Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03364270 |
| Other study ID # |
Pro00047624 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
October 10, 2018 |
| Est. completion date |
May 31, 2020 |
Study information
| Verified date |
July 2022 |
| Source |
Cedars-Sinai Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to investigate the ability of a new investigational agent
compound [F-18] labeled RGD-K5 to detect unstable atherosclerotic plaque in the carotid
artery of subjects being considered for carotid endarterectomy (CEA), and to confirm this
ability through tissue analysis of samples of carotid artery plaques that will be collected
during the planned carotid surgery. [F-18] RGD-K5 is a radioactive tracer used in imaging to
detect active growth of new blood vessels and presence of macrophages. Patients with unstable
plaque may be prone to rupture of the plaque due to increase in macrophage activity and
growth of new blood vessels. [F-18] RGD-K5 is an investigational agent, which means that it
has not yet been approved by the US Food and Drug Administration (FDA).
Unstable atherosclerotic plaque that is prone to rupture is characterized by an increase in
the number of macrophages and enhanced angiogenesis. Both neovascular endothelium and
macrophages exhibit increased Alpha-v beta3 integrin expression. PET (Positron Emission
Tomography) imaging of [F-18] RGD-K5 uptake may identify carotid plaque with increased
inflammation and neovascularization and may therefore detect unstable plaque in participants
with carotid artery stenosis.
Prior to Dr. Tamarappoo's relocation to Cedars Sinai Medical Center (CSMC), 5 subjects were
enrolled at the Cleveland Clinic where PET-CT (Positron Emission Tomography - Computed
Tomography) was performed. 6 subjects will be scanned at Cedars using PET-MRI (Positron
emission tomography-magnetic resonance imaging). Based on preliminary data with PET-CTA, the
investigator strongly believes the study will be able to reproducibly detect significant
[F-18] RGD-K5 uptake in plaque from symptomatic patients. Ultimately, demonstrating
preferential [F-18] RGD-K5 uptake in symptomatic patients will significantly impact the way
in which patients with carotid plaque (at risk for stroke) are treated and it may prevent
unnecessary surgical and endovascular procedures in this population
Description:
The primary objectives of this exploratory study are:
- To assess the uptake of [F-18] RGD-K5 by carotid plaque with PET/MRI imaging in
participants prior to carotid endarterectomy and thereby determine if carotid plaque
that causes significant stenosis [in participants being considered for carotid
endarterectomy (CEA)] is characterized by increased integrin expression and enhanced
angiogenesis.
- To collect safety data of [F-18] RGD-K5 in participants with carotid atherosclerosis.
Potential subjects will be identified and approached during an inpatient or outpatient
clinical visit by a member of the research team. Potential subjects will be identified by
their treating physicians and referred to the researchers. Patients' private and identifiable
information will not be shared prior to receiving permission from the patient to do so
Summary of research procedures:
Physical exam and vital Signs:
Height, weight, temperature, heart rate and blood pressure will be checked before beginning
the imaging tests. Subjects' heart rate and blood pressure will be checked again after each
of the two PET/MRI images, and as needed.
Patients will also be asked about the presence of ICD, pacemaker or any metallic implants
that would not be compatible with the MRI magnet (presence of MRI non-compatible devices will
be an exclusion criteria)
Blood Test:
If labs have been done and the lab values meet the criteria to participate in this study, the
investigators will not need to collect these labs again on the day of testing. If these labs
have not been collected within 30 days prior to the research imaging tests, the investigators
will draw a tube of blood to check kidney function and other necessary blood values prior to
the research testing. Patients with a glomerular filtration rate (GFR) <40ml/min will be
excluded from the study.
Urine Pregnancy test:
This will only need to be done in female subjects of childbearing potential. This will need
to be checked prior to scheduling subjects' research imaging tests. If subjects' tests are
schedules more than 2 days (48 hours) since first checked, this test will need to be
rechecked on the day of subjects' research imaging testing.
ECG:
An ECG (electrocardiogram) will be done to assess subjects' heart rhythm before the testing
begins, and after each of the PET scans.
IV insertion:
A catheter will be inserted into subjects' arm. It is through this IV catheter that the dose
of [F-18] RGD-K5 will be given prior to imaging.
Research PET/MRI Imaging of the Carotid Arteries:
2 hours after receiving the dose of [F-18] RGD-K5 PET/MRI imaging of subjects' neck (carotid
arteries) will be performed. Subjects will be lying on subjects' back with a head fixation
device supporting subjects' head to prevent Subjects from moving subjects' head while the
images are taken. This scan will take about 30-45 minutes. Subjects will be permitted to get
up and move around between receiving the radiotracer and imaging. Subjects will be asked to
drink a glass of water before receiving the dose of [F-18] RGD-K5.
Histology and Immunohistochemistry:
During Subjects carotid endarterectomy(CEA) which is a clinically indicated procedure,
atherosclerotic plaque will be removed. A sample of this plaque will be collected and taken
to the histology laboratory at Cedars Sinai for analysis.
