Lovastatin for Treatment of Brain Arteriovenous Malformations
Paraules clau
Resum
Descripció
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.
Dates
| Darrera verificació: | 02/29/2020 |
| Primer enviat: | 02/20/2020 |
| Inscripció estimada enviada: | 03/02/2020 |
| Publicat per primera vegada: | 03/04/2020 |
| Última actualització enviada: | 03/04/2020 |
| Publicació de l'última actualització: | 03/08/2020 |
| Data d'inici de l'estudi real: | 12/31/2020 |
| Data estimada de finalització primària: | 05/31/2024 |
| Data estimada de finalització de l’estudi: | 05/31/2024 |
Condició o malaltia
Intervenció / tractament
Drug: Lovastatin intervention
Drug: placebo
Fase
Grups de braços
| Braç | Intervenció / tractament |
|---|---|
| Experimental: Lovastatin intervention combination of 40mg/d 12m lovastatin and symptomatic treatment drugs as a treatment strategy for BAVM . | Drug: Lovastatin intervention lovastatin 40mg/d 12m |
| Placebo Comparator: placebo combination of placebo and symptomatic treatment drugs as a treatment strategy for BAVM | Drug: placebo placebo |
Criteris d'elegibilitat
| Edats elegibles per estudiar | 18 Years Per a 18 Years |
| Sexes elegibles per estudiar | All |
| Accepta voluntaris saludables | Sí |
| Criteris | 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 |
Resultat
Mesures de resultats primaris
1. Change in the incidence of stroke between two arms [24 months]
Mesures de resultats secundaris
1. Change in AVM volume from baseline MRI [baseline, 6 months, 12 months, 18 months, 24 months]
2. Changes in the incidence of seizures and death between two arms [24 months]
