DNA Methylation in PMR
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 50
- Primary Endpoint
- Understanding what the exact triggers for immune activation, the specific antigens involved, and the mechanisms underlying disease relapses and glucocorticoid resistance
Study Overview
Brief Summary
Polymyalgia Rheumatica (PMR) is treated with corticosteroids; however, long-term treatment is not feasible due to side effects. Withdrawal of corticosteroids causes a subset of patients to relapse, and there is no current way to understand what underlies this. Our research team has preliminary data from a small clinical study that indicates that different immune effector dynamics during the tapering of steroids correlate with relapse. This was achieved using the DNA methylation-specific immune cell profiling methods that Dr. Christensen has pioneered. What is proposed is a larger prospective study of 50 PMR patients to validate differences in CD4 and CD8 memory cells as a predictor of relapse. Finally, we also focus on the Glucocorticoid Methylation Index (GCMI), which is a collection of 28 CpG islands that are methylated in response to corticosteroids. This will allow our team to determine the predictive power of the GCMI for PMR.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 50 Years to 89 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Anyone ≥50-89 years old Taking ≥10mg of prednisone or prednisone equivalent at time of enrollment with a stable disease normal ESR and CRP (inflammation markers) which would indicate presence of inflammation or not
- •CRP: <1.0 mg/dL (some labs report in mg/L → normal is usually <3 mg/L)
- •Men ≥50 years: 0-20 mm/hr
- •Women ≥50 years: 0-30 mm/hr Have a PMR diagnosis Able to provide written consent
Exclusion Criteria
- •History of concomitant Giant cell arteritis (GCA) any other rheumatological disorders like lupus, arthritis (psoriatic, osteo), scleroderma, sjogrens Active malignancy- presence of tumor by imaging or labs Infection- infection can cause increased levels of innate immune cells making it difficult to differentiate between disease and infection recent surgery- within the past 6 months
Arms & Interventions
PMR diagnosed
individuals who have a PMR diagnosis
Healthy Volunteers
Healthy individuals, without a PMR diagnosis, which will allow age and sex matches with the PMR diagnosed cohort.
Outcomes
Primary Outcomes
Understanding what the exact triggers for immune activation, the specific antigens involved, and the mechanisms underlying disease relapses and glucocorticoid resistance
Time Frame: 12 months
DNA methylation cytometry is a novel DNA-based cell typing technology that can quantify changes in blood immune cells. The methylation cytometry approach allows for an in-depth insight into 12 immune cell populations (and over 50 immune profile variables) that is not feasible with standard clinical labs. It is both far more affordable and less labor-intensive than flow cytometry, as well as much less logistically complex because it is DNA-based and does not require intact cell membranes.14 Blood can be collected as part of the standard-of-care draw and immediately frozen for later use. DNA methylation analysis is a novel approach to understanding the immunologic underpinnings of PMR pathogenesis and treatment.
Secondary Outcomes
No secondary outcomes reported
Investigators
Vivekanand.Tiwari
Assistant Professor of Medicine, Staff Rheumatologist
Dartmouth-Hitchcock Medical Center