Lovastatin for Treatment of Brain Arteriovenous Malformations

March 5, 2020 updated by: Dr. Yong Cao, Beijing Tiantan Hospital

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

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

Study Overview

Status

Not yet recruiting

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

Interventional

Enrollment (Anticipated)

1244

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100050
        • Beijing Tiantan Hospital Affiliated to Capital Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

January 1, 2021

Primary Completion (ANTICIPATED)

June 1, 2024

Study Completion (ANTICIPATED)

June 1, 2024

Study Registration Dates

First Submitted

February 21, 2020

First Submitted That Met QC Criteria

March 3, 2020

First Posted (ACTUAL)

March 5, 2020

Study Record Updates

Last Update Posted (ACTUAL)

March 9, 2020

Last Update Submitted That Met QC Criteria

March 5, 2020

Last Verified

March 1, 2020

More Information

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.

Clinical Trials on Cerebral Arteriovenous Malformation

Clinical Trials on Placebo

3
Subscribe