- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04297033
Lovastatin for Treatment of Brain Arteriovenous Malformations
Lovastatin for Treatment of Brain Arteriovenous Malformations:a Double-blind, Placebo-controlled Randomized Trial
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Yong Cao, MD
- Phone Number: 100050 861067096510
- Email: caoyong6@hotmail.com
Study Locations
-
-
Beijing
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Beijing, Beijing, China, 100050
- Beijing Tiantan Hospital Affiliated to Capital Medical University
-
Contact:
- Yong Cao, MD
- Phone Number: 100050 861067096510
- Email: caoyong6@hotmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient must have BAVM diagnosed by MRI/MRA, CTA and/or angiogram
- BAVM deemed unsuitable for invasive treatment OR patient has elected to defer invasive treatment
- Patient must be 18 years of age or older
- Sign the informed consent
Exclusion Criteria:
- Patient has received prior BAVM interventional therapy (endovascular, surgical, radiotherapy)
- Patient has multiple-foci BAVMs
Patient has any form of arteriovenous or spinal fistulas
Previous diagnosis of any of the following -
- Patient was diagnosed with Vein of Galen type malformation
- Patient was diagnosed with cavernous malformation
- Patient was diagnosed with dural arteriovenous fistula
- Patient was diagnosed with venous malformation
- Patient was diagnosed with neurocutaneous syndrome such as cerebro-retinal angiomatosis (von Hippel-Lindau), encephalo-trigeminal syndrome (Sturge-Weber), or Wyburn-Mason syndrome
- Patient was diagnosed with BAVMs in context of moya-moya-type changes
- Patient was diagnosed with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)
- Contraindication to an HMG-coA-reductase inhibitor
- History of adverse reaction to HMG-coA-reductase inhibitors (rhabdomyolysis, hepatitis)
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
- Impaired liver function with aspartate transaminase (AST) or alanine transaminase (ALT) is more than twice limit of normal.
- Creatine kinase (CK) is more than twice limit of normal.
- Medications that interfere with the metabolism of lovastatin
- Gastrointestinal disease that would affect the ability to swallow or take oral medications or absorb them.
- 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)
- Patient has a history of chronic alcohol or drug abuse within 2 years prior to being recruited
- Patient has known allergy against iodine contrast agents
- Patient is pregnant or lactating
- Inability to provide informed consent.
- Participation in any clinical investigation within 2 months prior to dosing
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Lovastatin intervention
combination of 40mg/d 12m lovastatin and symptomatic treatment drugs as a treatment strategy for BAVM .
|
lovastatin 40mg/d 12m
|
PLACEBO_COMPARATOR: placebo
combination of placebo and symptomatic treatment drugs as a treatment strategy for BAVM
|
placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the incidence of stroke between two arms
Time Frame: 24 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in AVM volume from baseline MRI
Time Frame: baseline, 6 months, 12 months, 18 months, 24 months
|
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
|
Changes in the incidence of seizures and death between two arms
Time Frame: 24 months
|
Seizures and death are caused by lesions.
|
24 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Cardiovascular Abnormalities
- Neoplasms, Vascular Tissue
- Nervous System Malformations
- Vascular Malformations
- Intracranial Arterial Diseases
- Central Nervous System Vascular Malformations
- Congenital Abnormalities
- Hemangioma
- Arteriovenous Malformations
- Intracranial Arteriovenous Malformations
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Lovastatin
- L 647318
- Dihydromevinolin
Other Study ID Numbers
- AVM-lovastatin
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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