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Extracellular Impact of Ultrasound-induced Blood-brain Barrier Disruption

Primary Purpose

Brain Tumor

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Brain Tumor

Eligibility Criteria

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

Inclusion Criteria: Clinical and radiographic evidence suggesting a diagnosis of a diffuse glioma, or a prior diagnosis of a diffuse glioma, which is large enough (≥3cm) for half of the tumor to be targeted by FUS, but small enough for the standard-of-care resection to incorporate some regions of relatively normal brain adjacent to tumor. Planned neurosurgical resection of this suspected or previously diagnosed brain tumor as part of routine clinical care. Provide written informed consent for the current study and the Neuro-Oncology biorepository for archiving of microdialysate and blood samples collected on this protocol. ECOG performance status (PS) 0, 1, or 2. Willing to undergo neurosurgical resection at Mayo Clinic (Rochester, MN). Exclusion Criteria: Patients who are not appropriate surgical candidates due to current or past medical history or uncontrolled concurrent illness which limits safety of or compliance to study proceedings. Vulnerable populations: pregnant or nursing women, prisoners, mentally handicapped. Contraindication to Definity ®. Cardiac disease or coagulative disease (such as cerebral or systemic vasculopathy, abnormal platelets, documented MI within 6 months of enrollment, pacemaker, hemodynamically unstable cardiac arrhythmia, unstable congestive heart failure, or left ventricular ejection fraction <50%), that would preclude the use of Definity ®, FUS-induced BBB disruption, or surgical resection. Any blood-borne infection that may lead to meningitis or brain abscess due to BBB-disruption. Active seizure disorder that is not attributable to the patient's tumor which is not controlled by medication or due to active drug or alcohol disorder which may be worsened by BBB-disruption. Patients for whom the surgeon feels 5-ALA would be required to perform an optimal resection, since 5-ALA will not be permitted for patients participating in this study. Patients who are at risk of FUS-related complications due to potential risks associated with skull anatomy as determined by pre-operative CT assessment, based on skull thickness, curvature, density, or other features that would increase the risk of skull complications with FUS.

Sites / Locations

  • Mayo Clinic MinnesotaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Focused Ultrasound

Arm Description

Subjects with known or suspected glioma (≥3cm) undergoing routine planned neurosurgical resection will undergo a focused ultrasound prior to the surgery with the InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system

Outcomes

Primary Outcome Measures

Adverse events
Number of adverse deemed related to FUS and/or intraoperative microdialysis after the integration of FUS and intraoperative microdialysis into the neurosurgical workflow for tumor resection
Number of microdialysate aliquots
Number of microdialysate aliquots collected containing >10 μL of volume

Secondary Outcome Measures

Full Information

First Posted
January 28, 2023
Last Updated
October 5, 2023
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT05733312
Brief Title
Extracellular Impact of Ultrasound-induced Blood-brain Barrier Disruption
Official Title
Intraoperative Evaluation of Focused Ultrasound-induced Blood-brain Barrier Disruption
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study seeks to determine the impact of focused ultrasound (FUS) on the composition of the tumor extracellular microenvironment. Researchers will evaluate regions that are very abnormal, as well as regions that have less evidence of disease. A sub-portion of each of these areas will be targeted by focused ultrasound. Microdialysis catheters will then be placd into each region that has and has not been exposed to FUS (total of 4 catheters) to determine how FUS impacts the the brain and tumor extracellular metabolome, including concentration of routine drugs systemically administered prior to, and during surgery. Researchers hope that this information will help reveal the relative contribution of blood-derived compounds to the tumor microenvironment. If successful, microdialysis could be leveraged in the future to simultaneously evaluate pharmacokinetic and pharmacodynamic impacts of future candidate therapies, including those delivered with the aid of FUS.
Detailed Description
This protocol performs FUS immediately prior to clinically indicated brain tumor resection. Accordingly, any drugs administered in the context of routine clinical care, such as Ancef, levetiracetam, and mannitol) and imaging agents (gadolinium and iopamidol) clinically available for pre-operative imaging via MRI or CT, respectively, will be quantified in plasma as well as the interstitial fluid of brain tumor and adjacent brain tissue within and outside the volume of FUS treatment. Patients with large (≥3cm) gliomas and no known contraindications to contrast agents or surgery will be recruited to undergo pre-operative Exablate 4000 Type-2 MR-guided FUS prior to intraoperative high molecular weight microdialysis and standard-of-care glioma resection. Intra-operative CT or O-arm will be obtained with contrast to document the location of catheters relative to tumor and region of blood brain barrier disruption following FUS prior to tumor resection.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Focused Ultrasound
Arm Type
Experimental
Arm Description
Subjects with known or suspected glioma (≥3cm) undergoing routine planned neurosurgical resection will undergo a focused ultrasound prior to the surgery with the InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system
Intervention Type
Device
Intervention Name(s)
InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system
Intervention Description
Focused ultrasound which targets energy to a specific area in the brain based on imaging and disrupts the blood brain barrier which keeps certain drugs and other molecules out of the brain.
Primary Outcome Measure Information:
Title
Adverse events
Description
Number of adverse deemed related to FUS and/or intraoperative microdialysis after the integration of FUS and intraoperative microdialysis into the neurosurgical workflow for tumor resection
Time Frame
3 months post-surgery
Title
Number of microdialysate aliquots
Description
Number of microdialysate aliquots collected containing >10 μL of volume
Time Frame
3 months post-surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinical and radiographic evidence suggesting a diagnosis of a diffuse glioma, or a prior diagnosis of a diffuse glioma, which is large enough (≥3cm) for half of the tumor to be targeted by FUS, but small enough for the standard-of-care resection to incorporate some regions of relatively normal brain adjacent to tumor. Planned neurosurgical resection of this suspected or previously diagnosed brain tumor as part of routine clinical care. Provide written informed consent for the current study and the Neuro-Oncology biorepository for archiving of microdialysate and blood samples collected on this protocol. ECOG performance status (PS) 0, 1, or 2. Willing to undergo neurosurgical resection at Mayo Clinic (Rochester, MN). Exclusion Criteria: Patients who are not appropriate surgical candidates due to current or past medical history or uncontrolled concurrent illness which limits safety of or compliance to study proceedings. Vulnerable populations: pregnant or nursing women, prisoners, mentally handicapped. Contraindication to Definity ®. Cardiac disease or coagulative disease (such as cerebral or systemic vasculopathy, abnormal platelets, documented MI within 6 months of enrollment, pacemaker, hemodynamically unstable cardiac arrhythmia, unstable congestive heart failure, or left ventricular ejection fraction <50%), that would preclude the use of Definity ®, FUS-induced BBB disruption, or surgical resection. Any blood-borne infection that may lead to meningitis or brain abscess due to BBB-disruption. Active seizure disorder that is not attributable to the patient's tumor which is not controlled by medication or due to active drug or alcohol disorder which may be worsened by BBB-disruption. Patients for whom the surgeon feels 5-ALA would be required to perform an optimal resection, since 5-ALA will not be permitted for patients participating in this study. Patients who are at risk of FUS-related complications due to potential risks associated with skull anatomy as determined by pre-operative CT assessment, based on skull thickness, curvature, density, or other features that would increase the risk of skull complications with FUS.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Neurologic Surgery Research Team
Phone
507-266-6858
Email
hoplin.matthew@mayo.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terence Burns, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Minnesota
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neurological Surgery Research Team
Phone
507-266-6858

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

Extracellular Impact of Ultrasound-induced Blood-brain Barrier Disruption

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