CAUSE Trial: Patient Specific-Cellular Characterization of Fibromuscular Dysplasia and High-Risk Atherosclerotic Endothelium

NCT01808729 | Completed

• 2 other identifiers: GCO 11-1601HS#: 11-02041
• Study Type: observational
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this project is to see if heritable alterations in the function, biology and vascular repair capacity of vascular cells make a major contribution to the burden of coronary artery disease (CAD), fibromuscular dysplasia (FMD), and other vascular diseases. In more detail, FMD is a nonatherosclerotic vascular disease that primarily affects women aged 20 to 60. It commonly affects the renal and carotid arteries but may involve almost every artery in the body. At the cellular level, FMD is characterized by increased fibroblast proliferation and collagen deposition. This study aims to define some of these cellular problems by directly studying fibroblast cells from FMD patients and healthy control subjects. Similarly, CAD is among the leading causes of death worldwide. However, a large part of the risk for CAD is unexplained. It is thought that a major but undefined risk factor may be gene (genomic) variations causing a change in vascular cell function. Here, we will study important vascular cell types in patients with severe and early onset CAD in an attempt to define these problems. Therefore, in summary, this study will look to define the various cellular-level problems that occur in patients with both in CAD and FMD. These data will be linked to DNA-level analyses to ultimately attempt to define the cause of these conditions.

Conditions

Fibromuscular Dysplasia; Early Onset CAD

Keywords

fibromuscular dysplasia; coronary artery disease

Outcome Measures

Primary Outcomes (1)

• Phenotypic cellular differences (fibroblasts and/or ps-iPSC-ECs) between cases and controls

  We aim to define the underlying basis of FMD, early onset CAD and other rare vascular diseases using a combination of cellular phenotyping, DNA and plasma analysis comparing data between cases and controls at baseline with data collected from hospital chart review.

  baseline

Study Arms (2)

FMD or CAD (as appropriate)

The study group will either have FMD, early onset CAD, or other rare/unusual vascular disorder. These differing disorders will be sub-groups within the overall study

Healthy control subjects without vascular disease

Healthy controls will not exhibit signs, symptoms or other evidence of vascular disease.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Eligible subjects will be recruited from the clinical care areas of Mount Sinai Hospital, including outpatient clinics and the catheterization laboratory. Subjects will either have a confirmed diagnosis of FMD, early onset CAD, or other rare vascular disease as outlined above. Healthy controls will also be selected as age- and gender- matched persons without these disorders, ideally healthy related siblings if available.

You may qualify if:

• Clinical diagnosis of FMD based on current guideline criteria and relevant imaging results.
• For ET-CAD (early onset CAD) = patients \<50 years of age for males and \<55 for females with \>60% stenosis in ≥2 coronary arteries or their branches, or SYNTAX score ≥12 (significant CAD), in the absence of acquired CAD risk factors.
• Patients with \>60% stenosis in ≥2 coronary arteries or their branches, or SYNTAX score ≥12, will also be eligible for the ET-CAD group as follows: a) \<40 years of age for males and \<45 for females in the presence of one acquired risk factor; b) \<35 years of age for males or females and two acquired risk factors.
• Patients already having undergone revascularization will be eligible if other criteria are fulfilled and an aggregate SYNTAX score of ≥12 would have been reached for all treated lesions, or there was disease in ≥2 coronary arteries or their branches, according to the criteria (1) and (2) above.
• For Healthy Controls = age matched patients who have undergone angiography and who do not have CAD ('normal coronary arteries'; SYNTAX score = 0) but with ≥2 acquired CAD risk factors. Control subjects for the FMD studies will be unaffected family members, or unrelated persons matched for age and gender.
• a. Age \>18 years;
• b. Fluency in English or Spanish (Spanish consent forms will be provided);
• c. Freely willing to participate with signed informed consent.
• Acquired Risk Factors are defined as:
• (1) Diabetes for \>2 years or HBA1C \>10.0%;
• (2) Smoker of \>5 pack-years for entire lifetime;
• (3) Obesity (BMI \>30kg/m2);
• (4) Dyslipidemia, defined by use of lipid lowering therapy, physician diagnosis of dyslipidemia, serum total cholesterol \>240 mg/dL or low-density lipoprotein-cholesterol \>100 mg/dL;
• (5) Hypertension according to guidelines or requiring therapy.

You may not qualify if:

• Smoking \>2 packets of cigarettes/day for \>12 months;
• Prior total cholesterol level of \>400mg/dl;
• BMI \>40 kg/m2;
• Uncontrolled or severe diabetes with prior hospitalization due to diabetic complications other than at diagnosis;
• For ET-CAD patients: Uncontrolled or severe hypertension causing hospitalization or direct complications;
• Serum creatinine ≥2.0 mg/dL;
• Heart transplantation;
• Active autoimmune disease;
• Illicit drug use;
• HIV positive;
• Prior malignancy with mediastinal irradiation, bone marrow transplantation or high-dose chemotherapy;
• Adult congenital heart disease;
• For healthy controls only, a positive family history of CAD or FMD.
• Also, as an extension of this study, patients presenting with rare, undiagnosed or unusual forms of CAD (e.g. unexplained dissection, fulminant calcification, aneurysms etc.) and FMD and appropriate controls, will be recruited, particularly if there is a strong family pedigree.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA from leukocytes, plasma, fibroblasts and fibroblast-derived cell lines

MeSH Terms

Conditions

Fibromuscular Dysplasia; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis

Study Officials

• Jason Kovacic, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2013
• First Posted: March 11, 2013
• Study Start: February 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 5, 2013

Record last verified: 2013-11

Locations

US (1)