Clinical trial NCT01967511: Defining the Basis of Fibromuscular Dysplasia (FMD)
Official title: Defining the Basis of Fibromuscular Dysplasia: The Define-FMD Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Fibromuscular Dysplasia
Spontaneous Coronary Artery Dissection
Cervical Artery Dissection
Keywords: Cross-sectional study
Fibromuscular dysplasia
Fibroblast
Spontaneous Coronary Artery Dissection
Cervical Artery Dissection
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2013-10-23
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Will enroll 200 FMD patients, 100 SCAD patients, and 100 CvAD patients at the Mount Sinai Hospital. 200 matched healthy controls will also be recruited to this study.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Identification of regulatory gene networks
timeFrame: single time point at study enrollment
Secondary outcomes:
measure: Identification of molecular features
timeFrame: single time point at study enrollment
measure: Identification of genomic features
timeFrame: single time point at study enrollment
measure: RNA sequencing
timeFrame: single time point at study enrollment
measure: Circulating cytokine
timeFrame: single time point at study enrollment
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Jason Kovacic, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Jeffrey Olin, DO
role: PRINCIPAL_INVESTIGATOR
References:
citation: Olin JW, Di Narzo AF, d'Escamard V, Kadian-Dodov D, Cheng H, Georges A, King A, Thomas A, Barwari T, Michelis KC, Bouchareb R, Bander E, Anyanwu A, Stelzer P, Filsoufi F, Florman S, Civelek M, Debette S, Jeunemaitre X, Bjorkegren JLM, Mayr M, Bouatia-Naji N, Hao K, Kovacic JC. A plasma proteogenomic signature for fibromuscular dysplasia. Cardiovasc Res. 2020 Jan 1;116(1):63-77. doi: 10.1093/cvr/cvz219.
citation: Kiando SR, Tucker NR, Castro-Vega LJ, Katz A, D'Escamard V, Treard C, Fraher D, Albuisson J, Kadian-Dodov D, Ye Z, Austin E, Yang ML, Hunker K, Barlassina C, Cusi D, Galan P, Empana JP, Jouven X, Gimenez-Roqueplo AP, Bruneval P, Hyun Kim ES, Olin JW, Gornik HL, Azizi M, Plouin PF, Ellinor PT, Kullo IJ, Milan DJ, Ganesh SK, Boutouyrie P, Kovacic JC, Jeunemaitre X, Bouatia-Naji N. PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance. PLoS Genet. 2016 Oct 28;12(10):e1006367. doi: 10.1371/journal.pgen.1006367. eCollection 2016 Oct.
citation: Adlam D, Olson TM, Combaret N, Kovacic JC, Iismaa SE, Al-Hussaini A, O'Byrne MM, Bouajila S, Georges A, Mishra K, Braund PS, d'Escamard V, Huang S, Margaritis M, Nelson CP, de Andrade M, Kadian-Dodov D, Welch CA, Mazurkiewicz S, Jeunemaitre X; DISCO Consortium; Wong CMY, Giannoulatou E, Sweeting M, Muller D, Wood A, McGrath-Cadell L, Fatkin D, Dunwoodie SL, Harvey R, Holloway C, Empana JP, Jouven X; CARDIoGRAMPlusC4D Study Group; Olin JW, Gulati R, Tweet MS, Hayes SN, Samani NJ, Graham RM, Motreff P, Bouatia-Naji N. Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection. J Am Coll Cardiol. 2019 Jan 8;73(1):58-66. doi: 10.1016/j.jacc.2018.09.085.
citation: Georges A, Albuisson J, Berrandou T, Dupre D, Lorthioir A, D'Escamard V, Di Narzo AF, Kadian-Dodov D, Olin JW, Warchol-Celinska E, Prejbisz A, Januszewicz A, Bruneval P, Baranowska AA, Webb TR, Hamby SE, Samani NJ, Adlam D, Fendrikova-Mahlay N, Hazen S, Wang Y, Yang ML, Hunker K, Combaret N, Motreff P, Chedid A, Fiquet B, Plouin PF, Mousseaux E, Azarine A, Amar L, Azizi M, Gornik HL, Ganesh SK, Kovacic JC, Jeunemaitre X, Bouatia-Naji N. Rare loss-of-function mutations of PTGIR are enriched in fibromuscular dysplasia. Cardiovasc Res. 2021 Mar 21;117(4):1154-1165. doi: 10.1093/cvr/cvaa161.