Follow Up phone call:
Subjects will be contacted by phone the day after subjects' PET scans to ask if Subjects have
had any medical problems and what medications Subjects have taken since the PET scan. If
Subjects were seen by a doctor to be evaluated for a medical problem, the investigators may
ask permission to contact the doctor or hospital to obtain copies of subjects' medical
records
Research poses greater than minimal risk
Anticipated benefits:
There is no personal benefit to participants by participating in this research study.
The knowledge to be gained from this research may be beneficial for other patients, society
or science.
The detection by the imaging protocol of unstable atherosclerotic plaque in the carotid
artery will not result in any change in their standard of care.
The potential benefit of the study to the patient is that it will allow the physician
treating the patient to know the entire extent of the carotid plaque, plaque composition and
will inform them of the anatomy of the carotid artery in question.
Furthermore, it will provide information about plaque in the contralateral carotid artery and
if that plaque has a high degree of inflammation. If a high inflammatory burden is noted in
the contralateral carotid artery, there will be more vigilance in monitoring these patients.
Summary of process by which confidentiality will be maintained:
Research records will be stored in a locked cabinet in a secure location Electronic research
records will be stored in a shared network folder on the CSMC network. The list linking the
assigned code number to the individual subject will be maintained separately from the other
research data. Only certified research personnel who are listed on the approved Institutional
Review Board (IRB) application will be given access to identifiable subject information.
Research related data and patient/subject information will never be stored on a researcher's
personal (private) computer or laptop. Study data will be coded upon abstraction so that
Direct Identifiers** are maintained separately from the data set.
Summary of data and safety monitoring plan:
The study will be monitored only by the study investigators and/or sponsor.
How does participation in the research differ from the receipt of standard care:
RISKS OF THE STUDY
As with any research study, there may be adverse events or side effects that are currently
unknown and it is possible that certain of these unknown risks could be permanent, serious or
life threatening. The study doctor will inform subjects of any significant new information
that is discovered during this trial.
Risks of the Study Drug Based upon the toxicity profile to be administered as a single dose,
the purity and impurity profile of [F-18] RGD-K5, no risk of adverse events is anticipated
for this study.
Radiation Risk:
- It is very unlikely that participants will see any harmful effects because of the
radiation exposure participants will receive from taking part in this study.
- At high levels of exposure, scientists agree that radiation can cause cancer. This
research study involves exposure to radiation from the RGDK5-PET scan. The total amount
of radiation exposure participants will receive is equivalent to a uniform whole-body
exposure of 0.8 rem. This is comparable to approximately three years' worth of radiation
exposure from typical environmental sources (about 0.3 rem per year, which includes
radon, natural background radiation, and cosmic rays). This is also comparable to 16% of
the maximum annual exposure for radiation workers (5 rem) allowed by the Nuclear
Regulatory Commission.
MRI is not associated with any radiation risk.
MRI non-compatible devices such as pacemakers, ICD (implantable cardioverter defibrillator)
and metallic implants may cause artifacts in imaging and device malfunction as well as local
tissue injury.
Contrast used for MRI is associated with minimal risk among patients who are free of
significant renal dysfunction.
When injected into the body, gadolinium contrast medium makes certain tissues, abnormalities
or disease processes more clearly visible on a magnetic resonance imaging scan. They are used
to improve the clarity of the scanned images or pictures of the body's internal structures.
Gadolinium contrast medium is given by intravenous injection.
The risk of gadolinium contrast is minimal in patients without severe renal disease.
The most common adverse effects of gadolinium agents are
- Itching of the skin (5%)
- Headache (4%)
- Nausea (4%)
- Very small risk of local pain
- Hypersensitivity (allergic reaction)
- Rarely (<1% of the time) it can cause low blood pressure and lightheadedness. This can
be treated immediately with IV fluids.
More serious allergic reactions that are life threatening are rare. Gadolinium is not safe
for people with late stage kidney disease or who have had a liver transplant.
Gadolinium-based contrast agents increase the risk for a rare, but serious adverse reaction,
called nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the
drugs. Patients with kidney disease are at increased risk of developing NSF. NSF may cause
skin thickening, joint pain and/or swelling, causing feelings of burning, itching and pain
that can be severe. In very rare cases, NSF can lead to lung and heart problems and may be
life threatening. Participants will have a blood test to measure kidney function and if the
blood test is abnormal, they will not be permitted to receive gadolinium.
There is a very small risk of mild headache and local pain. Rarely (<1% of the time) it can
cause low blood pressure and lightheadedness. This can be treated immediately with IV fluids.
More serious allergic reactions that are life threatening are rare. Gadolinium is not safe
for people with late stage kidney disease or who have had a liver transplant.
As with all research procedures and administration of study drugs, subjects will be monitored
at all times.
