Fibromuscular DysplasiaNCT01808729
CAUSE Trial: Patient Specific-Cellular Characterization of Fibromuscular Dysplasia and High-Risk Atherosclerotic Endothelium
An observational study of Fibromuscular Dysplasia and Early Onset CAD, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Fibromuscular Dysplasia, Early Onset CAD
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Oct 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
- For all subjects, other inclusion criteria are:
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: The CAUSE Trial: Genomics of Extreme Trait-Coronary Artery Disease Cells and Fibromuscular Dysplasia Using Induced Pluripotent Stem Cell-Derived Endothelial Cells
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.
Read the detailed description
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.
Patients will be referred for this study by their physician if he/she feels that the patient qualifies for entry into the study based upon the Inclusion/Exclusion Criteria and is expected by their physician to be a suitable candidate. This will include: 1) patients with FMD and non-affected control subjects, 2) patients with early onset CAD in the absence of significant CAD risk factors, or matching healthy controls those with ≥2 cardiovascular risk factors and no CAD (those with angiographically 'normal' coronary arteries). Also, as an extension of this study, patients with rare, undiagnosed or unusual forms of CAD (e.g. unexplained dissection, fulminant calcification, aneurysms etc.) and appropriate controls, will be recruited, particularly if there is a strong family pedigree.
This study will include collection of whole blood for subsequent DNA isolation and sequencing, a plasma sample, and a skin biopsy. Blood will be handled in a standard fashion to obtain DNA from leukocytes and plasma. These will be stored pending later batched analysis. Once the skin biopsy tissue is collected, the tissue will be sent to the lab for further processing. The initial step is that we will derive fibroblasts from the skin biopsies. In brief, the biopsies are washed, cut into small fragments are distributed on a culture dish with growth medium and incubated at 37°C. Over the next 4 - 6 weeks, fibroblasts progressively grow and can be collected. We may then induce these fibroblasts to undergo changes so that they become stem cells (called "induced pluripotent stem cells" or iPSCs). Once we have made iPSCs, we can then make endothelial cells (iPSC-ECs), or in fact, many other cell types. The cells can be frozen until analysis, or until experiments are done in the future. All of the derived cells (fibroblasts, iPSCs and iPSC-ECs) generated under this protocol will be kept indefinitely, and may be used for future studies into the causes and other aspects of FMD or CAD.
This study is not concerned with any clinical events after patient enrollment. Only clinical events that have occurred prior to enrollment (e.g. prior myocardial infarction, stroke, dissection) will be recorded. Once we have obtained these cells, detailed cellular and molecular analyses will be performed to study the particular cellular defects that are associated with these differing conditions. This data will be combined with the DNA- and plasma-derived data in an attempt to define the underlying basis for these disorders.
As this is not a treatment, no alternative treatment options apply. The subject can decide not to participate in the trial. No benefit can be promised to any subject in this study. The information gained may benefit others with the same condition.
- Conditions
- Fibromuscular Dysplasia, Early Onset CAD
- Keywords
- fibromuscular dysplasia, coronary artery disease
- Medical subject headings
- Fibromuscular Dysplasia, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2013 (estimated)
- Study startFeb 2013
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fibromuscular DysplasiaStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jason Kovacic, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01808729
- Sponsor's protocol ID
- GCO 11-1601
- Other IDs
- HS#: 11-02041
- Status last verified
- Nov 2013
- First submitted
- 7 Mar 2013
- Last updated
- 5 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The CAUSE Trial: Genomics of Extreme Trait-Coronary Artery Disease Cells and Fibromuscular Dysplasia Using Induced Pluripotent Stem Cell-Derived Endothelial Cells
- ClinicalTrials.gov ID
- NCT01808729
- Acronym / sponsor ID
- GCO 11-1601
- Conditions
- Fibromuscular Dysplasia, Early Onset CAD
- Keywords
- fibromuscular dysplasia, coronary artery disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 11 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Patients will be referred for this study by their physician if he/she feels that the patient qualifies for entry into the study based upon the Inclusion/Exclusion Criteria and is expected by their physician to be a suitable candidate. This will include: 1) patients with FMD and non-affected control subjects, 2) patients with early onset CAD in the absence of significant CAD risk factors, or matching healthy controls those with ≥2 cardiovascular risk factors and no CAD (those with angiographically 'normal' coronary arteries). Also, as an extension of this study, patients with rare, undiagnosed or unusual forms of CAD (e.g. unexplained dissection, fulminant calcification, aneurysms etc.) and appropriate controls, will be recruited, particularly if there is a strong family pedigree.
This study will include collection of whole blood for subsequent DNA isolation and sequencing, a plasma sample, and a skin biopsy. Blood will be handled in a standard fashion to obtain DNA from leukocytes and plasma. These will be stored pending later batched analysis. Once the skin biopsy tissue is collected, the tissue will be sent to the lab for further processing. The initial step is that we will derive fibroblasts from the skin biopsies. In brief, the biopsies are washed, cut into small fragments are distributed on a culture dish with growth medium and incubated at 37°C. Over the next 4 - 6 weeks, fibroblasts progressively grow and can be collected. We may then induce these fibroblasts to undergo changes so that they become stem cells (called "induced pluripotent stem cells" or iPSCs). Once we have made iPSCs, we can then make endothelial cells (iPSC-ECs), or in fact, many other cell types. The cells can be frozen until analysis, or until experiments are done in the future. All of the derived cells (fibroblasts, iPSCs and iPSC-ECs) generated under this protocol will be kept indefinitely, and may be used for future studies into the causes and other aspects of FMD or CAD.
This study is not concerned with any clinical events after patient enrollment. Only clinical events that have occurred prior to enrollment (e.g. prior myocardial infarction, stroke, dissection) will be recorded. Once we have obtained these cells, detailed cellular and molecular analyses will be performed to study the particular cellular defects that are associated with these differing conditions. This data will be combined with the DNA- and plasma-derived data in an attempt to define the underlying basis for these disorders.
As this is not a treatment, no alternative treatment options apply. The subject can decide not to participate in the trial. No benefit can be promised to any subject in this study. The information gained may benefit others with the same condition.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Phenotypic cellular differences (fibroblasts and/or ps-iPSC-ECs) between cases and controls
Time frame: baseline
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Kovacic, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fibromuscular Dysplasia and Early Onset CAD, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phenotypic cellular differences (fibroblasts and/or ps-iPSC-ECs) between cases and controls (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2013.