Clinical trial NCT03507374: PCSK9 Inhibition in Patients With Symptomatic Intracranial Atherosclerosis
Official title: PCSK9 Inhibition in Patients With Symptomatic Intracranial Atherosclerosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Stroke
Intracranial Atherosclerosis
Intraplaque Hemorrhage
Keywords: Stroke
alirocumab
Intracranial Atherosclerosis
Intraplaque Hemorrhage
atorvastatin
praluent
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-04-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be a randomized double blind placebo-controlled pilot study using a repeated measures design in which participants with acute ischemic stroke and intracranial atherosclerotic disease are randomized to either drug or placebo.

Detailed description: The purpose of this study will be a dataset that lays the foundation for a randomized controlled trial of PCSK9 inhibition in intracranial atherosclerotic disease (ICAD) patients, designed to show a reduction in the primary endpoint of ischemic stroke recurrence. Such a trial would provide evidence for the utility of alirocumab to prevent recurrent stroke in ICAD. While we are proposing future studies to reduce recurrent ICAD stroke risk, it should be noted that, in the long term, our research may lead to effective primary ICAD stroke risk reduction through PCSK9 inhibition in patients at high risk of stroke identified through asymptomatic stenosis, post-contrast plaque enhancement (PPE) or intraplaque hemorrhage (IPH) on vwMRI.

Eligibility criteria: Inclusion Criteria:

* Adult patients, ≥ 18 years of age
* Ischemic stroke (≤ 1 month from onset) in one major vascular territory on diffusion-weighted MRI
* ICAD plaque of a "major intracranial artery," causing \>25% and \<99% stenosis
* Eligible arteries: vertebral (V4), basilar, PCA (P1, P2), MCA (M1, M2), terminal ICA, and ACA (A1)
* Able to tolerate high-dose statin (atorvastatin 40-80 mg)

Exclusion Criteria:

* Stroke mechanism other than ICAD, including history of atrial fibrillation, hypercoagulability, ipsilateral arterial dissection or carotid stenosis \>50%, and rare causes of stroke such as vasculitis or CADASIL
* Bihemispheric stroke or simultaneous stroke in the anterior and posterior circulation
* Positive pregnancy test
* Gadolinium or PCSK9 inhibitor allergy
* Acute or chronic kidney disease with eGFR\<30 ml/min/1.73m2
* Pacemaker or other MRI contraindications per American College of Radiology guidelines33
* Inability to return for 1-year follow-up clinic visit and vwMRI

Primary outcomes:
measure: Vessel Wall MRI
timeFrame: Day 1 and Day 365
Secondary outcomes:
measure: Post-Contrast Plaque Enhancement
timeFrame: Day 1
Other outcomes:
measure: Mechanism of Alirocumab's effect
timeFrame: Day 1 and Day 365
measure: Lab Assessment
timeFrame: Baseline visit and Day 365
measure: Clinical Outcomes
timeFrame: Baseline and Day 365
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Adam de Havenon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Scott McNally, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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