Defining the Basis of Fibromuscular Dysplasia (FMD)

Spontaneous Coronary Artery Dissection Clinical Trial

— DEFINE  

Official title:

Defining the Basis of Fibromuscular Dysplasia: The Define-FMD Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01967511
• Other study ID #: GCO 13-1118
• Status: Recruiting
• Start date: October 2013
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Jason Kovacic, MD, PhD
• Phone: 212-241-7014
• Email: jason.kovacic[@]mountsinai.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Aortic Dissection
• Cervical Artery Dissection
• Coronary Vessel Anomalies
• Fibromuscular Dysplasia
• Hyperplasia
• Spontaneous Coronary Artery Dissection
• Vascular Diseases

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

References & Publications (4)

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 Conso — View 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, W — View 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, Gorn — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of regulatory gene networks	The identification of regulatory gene networks, and their key drivers, underlying FMD, SCAD and CvAD	single time point at study enrollment
Secondary	Identification of molecular features	To cross-compare the molecular features of FMD, SCAD and CvAD	single time point at study enrollment
Secondary	Identification of genomic features	To cross-compare the genomic features of FMD, SCAD and CvAD	single time point at study enrollment
Secondary	RNA sequencing	To define and compare the genomic (RNA sequencing) profile of fibroblasts from FMD, SCAD and CvAD subjects versus healthy control subjects	single time point at study enrollment
Secondary	Circulating cytokine	To define and compare the circulating cytokine profile of FMD versus healthy control subjects.	single time point at study enrollment