Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02807714 |
| Other study ID # |
2042 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 2016 |
| Est. completion date |
December 2020 |
Study information
| Verified date |
February 2021 |
| Source |
Bassett Healthcare |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this study is to find an association between a protein named Podocan and WNT
pathway regulatory molecules in patients with different forms of Coronary Artery Disease
(Acute Coronary syndrome, Stable Angina and Coronary Artery Restenosis). It has been found in
experimental studies that this protein is regulating smooth muscle cell function and hence
may be influencing the progression of Coronary Artery Disease (CAD). We are testing to see if
the same regulatory function exists in human subjects. Studying patient's blood will possibly
enable to identify an association between Podocan and CAD. This may help to better prevent
and treat CAD with improved understanding of the mechanism of the disease. No drugs or other
therapeutic interventions will be used for the purpose of the research study. Only blood
samples will be collected in the cardiac catheterization lab. As a part of this study
participants will be followed for repeat events or repeat cardiac catheterization over a
period of 24 months.
Description:
Smooth muscle cells (SMC's) critically influence the clinical course of vascular disease .
The close regulation of SMC migration and proliferation within the intimal space is critical
in maintaining a delicate balance between insufficient and excessive atherosclerotic plaque
repair . When SMC proliferation is too suppressed, the ensuing weakening of the fibrous cap
can result in plaque vulnerability underlying Acute Coronary Syndrome and when SMC
proliferation is excessive, intimal hyperplasia as hallmark of accelerated Coronary Artery
Disease can follow such as in Restenosis post PCI. While stents have vastly improved upon the
recoil and constrictive remodeling component of restenosis, the problem of accelerated
intimal SMC growth has remained. The current approach of delivering stents releasing
non-specific agents promoting cell death and/or inhibition of proliferation has been
successful at lowering the need for recurrent vascular interventions . However, this success
comes at the expense of delaying vascular healing, whose ultimate long-term clinical impact
is still being evaluated. Short and long-term negative effects on the healing arterial wall
such as delayed re-endothelialization, increased inflammation and enhanced thrombogenicity of
drug-eluting stent (DES) are undisputed. These side effects of DES are being masked by
prolonged and aggressive dual anti-platelet therapy, which is exposing patients - especially
the elderly - to increased bleeding risks and complicates clinical decision-making. This
problem also causes fear of too early treatment cessation, demands rigorous patient
compliance and is costly. These issues are not trivial in daily clinical practice and the
lack of reliable clinical predictors of restenosis precludes individualized and patient
tailored stent selection.
Podocan is a protein within the Single Leucine Rich (SLR) protein family and is a previously
unrecognized component of the sclerotic glomerular lesion that develops in the course of
experimental HIV associated nephropathy . Its important role in regulating smooth muscle cell
function via the Wnt-pathway has been recently described by the investigators of this study .
It has been shown to modulate experimental arterial repair and a significantly different
expression pattern has been found in coronary arterial lesions obtained by directional
coronary atherectomy (DCA) from patients with restenosis compared to stable angina . These
findings do suggest a possible clinical predictive role of Podocan, and the Wnt-pathway
effectory molecules on the incidence of Instent Re-stenosis (ISR) and the need for Repeat
Target Vessel Revascularization.
All patients who present to the cardiac cath lab for angiography for the evaluation of known
or suspected CAD will be eligible for enrollment. It is expected that, based on angiographic
results, participants will fall into one of four categories:
1. No CAD
2. Stable CAD, no intervention required
3. Obstructive CAD requiring intervention (angioplasty, stenting, CABG) (Not associated
with acute event, such as MI)
4. Patients presenting with Acute Coronary Syndrome (ACS)
In all elective/scheduled case, prior to catheterization, a peripheral blood sample will
be obtained via an IV access line previously placed for the catheterization procedure.
