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

PROgression of FIbromuscular LEsions

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.

Study Overview

• Status: Completed
• Conditions: Fibromuscular Dysplasia
• Intervention / Treatment: Other: Abdominal and supra-aortic trunks vascular imaging; Genetic: Blood sampling (genetic); Other: Blood sampling (biomarkers); Other: Urine sampling

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 340
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels-Capital Region
    • Brussels, Brussels-Capital Region, Belgium, 1200
      • Cliniques universitaires Saint-Luc
• France
  • Alsace-Champagne-Ardenne-Lorraine
    • Vandeuvre-les-Nancy, Alsace-Champagne-Ardenne-Lorraine, France, 54500
      • CHU de Nancy institut Louis-Mathieu
  • Aquitaine-Limousin-Poitou-Charentes
    • Bordeaux, Aquitaine-Limousin-Poitou-Charentes, France, 33000
      • CHU de Bordeaux Hôpital Saint-André
  • Auvergne-Rhone-Alpes
    • Clermont-Ferrand, Auvergne-Rhone-Alpes, France, 63000
      • CHU de Clermont-Ferrand hopital Gabriel-Montpied
    • La Tronche, Auvergne-Rhone-Alpes, France, 38700
      • CHU de Grenoble hopital Albert-Michallon
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59000
      • CHRU de Lille Hôpital Cardiologique
    • Lille, Hauts-de-France, France, 59000
      • CHRU de Lille hopital Roger-Salengro
  • Ile-de-France
    • Le Chesnay, Ile-de-France, France, 78157
      • Centre Hospitalier de Versailles Hôpital Andre Mignot
    • Paris, Ile-de-France, France, 75010
      • Ap-Hp Hopital Lariboisiere
    • Paris, Ile-de-France, France, 75013
      • AP-HP Hopital Pitie-Salpetriere
    • Paris, Ile-de-France, France, 75014
      • Centre Hospitalier Sainte-Anne
    • Paris, Ile-de-France, France, 75015
      • Groupe Hospitalier Paris Saint-Joseph
    • Paris, Ile-de-France, France, 75018
      • AP-HP hopital Bichat-Claude-Bernard
    • Paris, Ile-de-France, France, 75020
      • AP-HP Hopital Tenon
  • Languedoc-Roussillon-Midi-Pyrenees
    • Toulouse, Languedoc-Roussillon-Midi-Pyrenees, France, 31000
      • CHU de Toulouse Hôpital Rangueil
  • Normandie
    • Caen, Normandie, France, 14000
      • CHU de Caen Hopital Cote de Nacre
  • Provence-Alpes-Cote d'Azur
    • Marseille, Provence-Alpes-Cote d'Azur, France, 13385
      • AP-HM Hôpital de La Timone

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Prospective cohort; 3 years follow-up

Other: Abdominal and supra-aortic trunks vascular imaging; 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.; Genetic: Blood sampling (genetic); 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.; Other: Blood sampling (biomarkers); 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.; Other: Urine sampling; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single nucleotide polymorphisms	Assessed by genome-wide association	Inclusion
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
Plasminogen/plasmin level		Inclusion
Matrix metalloproteinases level		Inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Fondation de Recherche sur l'Hypertension Artérielle
• Investigators: Principal Investigator: Pierre-François Plouin, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2009
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: November 7, 2016
• First Submitted That Met QC Criteria: November 10, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): September 23, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Renal Artery Obstruction; Carotid Artery Diseases; Genetic Association Studies
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Fibromuscular Dysplasia
• Other Study ID Numbers: P071241 (Other Identifier: Assistance Publique - Hopitaux de Paris); 2009-A00288-49 (Other Identifier: Agence Française de Securite Sanitaire des Produits de Sante); PHRC-08-192 (Other Grant/Funding Number: Direction Generale de l'Offre de Soin)