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

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.

Study Overview

• Status: Terminated
• Conditions: Cerebral Cavernous Malformations; Cavernous Angioma, Familial; Cerebral Cavernous Hemangioma
• Intervention / Treatment: Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood brain barrier permeability over three months for the treatment group compared to the control group.	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).	Baseline, Three Months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); University of California, San Francisco
• Investigators: Principal Investigator: Leslie A Morrison, MD, University of New Mexico; Principal Investigator: Blaine Hart, MD, University of New Mexico

Publications and helpful links

Helpful Links

• Angioma Alliance is an organization by and for those affected by cavernous angiomas and their loved ones, health professionals, and researchers.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 7, 2013
• First Submitted That Met QC Criteria: January 7, 2013
• First Posted (Estimated): January 9, 2013

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Hispanic
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Cardiovascular Abnormalities; Neoplasms, Vascular Tissue; Nervous System Malformations; Vascular Malformations; Central Nervous System Vascular Malformations; Cavernous Sinus Syndromes; Congenital Abnormalities; Hemangioma; Hemangioma, Cavernous, Central Nervous System; Hemangioma, Cavernous; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: BVMC 6205; U54NS065705 (U.S. NIH Grant/Contract)