In emergent cases of ACS, blood samples will be obtained in the same manner described
previously if possible. It is likely that in some cases, such as ST elevation myocardial
infarction (STEMI), this will not be possible based on clinical care priorities. In
these cases blood samples will be obtained within 24 hours after catheterization. These
blood samples will need to be obtained via venipuncture and will be clearly
labeled/recorded as being collected post-procedure. Blood samples will be frozen and
stored in a -80°C freezer in the Research Institute. Samples will be batch sent to
Baylor Medical Center to be tested for the presence of Wnt and Podocan molecules (Wnt-1,
Wnt-3, Dkk-1, Sclerostin, WIF-1, sFRP-1, sFRP-3) by measuring circulating levels via
ELISA Obstructive CAD (non-ACS) Group: It is expected that 900 stented patients will be
enrolled over 18-20 months. Justification of patient numbers is derived by specific aim
of attempting to establish prospective component of our study, which is the prediction
of restenosis. Given a current average incidence of restenosis between 10 to 15 % (DES
around 7% and BMS around 20% restenosis rate) this number should guarantee around 100
restenosis events out of 900 patients. This should give a realistic statistical chance
to detect a possible clinical predictive value of our variables. Participants who are
consented and sampled but who are found not to have obstructive CAD requiring stenting
will be maintained separately in the study database as a control group for future
analysis.
The following information will be collected from the baseline angiogram:
- syntax score in order to determine the coronary atherosclerotic burden
- PCI performed during baseline angiogram? If yes - what type of stent, location
Participant charts will be reviewed at 24 months post catheterization to collect
covariates (like age, sex, race/ethnicity, high blood pressure, obesity, smoking and
diabetes) and to monitor for the following events:
- Repeat cardiac catheterization
--Re-stenosis of stent placed at baseline angiogram
--Onset of new lesions
- Progression of lesions not treated at baseline angiogram
- New onset MI/ACS
- Recurrent MI/ACS
- Death due to known cardiovascular causation
CS Group:
The following information will be collected from the baseline angiogram:
- syntax score in order to determine the coronary atherosclerotic burden
- PCI performed during baseline angiogram? If yes - what type of stent, location
Participant charts will be reviewed at 24 months post catheterization to monitor for the
following events:
- Repeat cardiac catheterization --Re-stenosis of stent placed at baseline angiogram
--Onset of new lesions
--Progression of lesions not treated at baseline angiogram
- Recurrent MI/ACS
- Death due to known cardiovascular causation
Non- Obstructive/Stable CAD Group:
The following information will be collected from the baseline angiogram:
-syntax score in order to determine the coronary atherosclerotic burden
Participant charts will be reviewed at 24 months post catheterization to monitor for the
following events:
- Repeat cardiac catheterization
--Onset of new lesions
--Progression of lesions not treated at baseline angiogram
- New onset MI/ACS
- Death due to known cardiovascular causation
Normal Angiography (No CAD) Group:
Participant charts will be reviewed at 24 months post catheterization to monitor for the
following events:
- Repeat cardiac catheterization --Onset of new lesions
- Progression of lesions not treated at baseline angiogram
- New onset MI/ACS
- Death due to known cardiovascular causation
Comparison with Historical Samples: The principal investigator owns a collection of
historical tissue samples that have angiographically defined coronary target lesion
biopsies from clinical patients with stable angina and restenosis. The technique of DCA
(Directional Coronary Artherectomy), by which these samples were collected, is not
clinically done anymore, preventing the investigators from collecting these samples from
the current study participants. The current study participants will be grouped according
to exact same clinical criteria as the historic patients and hence represent comparable
clinical cohort. The expression of Podocan and Wnt effectory molecules (Wnt-1, Wnt-3,
Dkk-1, Sclerostin, WIF-1, sFRP-1, sFRP-3) in coronary artery lesions obtained by
Directional Coronary Artherectomy will be analyzed using immuno-histochemical staining
and quantitative histo-morphometric analysis comparing restenosis with Primary Stable
Coronary Artery Disease as published by the investigators (5). This comparison will
allow the investigators to examine the relationship between the level of the Podocan and
Wnt effectory molecules, coronary plaque physiology, and the study endpoint of disease
progression as evidenced by restenosis.
