Focused Ultrasound for Trigeminal Neuralgia

Overseen By Ranyah Almardawi, MBBS/MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Maryland, Baltimore

Must be taking: Anticonvulsants

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Severe psychiatric disorder, Pregnancy, Unstable cardiac status, Severe hypertension, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method using MRI-guided focused ultrasound (ExAblate Transcranial treatment) to treat Trigeminal Neuralgia, a severe and potentially disabling facial pain. The treatment targets a small area in the brain with ultrasound to reduce pain. This trial may suit individuals who have experienced chronic, severe facial pain for over six months without relief from standard treatments. As an unphased trial, it provides a unique opportunity for patients to explore innovative treatment options not yet widely available.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, you cannot participate if you are on anticoagulant or antiplatelet medications.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, if you are taking anticoagulant or antiplatelet medications, you may not be eligible to participate.

What prior data suggests that this MRI-guided focused ultrasound is safe for treating Trigeminal Neuralgia?

Research has shown that the ExAblate Transcranial treatment, which uses focused ultrasound to target specific brain areas, is generally safe. In various studies, patients tolerated this treatment well. It is minimally invasive, meaning it doesn't involve surgery, often resulting in fewer complications.

Previous studies found that some patients may experience mild side effects like headaches or dizziness after treatment, but these usually don't last long. Importantly, more serious side effects are rare. The treatment focuses ultrasound energy precisely, reducing the risk of harming nearby brain tissue.

While researchers are still studying this treatment for trigeminal neuralgia (a type of severe facial pain), it has been used safely for other conditions. This suggests it could be a promising option for those seeking new ways to manage their pain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for trigeminal neuralgia, like medications or invasive surgeries, focus on managing symptoms or physically altering nerve structures. But the ExAblate Transcranial treatment works differently, targeting a specific brain area called the central lateral thalamic nucleus using focused ultrasound. This non-invasive approach offers the potential to relieve pain by precisely destroying problematic cells without the need for incisions or long recovery times. Researchers are excited about this method because it could offer a safer, quicker, and less invasive alternative to existing options.

What evidence suggests that the ExAblate Transcranial treatment is effective for Trigeminal Neuralgia?

Research has shown that MRI-guided focused ultrasound (MRgFUS), administered in this trial as the ExAblate Transcranial treatment, might help treat trigeminal neuralgia, a type of severe facial pain. This treatment uses ultrasound energy to target and destroy small groups of cells believed to cause the pain, focusing on a specific area in the brain called the central lateral thalamic nucleus. Early results suggest this method could manage pain without requiring surgery. Studies indicate that this approach is safe and offers hope for people with chronic pain conditions. ^{2 3 4 6 7}

Who Is on the Research Team?

Dheeraj Gandhi, MD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for adults aged 21-75 with chronic, severe facial pain from Trigeminal Neuralgia that hasn't improved after standard treatments including anticonvulsants and possibly surgery. Candidates must be able to give consent, attend all visits, communicate during treatment, and have a feasible central lateral thalamotomy based on imaging.

Inclusion Criteria

Subjects who are able and willing to give consent and able to attend all study visits

I am between 22 and 74 years old.

Two members of the medical team have agreed upon inclusion and exclusion criteria

Exclusion Criteria

You are expected to live for less than a year.

Your skull density ratio is lower than 0.4 plus or minus 0.05.

Inability to provide informed consent, for example due to underlying cognitive impairment or aphasia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the ExAblate Transcranial focused ultrasound treatment targeting the central lateral thalamic nucleus

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Multiple visits (in-person and/or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• ExAblate Transcranial treatment

Trial Overview The study tests the safety and effectiveness of MRI-guided focused ultrasound (MRgFUS) in treating Trigeminal Neuralgia. This non-invasive technique uses sound waves directed at the brain area responsible for the pain under MRI guidance.

How Is the Trial Designed?

Group I: ExAblate Transcranial treatment Experimental Treatment 1 Intervention

The ExAblate Transcranial system will be used to destroy a small cluster of cells that may be causing the study participant's pain . The ExAblate uses ultrasound to heat a small spot in the brain called central lateral thalamic nucleus. Ultrasound passes through the skin and skull and into the brain to focus on this particular spot.

ExAblate Transcranial treatment is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as ExAblate Neuro for:

• Essential Tremors
• Tremor Dominant Idiopathic Parkinson’s Disease
• Neuropathic Pain
• Metastatic Bone Cancer
• Uterine Fibroids

Approved in United States as ExAblate Neuro for:

• Medication-refractory Essential Tremor
• Tremor Dominant Parkinson Disease
• Advanced Parkinson Disease
• Pain Palliation of Metastatic Bone Cancer
• Ablation of Uterine Fibroid Tissue

Approved in Canada as ExAblate Neuro for:

• Pain Palliation of Metastatic Bone Cancer
• Treatment of Uterine Fibroids

Approved in Japan as ExAblate Neuro for:

• Pain Palliation of Metastatic Bone Cancer
• Treatment of Uterine Fibroids

Approved in China as ExAblate Neuro for:

• Pain Palliation of Metastatic Bone Cancer
• Treatment of Uterine Fibroids

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

InSightec

Industry Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Focused Ultrasound Foundation

Collaborator

Trials

18

Recruited

460+

Published Research Related to This Trial

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has the potential to provide a non-invasive treatment for primary trigeminal neuralgia, which is known for causing severe pain and significantly impacting quality of life.

