Effect of Statins on Trained Immunity

Sponsor

Radboud University Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT02817230

Collaborator

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

Enrollment

Locations

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: Statin

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 Design

Study Type:

Observational

Anticipated Enrollment :

45 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Jun 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Jun 1, 2017

Arms and Interventions

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

Arm

Intervention/Treatment

Patients

Patients referred to the out-patient clinic with LDL levels >4.9 mmol/l

Drug: Statin

Controls

Matched normocholesterolemic control subjects

Outcome Measures

Primary Outcome Measures

Changes in histone methylation levels in circulating monocytes [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

Secondary Outcome Measures

Inflammatory phenotype [Baseline-3 months follow up]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland	Netherlands	6500HB
2	Academic Medical Center	Amsterdam		Netherlands
3	Erasmus Medical Center	Rotterdam		Netherlands

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Radboud University Medical Center

ClinicalTrials.gov Identifier:

NCT02817230

Other Study ID Numbers:

2014-1340

First Posted:

Jun 29, 2016

Last Update Posted:

Jun 29, 2016

Last Verified:

Jun 1, 2016

Additional relevant MeSH terms:

Atherosclerosis

Study Results

No Results Posted as of Jun 29, 2016