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

NCT04766814 | Completed

• 1 other identifier: 2020-561
• Study Type: observational
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atrial Fibrillation; Arrhythmia

Keywords

Inflammation; Stroke; DNA methylation

Outcome Measures

Primary Outcomes (3)

• Determine whether there is an underlying epigenetic cause of the inflammation of the heart associated with atrial fibrillation

  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.

  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.

  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

Study Arms (3)

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

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Tulane University: lead
• Louisiana Clinical and Translational Science (LA CaTS) Center Clinical Research Resources Core: collaborator

Study Sites (1)

Tulane University Medical Center

New Orleans, Louisiana, 70112, United States

Location

Related Publications (25)

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MeSH Terms

Conditions

Atrial Fibrillation; Arrhythmias, Cardiac; Inflammation; Stroke

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Study Officials

• Sruti Chandra, PhD

  Tulane University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 23, 2021
• Study Start: October 22, 2021
• Primary Completion: February 16, 2024
• Study Completion: February 16, 2024
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

US (1)