Effect of Statins on Trained Immunity

Atherosclerosis Clinical Trial

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: NCT02817230
• Other study ID #: 2014-1340
• Status: Completed
• Start date: June 2015
• Est. completion date: June 1, 2017

Study information

• Verified date: June 2023
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 1, 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Drug:
• Statin

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland
Netherlands	Erasmus Medical Center	Rotterdam

Sponsors (3)

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

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in histone methylation levels in circulating monocytes	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	Inflammatory phenotype		Baseline-3 months follow up