Defining the Basis of Fibromuscular Dysplasia: The Define-FMD Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 600
- Locations
- 1
- Primary Endpoint
- Identification of regulatory gene networks
Study Overview
Brief Summary
The purpose of this study has evolved and expanded since its inception. Originally the intent was to establish the functional, molecular and genetic profile of fibroblasts from Fibromuscular Dysplasia (FMD) patients as compared to carefully matched control subjects. While this remains among the objectives, the study has been expanded to undertake a fully powered cross-tissue systems genetics analysis of FMD, and now also the related arteriopathies spontaneous coronary artery dissection (SCAD) and cervical artery dissection (CvAD). The overall objective is to disclose the core biologic mechanisms of these disorders.
Detailed Description
Specific aims
- Specific aim 1: To establish a library of fibroblasts, DNA, plasma and serum from patients with FMD, SCAD and CvAD and unaffected healthy control subjects.
- Specific aim 2: To perform a fully powered cross-tissue systems analysis of the key regulatory gene networks and disease drivers underlying FMD, SCAD and CvAD.
- Specific aim 3: To cross-compare the molecular and genomic profiles of FMD, SCAD and CvAD to establish the degree of biologic similarity among these disorders.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Patients of any age and freely willing to participate. For patients < 18 years of age consent will be via parents.
- •Fluency in either English or Spanish.
- •Signed, informed consent
- •For FMD, SCAD or CvAD subjects - a clinical diagnosis of FMD, SCAD or CvAD with fulfillment of standard diagnostic criteria.
- •For healthy controls - no clinical features of FMD, SCAD or CvAD and absence of any major ongoing systemic disease including any condition requiring hospitalization, immune suppression, intravenous or injected medications or that result in functional impairment in the performance of activities of daily living. Healthy controls will be matched to enrolled FMD patients on the basis of gender and approximate age (within a 5 year window of another FMD subject).
Exclusion Criteria
- •Patients who have co-morbidities which reduces life expectancy to one year.
- •Patients with any solid organ or hematological transplantation, or those in whom transplantation is considered.
- •Active autoimmune disease.
- •Illicit drug use.
- •HIV positive.
- •Prior malignancy.
- •Any other form of vascular disease, including other arteriopathy coronary artery disease or peripheral vascular disease
- •Family history of arteriopathy other than FMD, SCAD or CvAD (e.g. Ehlers-Danlos syndrome)
Arms & Interventions
FMD subjects
patients who fulfill standard diagnostic criteria for FMD
SCAD subjects
patients who fulfill standard diagnostic criteria for SCAD
CvAD subjects
patients who fulfill standard diagnostic criteria for CvAD
Healthy control subjects
Outcomes
Primary Outcomes
Identification of regulatory gene networks
Time Frame: single time point at study enrollment
The identification of regulatory gene networks, and their key drivers, underlying FMD, SCAD and CvAD
Secondary Outcomes
- RNA sequencing(single time point at study enrollment)
- Identification of molecular features(single time point at study enrollment)
- Identification of genomic features(single time point at study enrollment)
- Circulating cytokine(single time point at study enrollment)
Investigators
Jason Kovacic
Professor, Cardiology
Icahn School of Medicine at Mount Sinai