Lovastatin for Treatment of Brain Arteriovenous Malformations

Cerebral Arteriovenous Malformation Clinical Trial

Official title:

Lovastatin for Treatment of Brain Arteriovenous Malformations:a Double-blind, Placebo-controlled Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04297033
• Other study ID #: AVM-lovastatin
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2021
• Est. completion date: June 1, 2024

Study information

• Verified date: March 2020
• Source: Beijing Tiantan Hospital
• Contact: Yong Cao, MD
• Phone: 861067096510
• Email: caoyong6[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1244
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arteriovenous Malformations
• Cerebral Arteriovenous Malformation
• Congenital Abnormalities
• Hemangioma
• Intracranial Arteriovenous Malformations

Intervention

Drug:
• Lovastatin
lovastatin 40mg/d 12m
• Placebo
placebo

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital Affiliated to Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the incidence of stroke between two arms	Stroke is defined as a clinically symptomatic event (any new focal neurological deficit, seizure, or new-onset headache) that is associated with imaging findings of haemorrhage or infarction. Haemorrhage is defined as fresh intracranial blood on head CT or MRI, or in the cerebrospinal fluid. Infarction is defined as a new ischaemic lesion on cranial CT or MRI (diffusion-weighted, T2-weighted, or fluid-attenuated inversion recovery MRI).	24 months
Secondary	Change in AVM volume from baseline MRI	The volume of arteriovenous malformations will be measured by using MRIcron. The brain arteriovenous malformations will be traced directly on the brain MRIs using MRIcron. Masks of the brain arteriovenous malformations will be drawn on each patient's T1 image in native space by board-certified neurosurgeons, who are blinded to the patients' clinical information. Then, the volume of arteriovenous malformations can be calculated by MRIcron.	baseline, 6 months, 12 months, 18 months, 24 months
Secondary	Changes in the incidence of seizures and death between two arms	Seizures and death are caused by lesions.	24 months