Lovastatin for Treatment of Brain Arteriovenous Malformations

NCT ID: NCT04297033

Last Updated: 2020-03-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 1244 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2024-06-01

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.

Conditions

Cerebral Arteriovenous Malformation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lovastatin intervention

combination of 40mg/d 12m lovastatin and symptomatic treatment drugs as a treatment strategy for BAVM .

Group Type: EXPERIMENTAL

Lovastatin

Intervention Type: DRUG

lovastatin 40mg/d 12m

placebo

combination of placebo and symptomatic treatment drugs as a treatment strategy for BAVM

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo

Interventions

Lovastatin

lovastatin 40mg/d 12m

Intervention Type: DRUG

Placebo

placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dr. Yong Cao

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing Tiantan Hospital Affiliated to Capital Medical University

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Yong Cao, MD

Role: CONTACT

caoyong6@hotmail.com

861067096510 ext. 100050

Facility Contacts

Yong Cao, MD

Role: primary

caoyong6@hotmail.com

861067096510 ext. 100050

Other Identifiers

AVM-lovastatin

Identifier Type: -

Identifier Source: org_study_id