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

Sponsor

University of New Mexico (Other)

Overall Status

Completed

CT.gov ID

NCT01764451

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH), University of California, San Francisco (Other)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cavernous Angioma, Familial Cerebral Cavernous Malformations Cerebral Cavernous Hemangioma	Drug: Simvastatin	Early Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Jan 1, 2016

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Simvastatin 20-40 mg tablet taken daily by mouth. Month 1: 20 mg; Months 2 and 3: 40 mg.	Drug: Simvastatin Other Names: Zocor
No Intervention: No Treatment

Arm

Intervention/Treatment

Experimental: Simvastatin

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

Drug: Simvastatin

Other Names:

Zocor

No Intervention: No Treatment

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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