Extracellular Impact of Ultrasound-induced Blood-brain Barrier Disruption

Intraoperative Evaluation of Focused Ultrasound-induced Blood-brain Barrier Disruption

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.

Study Overview

• Status: Recruiting
• Conditions: Brain Tumor
• Intervention / Treatment: Device: InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system

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.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Neurologic Surgery Research Team; Phone Number: 507-266-6858; Email: hoplin.matthew@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Minnesota
      • Contact: Neurologic Surgery Research Team; Phone Number: 507-266-6858; Email: hoplin.matthew@mayo.edu
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Terence C. Burns, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Focused Ultrasound; 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	Device: InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	3 months post-surgery
Number of microdialysate aliquots	Number of microdialysate aliquots collected containing >10 μL of volume	3 months post-surgery

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Terence C. Burns, M.D., Ph.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2024
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2027

Study Registration Dates

• First Submitted: January 28, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Therapeutics; Drug Therapy; Drug Delivery Systems
• Other Study ID Numbers: 22-001933; NCI-2024-03111 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No