Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT04240119 |
| Other study ID # |
Pro00046030 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 2012 |
| Est. completion date |
December 31, 2030 |
Study information
| Verified date |
February 2023 |
| Source |
Cedars-Sinai Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Intracranial atherosclerosis (ICAS) is the most common cause of stroke worldwide. It carries
a worse prognosis than other stroke etiologies, with an annual rate of recurrent stroke and
death of 15% despite intensive medical management, and as high as 35% in certain populations.
Overall, treatment and prevention of stroke due to ICAS has been unsuccessful. While two
recent clinical trials have shown modest improvement in the efficacy of intensive medical
treatment, these trials were terminated early given the elevated rate of complications,
stroke, and death in the interventional arms. In fact, intensive medical management appears
to reduce the risk of embolism; however, medical management alone does not address the
progression of intracranial arterial stenosis or the pathophysiologic components of
hypoperfusion and poor collateral circulation.
Levels and types of various angiogenic factors in the blood and tissues have been proposed to
be predictive of patient outcome after ischemic stroke and treatment for stroke. This study
therefore pursues a new paradigm to investigate responses to ICAS treatment from the
perspective of cerebral collateral vessel generation and the role of angiogenic factors.
Specifically, pro- and anti-angiogenic factors in patients with ICAS are evaluated at
baseline and longitudinally in response to both medical and surgical treatment. For this we
have developed methodologies for the isolation and measurement of these growth factors in
plasma of patients with ICAS. These methodologies will enable us to obtain a detailed
understanding of the variation and dynamic properties of local and circulating angiogenic
factors over time in response to medical and surgical treatment, and their association to
outcome phenotypes. This analysis is complemented by studies of angiographic development of
neovascularization. If successful, this study will help to better understand the role of
angiogenesis in ICAS and create a foundation from which to explore therapeutic treatments for
ICAS which harness the natural processes of angiogenesis.
Description:
Intracranial atherosclerosis (ICAS) is the most common cause of stroke worldwide. It accounts
for at least 10% of all strokes in the United States and as much as 67% in countries with
predominantly Asian, Hispanic, and Black populations. ICAS carries a worse prognosis than
other stroke etiologies, with an annual rate of recurrent stroke and death of 15% despite
intensive medical management, and as high as 35% in certain populations. Recent randomized
controlled clinical trials have shown that angioplasty with stenting and bypass surgery fail
to improve outcomes in patients with ICAS.
Overall treatment and prevention of stroke due to ICAS has been unsuccessful. The results of
two recent clinical trials exploring interventions for the management of cerebrovascular
occlusive disease-bypass surgery (Carotid Occlusion Surgery Study [COSS]) and angioplasty and
stenting (SAMMPRIS)-have shown modest improvement in the efficacy of intensive medical
treatment. However, both trials were terminated early given the elevated rate of
complications, stroke, and death in the interventional arms. In the medical arms of COSS and
SAMMPRIS, the rates of stroke and death at two years were 21% and 15%, respectively.
Intensive medical management appears to reduce the risk of embolism; however, medical
management alone does not address the progression of intracranial arterial stenosis or the
pathophysiologic components of hypoperfusion and poor collateral circulation. Patients with
prior stroke had an even higher rate of stroke, 35%.
Levels and types of various angiogenic factors in the blood and tissues have been proposed to
be predictive of patient outcome after ischemic stroke and treatment for stroke. This study
therefore pursues a new paradigm to investigate responses to ICAS treatment from the
perspective of cerebral collateral vessel generation and the role of angiogenic factors.
Specifically, pro- and anti-angiogenic factors in patients with ICAS are evaluated at
baseline and longitudinally in response to both medical and surgical treatment. For this we
have developed methodologies for the isolation and measurement of these growth factors in
plasma of patients with ICAS. These methodologies will enable us to obtain a detailed
understanding of the variation and dynamic properties of local and circulating angiogenic
factors over time in response to medical and surgical treatment, and their association to
outcome phenotypes. This analysis is complemented by studies of angiographic development of
neovascularization. If successful, this study will help to better understand the role of
angiogenesis in ICAS and create a foundation from which to explore therapeutic treatments for
ICAS which harness the natural processes of angiogenesis.
