ExAblate Blood Brain Barrier Disruption (BBBD) for Planned Surgery in Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03322813
Recruitment Status : Not yet recruiting
First Posted : October 26, 2017
Last Update Posted : February 22, 2018
Information provided by (Responsible Party):

Brief Summary:
This study is designed to assess the safety and feasibility of using the ExAblate, Type 2 to temporarily disrupt the blood brain barrier in non-enhancing suspected glioblastomas. The ExAblate Model 4000 Type-2 is intended for use as a tool to disrupt the BBB.

Condition or disease Intervention/treatment
Glioblastoma Device: ExAblate 4000 - Type 2

Detailed Description:
This study is a prospective, single-arm, non-randomized, open-label feasibility study to evaluate the safety of focal BBBD using the ExAblate® 4000 Type 2 system. Up to 15 subjects with suspected glioblastoma who are scheduled to undergo brain tumor resection may be recruited for the study. Only patients that have a non-enhancing tumor components in a non-eloquent region of the planned standard-of-care resection volume will be eligible. Up to 4 centers may participate in this study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Safety and Feasibility of Exablate Model 4000 Type-2 to Temporarily Mediate Blood-Brain Barrier Disruption (BBBD) in Patients With Suspected Glioblastoma in the Setting of Planned Surgical Interventions
Anticipated Study Start Date : March 2018
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: ExAblate 4000 - Type 2
ExAblate BBBD
Device: ExAblate 4000 - Type 2
Using ExAblate Model 4000 Type-2 to temporarily disrupt the blood brain barrier in non-enhancing glioblastomas undergoing resection
Other Name: ExAblate BBBD

Primary Outcome Measures :
  1. Device and procedure related adverse events [ Time Frame: At the time of the ExAblate MRgFUS procedure ]
    The number and severity of device and BBBD procedure related adverse events will be evaluated.

Secondary Outcome Measures :
  1. Feasibility of BBB opening [ Time Frame: At the time of the ExAblate MRgFUS procedure and 24 hours post-procedure ]
    The extent and reversibility of BBB opening will be determined by the degree of contrast enhancement seen on post-procedure MRI with contrast agent

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or Female between 21-85 years of age.
  2. Able and willing to give informed consent, or has delegated this to a substitute decision maker.
  3. Subjects with suspected glioblastoma on pre-operative brain imaging scans including non-enhancing MRI tumor components in non-eloquent regions that are within the planned surgical resection volume.
  4. Planned surgical resection volume with ≤8 cm3
  5. Karnofsky Performance Score 70-100
  6. Able to communicate sensations during the ExAblate® BBBD procedure.

Exclusion Criteria:

  1. MRI or clinical findings of:

    • Active or chronic infection(s) or inflammatory processes
    • Acute or chronic hemorrhages, specifically any lobar microbleeds, and no siderosis, amyloid angiopathy, or macrohemorrhages
    • Intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis
    • Evidence of tumor-related calcification, cyst, or hemorrhage
    • Midline shift or evidence of subfalcine, uncal, or tonsillar herniation on pre-operative imaging
  2. More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp
  3. Clips, shunts, or any metallic implanted objects in the skull or the brain or the presence of unknown MR unsafe devices anywhere within the body.
  4. Significant cardiac disease or unstable hemodynamic status
  5. Uncontrolled hypertension (systolic > 150 and diastolic BP > 100 on medication)
  6. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk of hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure
  7. History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage
  8. Abnormal coagulation profile (Platelets < 100,000), PT (>14) or PTT (>36), and INR > 1.3.
  9. No lacunar lesions or evidence of increased risk of bleeding.
  10. Known cerebral or systemic vasculopathy
  11. Significant depression and at potential risk of suicide
  12. Known sensitivity/allergy to gadolinium, or other intravascular contrast agents
  13. History of seizure disorder or epilepsy which could be worsened by disruption of the blood brain barrier.
  14. Evidence of worsening neurological function
  15. Dexamethasone dose ≥ 16mg daily or equivalent steroid dose
  16. History of drug or alcohol disorder which have a higher risk for seizures, infection and/or poor executive functioning.
  17. Positive HIV status, which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis
  18. Potential blood-borne infections which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.
  19. Any contraindications to MRI scanning, including:

    • Large subjects not fitting comfortably into the scanner
    • Difficulty lying supine and still for up to 3 hours in the MRI unit or claustrophobia
  20. Untreated, uncontrolled sleep apnea
  21. Impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
  22. Respiratory: chronic pulmonary disorders e.g. severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, patients with a history of drug allergies, asthma or hay fever, and multiple allergies where the benefit/risk of administering Definity® is considered unfavorable by the study physicians in relation to the product labeling for Definity.
  23. Currently in a clinical trial involving an investigational product or non-approved use of a drug or device.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03322813

United States, Maryland
University of Maryland Medical System Not yet recruiting
Baltimore, Maryland, United States, 21201
Contact: Charlene Aldrich    410-328-5332   
Principal Investigator: Graeme F Woodworth, MD         
Sponsors and Collaborators

Responsible Party: InSightec Identifier: NCT03322813     History of Changes
Other Study ID Numbers: BT004
First Posted: October 26, 2017    Key Record Dates
Last Update Posted: February 22, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No

Keywords provided by InSightec:
Blood Brain Barrier
Blood Brain Barrier Disruption

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue