Immune cell activation following ischemic cerebrovascular events: a multimodal exploratory study

The innate immune system importantly contributes to the pathophysiology of
atherosclerotic cardiovascular disease, such as stroke and myocardial
infarction. Recurrence rate is particularly high in the first months/year after
a first ischemic event. Animal studies have shown that acute myocardial
infarction or stroke can activate the innate immune system through effects on
bone marrow myeloid progenitors. We hypothesize that this immune system
activation drives the high recurrence rate. The current proposal therefore aims
to explore the innate immune cell phenotype in patients immediately following
an ischemic cerebrovascular event, both in the bone marrow, the circulation,
and the atherosclerotic plaque. Knowledge on this mechanism and on how this
mechanism can be non-invasively detected by PET scanning, will contribute to
the development of novel pharmacological strategies to reduce cardiovascular
disease.

To explore innate immune cell composition, function and proliferation in the
circulation, bone marrow, and atherosclerotic plaque in patients scheduled for
elective carotid endarterectomy because of recent ischemic stroke or transient
ischemic attack and relate these findings to FDG-PET imaging of the carotid
plaque and bone marrow.

This study is an exploratory observational study in the Radboud university
medical center.

As discussed in paragraph 11.4 (in the Research Protocol), the venous blood
withdrawal of 40 mls of blood, the bone marrow aspiration, and the FDG-PET do
not pose significant health risks for the participants.

We will take various measures to reduce the risk as much as possible.
The radiation dose for the PET-CT scan is in risk category IIb. Our study
deliver the required level of benefit (acquisition of knowledge, directly aimed
at prevention or cure of disease). There are no known side effects with the
use of this radiotracer. As far as the PET aspects of the imaging are
concerned, the minimum dose of FDG that provides adequate quantification will
be used in all subjects.
All imaging studies will be interpreted by a nuclear medicine phycisian and a
report of the findings will be provided which may influence the future care of
the subject in line with standard clinical practice. Since some of these
participants would not normally have undergone PET, it is possible that their
participation in the study could lead to additional clinical workup that would
not have occurred without their participation in this study. In some cases,
these findings may lead to discovery of additional disease, thus benefiting the
participant. If incidental findings unrelated to the study are seen on the
research images which should prompt further medical or imaging workup, the
subject*s physician will be contacted and recommendations for further workup,
will be made. No clinical decisions will be based on the research images

For venipuncture, risks will be minimized by having highly experienced and
qualified nurses or physicians performing the procedure (venipuncture) and a
highly experienced physician assistant from the department of haematology to
perform the bone marrow aspiration.

Given the importance of the data that will be derived from this study, we feel
the minimal risk described under 11.4 is proportional.