Lovastatin for Treatment of Brain Arteriovenous Malformations
Lovastatin for Treatment of Brain Arteriovenous Malformations
The purpose of this pilot study is to evaluate the disease-modifying efficacy of lovastatin
 in patients with brain arteriovenous malformation.
Brain arteriovenous malformations are lesions that consist of multiple arteries and veins,
 connecting as a fistula without intervening normal capillary bed. As the disease progresses,
 the lesion may cause several adverse clinical events including stroke, seizure or even death.
 For patients with BAVM deemed unsuitable for invasive treatment or who has elected to defer
 invasive treatment, it is essential to take effective medical management.

 Lovastatin possesses antiinflammatory and antiproliferative actions in human endothelial and
 vascular smooth muscle cells independent of its lipid-lowing action. These findings suggest
 that lovastatin may be beneficial for maintaining vascular stability, which may contribute to
 slowing down the progression of the disease and reducing the incidence of adverse clinical
 events.

 The purpose of this pilot study is to evaluate the safety and disease-modifying efficacy of
 lovastatin in patients with BAVMs. Participants will be randomly assigned to receive either
 combination of lovastatin and symptomatic treatment drugs or combination of placebo and
 symptomatic treatment drugs. Patients will have post-dose safety follow-up visit at 1, 3, 6,
 and 12 months after the study begins. The changes in clinical outcomes, including lesion
 volume changes and the rate of stroke, seizure or death, will be evaluated in a period of 2
 years.
Inclusion Criteria:

 1. Patient must have BAVM diagnosed by MRI/MRA, CTA and/or angiogram

 2. BAVM deemed unsuitable for invasive treatment OR patient has elected to defer invasive
 treatment

 3. Patient must be 18 years of age or older

 4. Sign the informed consent

 Exclusion Criteria:

 1. Patient has received prior BAVM interventional therapy (endovascular, surgical,
 radiotherapy)

 2. Patient has multiple-foci BAVMs

 3. Patient has any form of arteriovenous or spinal fistulas

 Previous diagnosis of any of the following -

 4. Patient was diagnosed with Vein of Galen type malformation

 5. Patient was diagnosed with cavernous malformation

 6. Patient was diagnosed with dural arteriovenous fistula

 7. Patient was diagnosed with venous malformation

 8. Patient was diagnosed with neurocutaneous syndrome such as cerebro-retinal
 angiomatosis (von Hippel-Lindau), encephalo-trigeminal syndrome (Sturge-Weber), or
 Wyburn-Mason syndrome

 9. Patient was diagnosed with BAVMs in context of moya-moya-type changes

 10. Patient was diagnosed with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)

 11. Contraindication to an HMG-coA-reductase inhibitor

 12. History of adverse reaction to HMG-coA-reductase inhibitors (rhabdomyolysis,
 hepatitis)

 13. Use of any cholesterol lowering medication in the previous 12 weeks

 Uncontrolled medical conditions that could potentially increase the risk of toxicities
 or complications of this treatment

 14. Impaired liver function with aspartate transaminase (AST) or alanine transaminase
 (ALT) is more than twice limit of normal.

 15. Creatine kinase (CK) is more than twice limit of normal.

 16. Medications that interfere with the metabolism of lovastatin

 17. Gastrointestinal disease that would affect the ability to swallow or take oral
 medications or absorb them.

 18. End stage renal disease (creatinine clearance eGFR <30 mL/min) or history of severe
 cardiac disease (angina, myocardial infarction or cardiac surgery in preceding two
 years)

 19. Patient has a history of chronic alcohol or drug abuse within 2 years prior to being
 recruited

 20. Patient has known allergy against iodine contrast agents

 21. Patient is pregnant or lactating

 22. Inability to provide informed consent.

 23. Participation in any clinical investigation within 2 months prior to dosing