Cohort Follow-up of Patients With Renal or Craniocervical Fibromuscular Dysplasia

Study Overview
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Brief Summary
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PROFILE is a cohort study evaluating the progression of fibromuscular dysplasia lesions. This study is the prospective dimension of ARCADIA registry (ClinicalTrials.gov Identifier: NCT02884141), which aims to document phenotypic and genetic traits in patients with renal and/or cervical artery fibromuscular dysplasia.

Detailed Description
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Background Fibromuscular dysplasia (FMD) is a group of nonatherosclerotic, noninflammatory arterial diseases that usually involve renal and carotid arteries. Patients with FMD may present with renovascular hypertension and/or with cerebrovascular symptoms. The prevalence of FMD in hypertensive patients is estimated at 4/1000. Angiographic classification includes the multifocal type, with multiple stenoses and the 'string-of-beads' appearance that is related to medial FMD, and tubular and focal types which are not clearly related to specific histological lesions. FMD may affect one or more vascular beds and progress to more severe stenosis and to renal or cerebrovascular complications. FMD appears to be familial in 10% of cases (OMIM #135580). Renal artery FMD may progress to more severe stenosis and to renal atrophy, and/or to stenoses affecting more arteries within or outside the renal vasculature. The risk of progression as assessed from available studies was probably overestimated because documentation of progression was obtained from angiography, a procedure which is not routinely undertaken in patients with favourable clinical and biological outcomes. The disease is progressive, however, and literature stated that patients with FMD should undergo yearly duplex ultrasonography to detect progression of disease, restenosis, or loss of kidney volume. There are very few data on prognosis of patients with symptomatic carotid or vertebral artery FMD. The risk of arterial disease progression over time is unknown. The risk of ischemic stroke ranged from 0 to about 3% per year in the few studies which assessed that issue. Objectives The primary objective is to estimate the incidence and risk factors for progression of FMD lesions. This will be assessed by comparison between initial and 3 years abdominal and supra-aortic trunks vascular imaging (angiography, CT-angiography or Magnetic Resonance (MR) angiography), monitoring of downstream consequences development of lesions progression and clinical events. The secondary objectives are: to estimate rate of genetic polymorphism that may influence disease progression or be associated with complications to assess the frequency of multi-site FMD (common objective with the ARCADIA study) to collect standardized clinical, radiological, and biological data in patients with FMD through a national registry (common objective with the ARCADIA study) to organize a clinical, radiological and biological database and a biobank that will constitute a unique resource to initiate further clinical research (common objective with the ARCADIA study).

Official Title
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PROgression of FIbromuscular LEsions

Conditions
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Fibromuscular Dysplasia

Intervention / Treatment
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* Other: Abdominal and supra-aortic trunks vascular imaging
* Genetic: Blood sampling (genetic)
* Other: Blood sampling (biomarkers)
* Other: Urine sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with renal or craniocervical fibromuscular dysplasia diagnosed during the 2 years before inclusion The fibromuscular dysplasia is documented by imaging (angiography, CT-angiography, MR-angiography) of less than 2 years and validated by a radiologist investigator Patient who understood and signed inform consent form Affiliated to the French health insurance system Available for a 3 years follow-up Exclusion Criteria: Patient with renal or craniocervical atherosclerosis, or inflammatory vascular disease as dominant pathological features Patient with renal or craniocervical arteries dissection or aneurysm without any other evidence of fibromuscular dysplasia Patient under 18 or under tutorship Known pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prospective cohort<br>3 years follow-up | Other: Abdominal and supra-aortic trunks vascular imaging<br>* Abdominal and supra-aortic trunks vascular imaging (angiography, CT-angiography or MR-angiography) will be performed 3 years after inclusion. This imaging will be compare to initial imaging (which is a part of usual care, not an intervention added by the study) in order to assess FMD progression.<br>Genetic: Blood sampling (genetic)<br>* A sample of blood will be taken to meet the objective of estimating the rate of genetic polymorphism that may influence disease progression or be associated with complications.<br>Other: Blood sampling (biomarkers)<br>* A sample of blood will be taken to biomarkers analysis to meet the primary objective of assessing the risk factors for progression of FMD lesions.<br>Other: Urine sampling<br>* A sample of urine will be taken to biomarkers analysis to meet the primary objective of assessing the risk factors for progression of FMD lesions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of fibromuscular dysplasia lesions confirmed by imaging |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular filtration rate (GFR) |  | Inclusion, 3 years | 
| Kidney height |  | Inclusion, 3 years | 
| Clinical event: revascularization procedure in a lesion site |  | Through study completion | 
| Clinical event: renal infarction |  | Through study completion | 
| Clinical event: ischemic stroke |  | Through study completion | 
| Clinical event: arterial dissection in a lesion site or downstream from a lesion site |  | Through study completion | 
| Clinical event: aneurysm rupture in a lesion site or downstream from a lesion site |  | Through study completion | 
| Prevalence of multisite fibromuscular dysplasia confirmed by imaging |  | Inclusion, 3 years | 
| Single nucleotide polymorphisms | Assessed by genome-wide association | Inclusion | 
| Plasminogen/plasmin level |  | Inclusion | 
| Matrix metalloproteinases level |  | Inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Artery Obstruction, Carotid Artery Diseases, Genetic Association Studies