Clinical Trial: Atorvastatin Therapy in Cerebral Cavernous Malformation: A Proof of Concept Phase I/II Trial

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase I-II Randomized, Placebo-Controlled, Single-Blinded, Single-Site Clinical Trial of Atorvastatin in the Treatment of Cerebral Cavernous Malformation

Brief Summary: The study aims to demonstrate that extended course atorvastatin therapy reduces lesional iron deposition without increasing the risk of rebleeding (acute hemorrhage) in patients with cerebral cavernous malformation (CCM). Subjects will be randomized to daily atorvastatin (20,40 or 80mg PO) or placebo and followed for 36 months, or until a clinically overt CCM hemorrhage or attrition from drug related adverse events. Subjects will undergo a total of four MRI scans with biomarker studies, and serial clinical assessments.

Detailed Summary: The proposed study is a prospective phase I/II randomized, placebo-controlled, single-blinded, single-site clinical trial. Sixty CCM subjects will be randomized in a 2:1 fashion to receive either atorvastatin (40 mg PO) or placebo, All subjects will undergo baseline and three interval MRI studies at 6, 18 and 36 months throughout the three-year study period. Systematic dose escalation regime will be followed based on lesional and brain vascular permeability assessed by dynamic contrast enhanced quantitative perfusion (DCEQP). At the six month MRI scan, subjects with > 30% reduction in either lesional or brain permeability will be continued on the same dose. If neither lesional or background brain permeability exhibit >30% reduction, the dose will be escalated to 80 mg in the absence of any side effects. Enrolled subjects and investigators assessing dose related DCEQP and iron deposition in lesions by Quantitative Susceptibility Mapping (QSM) will be blinded to treatment group allocation.
Sponsor: University of Chicago

Current Primary Outcome: lesional iron concentration [ Time Frame: End of study (36-month) MRI scan ]

Lesional iron load measured by QSM protocol during the end of trial visit.


Original Primary Outcome: Same as current

Current Secondary Outcome: Rebleeding Rate [ Time Frame: Three years ]

Number of recurrent hemorrhagic events on Atorvastatin Vs Placebo


Original Secondary Outcome: Same as current

Information By: University of Chicago

Dates:
Date Received: November 9, 2015
Date Started: July 2016
Date Completion: June 2021
Last Updated: March 4, 2016
Last Verified: March 2016