Permeability MRI in Cerebral Cavernous Malformations Type 1 in New Mexico: Effects of Statins

Early Phase 1

Terminated

• Conditions: Cerebral Cavernous Malformations; Cavernous Angioma, Familial; Cerebral Cavernous Hemangioma
• Interventions: Drug: Simvastatin

• Registration Number: NCT01764451
• Lead Sponsor: University of New Mexico

Brief Summary

Cerebral cavernous malformations (CCMs) are clusters of abnormal blood vessels in the brain and spine. CCMs can bleed and cause strokes, seizures, and headaches. In some patients, CCMs affect the blood brain barrier (BBB). The BBB is the body's separation of blood and its contents in the brain from the brain tissue itself. Abnormal leakiness or permeability of this barrier can cause disease. We will measure the permeability (leakiness) of the BBB using a magnetic resonance imaging (MRI) technique called dynamic contrast-enhanced MRI (DCEMRI). The purpose of this study is to look at whether statin medications change the permeability (leakiness) of the blood brain barrier in CCM patients. Statin medications are used to lower cholesterol levels and prevent heart attack and stroke. In addition, this medication may decrease the risk of brain hemorrhage or bleeding in patients with CCM. This study will examine whether the permeability of the BBB changes following the administration of simvastatin for three months.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03
• Study First Submitted: 2013-01-07
• Study First Submitted QC: 2013-01-07
• Study First Posted: 2013-01-09
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-08
• Last Update Posted: 2024-03-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Diagnosis of cerebral cavernous malformations-common Hispanic mutation (CCM1-CHM)
• Must be willing to travel to the University of New Mexico in Albuquerque, NM for 5 visits over the course of three months.

Exclusion Criteria

• Incarceration
• Unable to pass MRI safety screening (pregnant females, claustrophics, or those with certain metallic items implanted in their bodies)
• Low kidney function or transplants, an eGFR below 60 mL/min
• Currently taking statin medications or have taken statin medications in the past 6 months
• Known allergy or intolerance to statins
• Known allergy or intolerance to gadolinium
• Liver dysfunction at baseline, AST > 47 and/or ALT > 49
• Consumption of large quantities of alcohol, men who consume more than 2 daily drinks and women who consume more than one daily drink
• CK level of 232 or higher
• Triglycerides greater than or equal to 500.
• Medications: gemfibrozil, cyclosporine, danazol, itraconazole, ketoconazole, posaconazole, ethromycin, clarithomycin, telithromycin, HIV protease inhibitors, nefazoldone, amiodarone, verapamil, dilitiazem, amlodipine, or ranalazine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Simvastatin	Simvastatin	20-40 mg tablet taken daily by mouth. Month 1: 20 mg; Months 2 and 3: 40 mg.

Primary Outcome Measures

Name	Time	Method
Change in blood brain barrier permeability over three months for the treatment group compared to the control group.	Baseline, Three Months	We will measure the change in blood brain barrier permeability with dynamic contrast enhanced MRI from baseline to three months. We will compare the change in permeability for a group of CCM patients placed on statin medication (treatment group) with a group of CCM patients not on statin medication (control group).

Secondary Outcome Measures

Name	Time	Method
Correlation of physiologic permeability data with anatomic lesion data	Baseline, Three months	Use dynamic contrast-enhanced MRI to detect abnormalities in brain permeability in CCM patients and correlate with anatomic lesion information.

Trial Locations

Locations (1)

University of New Mexico Health Sciences Center; 🇺🇸 Albuquerque, New Mexico, United States