Permeability MRI in Cerebral Cavernous Malformations type 1 in New Mexico: Effects of Statins
Individuals with Cerebral Cavernous Malformations (CCMs) have clusters of abnormally enlarged blood vessels in the brain and spinal cord. These abnormal clusters can bleed and cause headaches, seizures, and strokes. The Common Hispanic Mutation (CCM1-CHM) is an inherited form of CCMs frequently seen in Hispanic families of the southwestern United States. In some patients, CCMs affect the blood brain barrier (BBB). The BBB is a protective barrier that filters blood going into the brain and spinal cord. Abnormal leakiness or permeability (ability to pass through) of this barrier can cause disease. This research is looking at whether simvastatin (a drug used to lower cholesterol levels and prevent heart attack and stroke, also called statin medication) also change the leakiness of the blood brain barrier in patients with CCM. In studies of mice with CCM, use of statin medications strengthened the blood vessels and prevented leakiness. We will look at the permeability of the BBB using a magnetic resonance imaging (MRI) technique called dynamic contrast-enhanced MRI (DCEMRI). This technique measures leakiness but does not change it.
The research goals are to:
- Use DCEMRI to detect abnormalities in brain permeability in CCM patients and show relationships with lesion information in the brain,
- Compare change in permeability over a 3-month period in a group of CCM patients placed on statin medication with change in permeability for a control group of CCM patients not on statin medication
- Develop plans for future clinical trials of statin medication comparing outcome (number of hemorrhages, worsening of epilepsy) using permeability as a measure.
About this Study
In this study, 30 participants will be randomly assigned to either simvastatin or no treatment for three months. Baseline laboratory tests will be used to screen individuals for elevated levels of LDL cholesterol and to identify people who would need to take cholesterol lowering medications (simvastatin).
Participants will complete 5 visits at UNM within three months and be in contact with a member of the research team every 4-6 weeks during that time.
- The first visit includes consent, blood draw, and medication review.
- The second visit includes a MRI with a contrast agent called gadolinium. Participants assigned by chance (like a flip of a coin) to receive simvastatin will begin the medication within three days of their first MRI. Medication will be taken daily for three months and the dosage will be recorded daily on a medication diary.
- The third visit includes a blood draw for those participants taking simvastatin to test for liver function.
- The fourth visit includes another blood draw and review of the medication and seizure diary.
- The fifth and final visit includes a second MRI with gadolinium.
At these visits, you will also be asked to:
- Have vital signs taken at three visits
- Provide information about your medical history and surgical history
- Fill out a questionnaire about your quality of life
- Take a urine pregnancy test prior to each MRI (if you are a female of childbearing age)
In addition, you will be asked to:
- Keep a diary of seizures during the study
- Take 1 simvastatin pill a day at bedtime (for those assigned to the simvastatin group)
- Keep a medication diary (for those assigned to the simvastatin group)
To be eligible to participate, you must:
- Have a confirmed diagnosis of CCM1-CHM by DNA testing.
- Be 18 years old or older.
- Pass an MRI safety test. To pass the MRI Safety test,
- You must not be pregnant.
- You must be able to tolerate enclosed spaces (not be claustrophobic)
- You must not have any metallic items implanted in your body).
- Travel to the University of New Mexico for 5 visits over the course of 3 months.
- Have an indication for statin treatment based on the National Cholesterol Education Program (NCEP) ATPIII guidelines, which includes one of the following:
- An LDL cholesterol level ≥ 160.
- An LDL cholesterol level of 130-159 AND two or more risk factors such as cigarette smoking, hypertension or low HDL cholesterol AND a 10-year coronary heart disease risk of 10-20%.
- An LDL cholesterol level of 101-159 AND coronary heart disease, diabetes mellitus, symptomatic carotic artery disease, peripheral arterial disease, or abdominal aortic aneurysm OR a 10-year coronary heart disease equivalent risk > 20%
You are not eligible to participate if you:
- Are incarcerated.
- Are unable to pass a MRI safety screening test (this includes pregnancy in females, claustrophobic patients, and those with any metallic items implanted in their bodies).
- Are unable to tolerate MRI without conscious sedation or general anesthesia.
- Are younger than 18 years old.
- Have low kidney function or kidney transplants.
- Are currently taking statin medications (e.g., atorvastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin) or have taken statin medications in the past six months.
- Have a known allergy or intolerance to statins or gadolinium.
- Have liver dysfunction, defined as having an AST > 47 and/or an ALT > 49.
- Consume large quantities of alcohol, defined for men as more than two daily drinks and for women as more than one daily drink.
- Have a creatinine kinase (CK) level of 232 or higher.
- Have triglyceride levels ≥ 500.
How to participate
In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.