follow up
Secondary outcomes:
measure: Inflammatory phenotype
timeFrame: Baseline-3 months follow up
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
References: