PCSK9 Inhibition in Patients With Symptomatic Intracranial Atherosclerosis (PINNACLE)
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|ClinicalTrials.gov Identifier: NCT03507374|
Recruitment Status : Recruiting
First Posted : April 25, 2018
Last Update Posted : January 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Stroke Intracranial Atherosclerosis Intraplaque Hemorrhage||Drug: Alirocumab Drug: Placebo||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||PCSK9 Inhibition in Patients With Symptomatic Intracranial Atherosclerosis|
|Actual Study Start Date :||October 30, 2018|
|Estimated Primary Completion Date :||September 28, 2020|
|Estimated Study Completion Date :||September 28, 2021|
Placebo Comparator: Placebo Comparator
After review of eligibility criteria, 20 patients will be randomized to the placebo arm of the study where patient will administer one subcutaneous injection of placebo every two weeks for a total of 52 weeks. Additionally, per standard-of-care, patient will also be treated with atorvastatin 40-80 mg.
Placebo to be administered subcutaneously every 2 weeks identical to active drug (alirocumab)
Active Comparator: Active Comparator
After review of eligibility criteria, 20 patients will be randomized to receive the investigational treatment of alirocumab 150mg which will be administered subcutaneously with a single-dose pre-filled pen syringe every 2 weeks for a total of 52 weeks. Additionally, per standard-of-care, patient will also be treated with atorvastatin 40-80 mg
Alirocumab is approved by the FDA as a secondary treatment for high cholesterol for adults whose cholesterol can not be controlled by diet and/or statin treatment. Additionally, Alirocumab works to inhibit the PCSK9 protein.
Other Name: Praluent
- Vessel Wall MRI [ Time Frame: Day 1 and Day 365 ]Our primary outcome measures will be to assess the Vessel Wall MRI on Day 365 and compare it to day 1.The primary endpoint is nominal change in the composite percent atheroma volume (PAV) of the stroke parent artery and additional intra- or extracranial cerebrovasculature arteries with atherosclerosis (≥ 25% stenosis) from baseline to week 52. We will use measure PAV on vessel wall MRI (vwMRI), which evaluates all arteries from the aortic arch to the distal intracranial vasculature in a single scan. The primary endpoint will be analyzed for both: 1) the composite PAV of the stroke parent artery and any additional intra- or extracranial arteries that have at least 25% stenosis, and 2) separately for the PAV of the stroke parent artery. The PAV measurements will be performed using the validated MRI-PlaqueView software. Stenosis of the stroke parent artery and all additional arteries included in the composite PAV will be measured using standard methodology and also be evaluated as
- Post-Contrast Plaque Enhancement [ Time Frame: Day 1 ]Secondary endpoint 1 is post-contrast plaque enhancement for intracranial arteries and intraplaque hemorrhage for the carotid artery, which are determined by two experienced neuroradiologist raters. If there is disagreement, then a third rater serves as a tie-breaker. The signal intensity characteristics of both endpoints have been standardized in prior literature.
- Mechanism of Alirocumab's effect [ Time Frame: Day 1 and Day 365 ]To better understand the mechanism of alirocumab's effect on intra- and extracranial atherosclerosis, we will measure the endpoint of change in cholesterol markers [LDL-C, HDL-C, lipoprotein (a), apolipoprotein B, and triglyceride level]. The change in cholesterol markers will be correlated with the primary and secondary study endpoints on vwMRI. Cholesterol values will be measured at the baseline and comparison MRIs, which are 52 weeks apart. An additional exploratory outcome that we will measure is the composite endpoint of "recurrent stroke," which encompasses new symptomatic ischemic stroke, transient ischemic attack, or asymptomatic strokes that emerge between the study MRIs.
- Lab Assessment [ Time Frame: Baseline visit and Day 365 ]At both study MRIs, the study coordinator will collect two blood samples. One sample will be tested with an i-STAT for beta hCG and creatinine levels prior to the MRI. The second sample which will be sent to ARUP Laboratories for testing of LDL-C, HDL-C, triglycerides, apolipoprotein B, and lipoprotein (a), biomarkers of cardiovascular disease risk.
- Clinical Outcomes [ Time Frame: Baseline and Day 365 ]b) At both study visits (baseline vwMRI and follow-up vwMRI), a vascular neurologist blinded to treatment arm assignment will assess patients and their medical records for recurrent stroke. The neurologist will also have access to the "stroke characteristics" data from the neuroradiologist raters. The endpoint of recurrent stroke is defined both for the stroke parent artery and other arterial distributions in the cerebrovasculature.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03507374
|Contact: Adam de Havenon, MDfirstname.lastname@example.org|
|Contact: Scott McNally, MD, PhDemail@example.com|
|United States, Utah|
|University of Utah||Recruiting|
|Salt Lake City, Utah, United States, 84132|
|Contact: Adam de Havenon, MD 801-585-7575 firstname.lastname@example.org|
|Contact: Scott McNally, MD PHD 8015812121 email@example.com|
|Principal Investigator:||Adam de Havenon, MD||University of Utah|
|Principal Investigator:||Scott McNally, MD, PhD||University of Utah|