Clinical trial NCT04297033: Lovastatin for Treatment of Brain Arteriovenous Malformations
Official title: Lovastatin for Treatment of Brain Arteriovenous Malformations:a Double-blind, Placebo-controlled Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cerebral Arteriovenous Malformation
Keywords: Cerebral Arteriovenous Malformation, Lovastatin
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2020-03-05
Enrollment: 1244
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this pilot study is to evaluate the disease-modifying efficacy of lovastatin in patients with brain arteriovenous malformation.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in the incidence of stroke between two arms
timeFrame: 24 months
Secondary outcomes:
measure: Change in AVM volume from baseline MRI
timeFrame: baseline, 6 months, 12 months, 18 months, 24 months
measure: Changes in the incidence of seizures and death between two arms
timeFrame: 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital Affiliated to Capital Medical University
state: Beijing
Study officials:
References: