Epigenetic Analysis of Regulation of the Inflammasome-activating NLRP3 Gene in Monocytes From Atrial Fibrillation Patients and Controls

April 23, 2024 updated by: Tulane University
The study will analyze blood from volunteers to determine whether there is an underlying epigenetic cause of the inflammation of the heart associated with atrial fibrillation (AF) and its progression with age. Confirming the regions of epigenetic elements associated with upregulation of the inflammatory genes will help the investigators in identifying target sites for developing future therapeutic interventions. The investigators propose to confirm the monocyte-cell type specific DNA methylation profile of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and determine the age-related and AF-related changes in DNA methylation and expression of NLRP3 in monocytes. This study will provide insights into the epigenetic regulation of NLRP3 in young and elderly patients, as well as in AF patients vs. controls which will help in devising methods of modulating NLRP3 expression and decreasing cardiac fibrosis progression.

Study Overview

Status

Completed

Conditions

Detailed Description

Blood samples will be collected from 30 female participants as follows: 10 women between the ages of 50 - 80 years diagnosed with AF as evidenced by rhythm strips or written documentation; 10 healthy women subjects between the ages of 50-80 years and 10 healthy women between the ages of 20-30 years.

Participants will be recruited from the Tulane University Cardiology Clinics and also from volunteer research registries. These participants will be asked for consent to draw for another 8 ml (1.5 teaspoons) of blood during routine diagnostic blood draws. These blood samples will be de-identified by the PI upon receipt and no identifiable information will be maintained. Leukocyte subtypes including monocytes, neutrophils and B cells will be isolated from blood and DNA extraction will be carried out from the leukocyte subtypes. These leukocyte DNA samples will be sent to New England Biolabs, Ipswich, Massachusetts for DNA methylation analysis to identify target regions of epigenetic elements associated with upregulation of NLRP3 gene expression that might be related to disease progression with age. Real-Time Polymerase chain reaction (PCR) will be carried out at Tulane Research and Innovation for Arrhythmia Discoveries (TRIAD) Center, Tulane University School of Medicine from RNA extracted from leukocyte subtype to check the level of expression of NLRP3 highly associated with inflammation in AF.

Study Type

Observational

Enrollment (Actual)

29

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

  • United States
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Medical Center

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

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Participants will be recruited from the Tulane University Cardiology Clinics. The control healthy women subjects will be those scheduled for routine annual health check-up and healthy blood donors without any documentation of cardiovascular disease or other serious immune-related illnesses, such as diabetes, hypertension, autoimmune arthritis etc.

The patient population will include women subjects between the ages 50 to 80 years diagnosed with AF as evidenced by rhythm strips or written documentation.

Recruitment will also be done using volunteer research registries.

Description

Inclusion Criteria:

  • Subjects aged 18 or above,

  • Control Group scheduled for routine annual health check-up and healthy blood donors without any documentation of cardiovascular disease or other serious immune-related illnesses, such as diabetes, hypertension, autoimmune arthritis etc

    • healthy women subjects between the ages of 50-80 years
    • healthy women subjects between the ages of 20-30 years.

Study Patients -women between the ages of 50 - 80 years diagnosed with AF as evidenced by rhythm strips or written documentation.

Exclusion Criteria:

  • Previous left atrial ablation or any type of valvular surgery
  • Patients who are taking medications like Ibuprofen, Toradol, Naproxen and other common over-the -counter NSAIDs.
  • Women who are pregnant
  • Terminally ill patients

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
Patient Group
10 women between the ages of 50 - 80 years diagnosed with AF as evidenced by rhythm strips or written documentation.
Control Group 1
10 healthy women subjects between the ages of 50-80 year
Control Group 2
10 healthy women subjects between the ages of 20-30 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine whether there is an underlying epigenetic cause of the inflammation of the heart associated with atrial fibrillation
Time Frame: Day 1
This will be determined by confirming the monocyte-cell type specific DNA methylation profile of NLRP3.
Day 1
Determine whether there are significant associations of DNA methylation with NLRP3 expression in monocytes with advancing age.
Time Frame: Day 1
Age association will be examined by comparing group wise the DNA methylation levels of monocytes from young vs. old individuals. The level of NLRP3 expression will be compared to the levels of DNA methylation.
Day 1
Determine whether there are significant associations of DNA methylation with NLRP3 expression in monocytes with the status of atrial fibrillation.
Time Frame: Day 1
Disease associations will be tested by comparing group wise the DNA methylation levels of monocytes from AF patients vs. controls. The investigators will also test for understanding significant association of NLRP3 expression with corresponding DNA methylation status in AF patients.
Day 1

Collaborators and Investigators

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

Sponsor

Tulane University

Collaborators

Louisiana Clinical and Translational Science (LA CaTS) Center Clinical Research Resources Core

Investigators

  • Principal Investigator: Sruti Chandra, PhD, Tulane University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

October 22, 2021

Primary Completion (Actual)

February 16, 2024

Study Completion (Actual)

February 16, 2024

Study Registration Dates

First Submitted

February 8, 2021

First Submitted That Met QC Criteria

February 19, 2021

First Posted (Actual)

February 23, 2021

Study Record Updates

Last Update Posted (Actual)

April 25, 2024

Last Update Submitted That Met QC Criteria

April 23, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-561

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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