Focused Ultrasound for Low Grade Glioma

Overseen By Barshen Habelhah

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Neurological Associates of West Los Angeles

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 hour

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The limitation of treating intrinsic brain pathologies has been circumvented with neurosurgical techniques; however, less invasive approaches may be desirable particularly for widespread or multifocal disease and when long term and repetitive administration is required. This study seeks to investigate the efficacy of focused ultrasound. Patients with either low grade gliomas or neurodegenerative dementias will be evaluated for study candidacy. There are no immediate benefits for patients who choose to participate; however, the information gained from this study will contribute to the research base and help patients in similar situations in the future.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Focused Ultrasound for Low Grade Glioma?

Research shows that focused ultrasound can temporarily open the blood-brain barrier, allowing chemotherapy drugs to reach brain tumors more effectively. This technique has been shown to be safe and feasible in both animal models and early human studies, enhancing drug delivery to brain tumors. ^{1 2 3 4 5}

Is Focused Ultrasound generally safe for humans?

Focused Ultrasound has been shown to be safe in humans for opening the blood-brain barrier, with studies reporting no adverse clinical or radiologic events related to the procedure. It has been used safely in combination with chemotherapy for brain tumors, demonstrating its potential for safe, targeted drug delivery. ^{1 4 6 7 8}

How does the treatment Focused Ultrasound differ from other treatments for low-grade glioma?

Focused Ultrasound is unique because it can noninvasively open the blood-brain barrier (a protective layer around the brain) to allow better delivery of drugs to the tumor. This approach is different from traditional methods, which often struggle to get medications past this barrier. ^{4 9 10 11 12}

Research Team

Sheldon Jordan, M.D.

Principal Investigator

Neurologist, NAOWLA

Eligibility Criteria

This trial is for adults over 18 with low grade gliomas who are already getting regular MRI scans. It's not for those with cognitive decline from mild to moderate dementia.

Inclusion Criteria

I regularly get MRI scans to monitor my low grade brain tumor.

Exclusion Criteria

I have mild to moderate memory or thinking problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo focused ultrasound treatment to evaluate the permeability of the blood-brain barrier

1 hour

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse event reporting and fMRI scans

24 hours

1 visit (in-person)

Treatment Details

Interventions

• Focused Ultrasound

Trial Overview The study tests the use of focused ultrasound on the brain. The goal is to see if it can safely make the blood-brain barrier more permeable, potentially helping treat brain conditions less invasively.

Participant Groups

Group I: Focused Ultrasound Experimental Treatment 1 Intervention

The ultrasound treatment will last either 1 hour or 20 minutes total time for the DWL device or Brainsonix Focused Ultrasound Device, respectively.

Focused Ultrasound is already approved in United States, European Union for the following indications:

Approved in United States as Gemzar for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Ovarian cancer
• Pancreatic cancer

Approved in European Union as Gemzar for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Ovarian cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Neurological Associates of West Los Angeles

Lead Sponsor

Trials

26

Recruited

4,000+

Findings from Research

In a phase I study involving 5 patients with high-grade glioma, MR-guided focused ultrasound (MRgFUS) was successfully used to temporarily open the blood-brain barrier (BBB) without surgery, allowing for enhanced delivery of chemotherapy.

The procedure was safe and well-tolerated, showing no adverse effects, and resulted in a significant increase in chemotherapy delivery to the targeted brain tissue, indicating its potential for improving treatment efficacy in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. Mainprize, T., Lipsman, N., Huang, Y., et al.[2020]

Diffuse Midline Glioma (DMG), previously known as Diffuse Intrinsic Pontine Glioma (DIPG), is a challenging pediatric brain tumor with no curative treatments available despite over 250 clinical trials.

Focused Ultrasound (FUS) is a promising noninvasive technology that can temporarily disrupt the blood-brain barrier, potentially allowing for better delivery of therapies and enhancing the effectiveness of treatments like chemotherapy and radiation for DMG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past, present and future of Focused Ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting. Parekh, K., LeBlang, S., Nazarian, J., et al.[2023]

Transcranial microbubble-enhanced focused ultrasound (MB-FUS) safely and effectively opens the blood-brain barrier (BBB) in patients with infiltrating gliomas, as demonstrated in a Phase 0 clinical trial with MRI and histopathology confirming reproducible results.

The study found a significant increase in drug accumulation in treated tumor tissues, with a 2.2-fold increase in fluorescein compared to untreated areas, suggesting that MB-FUS could enhance the delivery of therapeutics for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound. Anastasiadis, P., Gandhi, D., Guo, Y., et al.[2022]

Low-intensity MR-guided focused ultrasound combined with microbubbles shows promise for safely delivering drugs to the central nervous system by temporarily opening the blood-brain barrier, which is crucial for treating brain cancers.

Preclinical studies have demonstrated the safety and preliminary efficacy of this method in animal models, suggesting it could be a noninvasive and repeatable approach for targeting drug delivery in neuro-oncology patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases. Meng, Y., Suppiah, S., Surendrakumar, S., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Focused ultrasound mediated blood-brain barrier opening is safe and feasible in a murine pontine glioma model. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Past, present and future of Focused Ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in Focused Ultrasound for the Treatment of Brain Tumors. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Blood-brain barrier disruption and delivery of irinotecan in a rat model using a clinical transcranial MRI-guided focused ultrasound system. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases. [2020]

9. Austria pubmed.ncbi.nlm.nih.gov

Linear array ultrasound in low-grade glioma surgery: histology-based assessment of accuracy in comparison to conventional intraoperative ultrasound and intraoperative MRI. [2018]

10. Scotland pubmed.ncbi.nlm.nih.gov

Two-dimensional high-end ultrasound imaging compared to intraoperative MRI during resection of low-grade gliomas. [2016]

11. United States pubmed.ncbi.nlm.nih.gov

A comparison between preoperative magnetic resonance and intraoperative ultrasound tumor volumes and margins. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Pattern of use of intraoperative ultrasound in surgery for brain tumors influences outcomes in glial tumors. [2022]