The effectiveness of MR-HIFU relies on precise targeting, careful temperature monitoring to protect surrounding tissues, and optimal radiation doses, suggesting that with the right conditions, it could be a safer alternative to current treatments that have high recurrence rates and complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The applicability and efficacy of magnetic resonance-guided high intensity focused ultrasound system in the treatment of primary trigeminal neuralgia. Ma, Y., Hsu, G., Zhang, F.[2021]

A 63-year-old patient with a recurrent glioblastoma underwent transcranial MR-guided focused ultrasound surgery (MRgFUS), demonstrating the feasibility of this noninvasive technique for brain tumor ablation.

The procedure involved 25 high-power sonications and successfully achieved partial tumor ablation without causing neurological deficits or adverse effects, highlighting its safety and potential for treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. Coluccia, D., Fandino, J., Schwyzer, L., et al.[2020]

The first clinical experience with MRgFUS using the ExAblate 2100 system for non-invasive breast cancer showed promising results, with no severe adverse events reported in two patients.

Pathological examinations indicated that the treatment effectively induced tumor necrosis, suggesting that MRgFUS is a safe and feasible option for non-invasive breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative use of magnetic resonance imaging-guided focused ultrasound surgery for non-invasive breast cancer: a report of two cases. Matsutani, A., Ide, Y., Miura, S., et al.[2020]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique that can precisely target and treat brain disorders by creating thermal lesions and disrupting the blood-brain barrier, which is a significant advancement in neurotherapeutics.

MRgFUS has been successfully used in various clinical applications, including treating bone metastases and uterine fibroids, and is being explored as a safer alternative to traditional neurosurgery for a range of brain-related conditions, supported by studies from small animal models to large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

Transcranial magnetic resonance-guided high-intensity focused ultrasound (tcMRgHIFU) was successfully used to treat nine patients with chronic neuropathic pain through precise thermal ablations, demonstrating its potential as a noninvasive treatment for brain diseases.

The procedure was well tolerated by all patients, with no reported side effects or neurological deficits, highlighting the safety and reliability of tcMRgHIFU for neurosurgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity focused ultrasound for noninvasive functional neurosurgery. Martin, E., Jeanmonod, D., Morel, A., et al.[2011]

In a study involving 12 patients with chronic neuropathic pain, transcranial magnetic resonance imaging-guided focused ultrasound (tcMRgFUS) achieved significant pain relief, with a mean reduction of 49% at 3 months and 57% at 1 year after treatment.

The tcMRgFUS technique demonstrated high targeting precision and safety, with only one complication reported, and it offers a noninvasive alternative to traditional neurosurgery, minimizing risks such as infection and mechanical brain tissue damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Jeanmonod, D., Werner, B., Morel, A., et al.[2022]

Modern transcranial magnetic resonance-guided focused ultrasound is a non-invasive treatment that effectively targets and destroys specific areas of brain tissue, making it a promising option for various neurological disorders.

This technique uses real-time MR thermography to ensure safety by monitoring tissue temperatures, allowing for precise ablation without damaging surrounding brain structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Frequency Ultrasound Ablation in Neurosurgery. Pomeraniec, J., Elias, WJ., Moosa, S.[2023]

Transcranial MR-guided focused ultrasound surgery (MRgFUS) successfully targeted the trigeminal nerve in a cadaveric model, achieving focal heating of up to 18°C without significant collateral damage to surrounding structures.

The study demonstrated that using no-pass regions through the petrous bone significantly reduced unwanted heating in adjacent areas, suggesting a promising approach for safe and effective treatment of trigeminal nerve conditions, although further in vivo studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic resonance-guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study. Monteith, SJ., Medel, R., Kassell, NF., et al.[2016]

Citations

1. thejns.org thejns.org/view/journals/j-neurosurg/118/2/article-p319.xml

Transcranial magnetic resonance–guided focused ultrasound ... With the ExAblate Neuro (InSightec), 1024 ultrasound transducers transmit ultrasound energy through the skull that converges onto a focal spot ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4687492/

Transcranial MR-Guided Focused Ultrasound - PubMed Central MR guided focused ultrasound is a new, minimally invasive method of targeted tissue thermal ablation that may be of use to treat central neuropathic pain, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03309813

NCT03309813 | Feasibility Study of ExAblate Thalamotomy ... This study is to show that for patients with treatment-refractory chronic trigeminal neuropathic pain, ExAblate Neuro focused ultrasound (FUS) can safely ...

4. fusfoundation.org fusfoundation.org/for-researchers-and-clinicians/foundation-funded-research-projects/

Foundation Funded Research Projects A Feasibility Study to Evaluate Safety and Initial Effectiveness of ExAblate Transcranial MR Guided Focused Ultrasound for Unilateral Thalamotomy in the ...

5. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150038B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The treatment effect of the ExAblate Neuro is achieved by guiding the focus of the ultrasound energy to the target region. The energy is then ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04579692

NCT04579692 | MR Guided Focused Ultrasound (FUS) for ... The purpose of this study is to assess the safety and effectiveness of MRI-guided focused ultrasound (MRgFUS) for treating Trigeminal Neuralgia.

7. ajnr.org ajnr.org/content/ajnr/early/2023/12/14/ajnr.A8038.full.pdf

A Review Guided Focused Ultrasound − Imaging MR ... The Insightec ExAblate Neuro system can be used with 2 different frequency transducers, referred to colloquially as high-intensity focused ...