Back to results

Lovastatin for Treatment of Brain Arteriovenous Malformations

Primary Purpose

Cerebral Arteriovenous Malformation

Status

Not yet recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Lovastatin

Placebo

About this trial

This is an interventional treatment trial for Cerebral Arteriovenous Malformation focused on measuring Cerebral Arteriovenous Malformation, Lovastatin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Beijing Tiantan Hospital Affiliated to Capital Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Lovastatin intervention

placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Changes in the incidence of seizures and death between two arms

Seizures and death are caused by lesions.

Full Information

NCT ID

NCT04297033

First Posted

February 21, 2020

Last Updated

March 5, 2020

Sponsor

Beijing Tiantan Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04297033

Brief Title

Lovastatin for Treatment of Brain Arteriovenous Malformations

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 1, 2021 (Anticipated)

Primary Completion Date

June 1, 2024 (Anticipated)

Study Completion Date

June 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Beijing Tiantan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cerebral Arteriovenous Malformation

Keywords

Cerebral Arteriovenous Malformation, Lovastatin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1244 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Lovastatin intervention

Arm Type

Experimental

Arm Description

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

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Lovastatin

Intervention Description

lovastatin 40mg/d 12m

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

placebo

Primary Outcome Measure Information:

Title

Change in the incidence of stroke between two arms

Description

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Change in AVM volume from baseline MRI

Description

Time Frame

baseline, 6 months, 12 months, 18 months, 24 months

Title

Changes in the incidence of seizures and death between two arms

Description

Seizures and death are caused by lesions.

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yong Cao, MD

Phone

861067096510

Ext

100050

caoyong6@hotmail.com

Facility Information:

Facility Name

Beijing Tiantan Hospital Affiliated to Capital Medical University

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100050

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yong Cao, MD

Phone

861067096510

Ext

100050

caoyong6@hotmail.com

12. IPD Sharing Statement

Learn more about this trial

Lovastatin for Treatment of Brain Arteriovenous Malformations

We'll reach out to this number within 24 hrs