Feasibility Study of ExAblate Thalamotomy for Treatment of Chronic Trigeminal Neuropathic Pain

Study Overview
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Brief Summary
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The goal of this prospective, randomized, sham-controlled, crossover study is to evaluate the safety and feasibility of ExAblate Neuro treatment of chronic trigeminal neuropathic pain.

Detailed Description
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This study is to show that for patients with treatment-refractory chronic trigeminal neuropathic pain, ExAblate Neuro focused ultrasound (FUS) can safely create lesions bilaterally in the thalamic nuclei to reduce pain and provide functional benefits in daily activities. After informed consent and screening, eligible subjects will be randomized to either an ExAblate treatment or a Sham Control procedure. Subjects who are randomized to Sham Control will undergo the same procedure and follow-up visits through their Month 3 visit. After the Month 3 assessments are complete, all subjects will be un-blinded and those in the Sham treated group will have the option for an actual ExAblate treatment in an un-blinded fashion, as long as they still qualify for ExAblate treatment.

Official Title
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A Feasibility Study of Focused Ultrasound to Perform Bilateral Medial Thalamotomy for the Treatment of Chronic Trigeminal Neuropathic Pain

Conditions
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Trigeminal Neuropathic Pain

Intervention / Treatment
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* Device: Transcranial ExAblate
* Device: Sham Transcranial ExAblate
* Device: Crossover Transcranial Exablate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, between 18 and 75 years, inclusive Subjects who are able and willing to give consent and able to attend all study visits Severe chronic, trigeminal neuropathic pain of ≥6 months duration. Pain is medication-refractory to adequate trials of at least 3 prescription medications commonly used for symptomatic relief of neuropathic pain with current adjunctive use of at least one medication. An adequate medication trial is defined as a therapeutic dose of each medication without sufficient effect. Pain is treatment-resistant to at least one interventional therapies including injections, procedures, neuromodulation, and surgery. Able to communicate sensations during the focused ultrasound treatment Stable prescribed doses of all symptomatic pain medications for 30 days prior to study entry and for the duration of the 3-month blinded phase of the study. Exclusion Criteria: Craniofacial pain syndromes related to malignancy of the head and neck Idiopathic trigeminal neuralgia Headache syndromes like migraine, cluster headache Temporomandibular joint syndrome Atypical facial pain or pain related to a somatoform disorder Subjects with active psychiatric illness will be excluded. For the purpose of this study, active psychiatric illness includes: Exhibiting current suicide ideation and/or a history of suicide attempt within past 2 years been hospitalized for the treatment of a psychiatric illness within the past 2 years received transcranial magnetic stimulation for depression treatment received electroconvulsive therapy for depression Any presence or history of psychosis will be excluded. Subjects with unstable cardiac status including: Unstable angina pectoris on medication Subjects with documented myocardial infarction within six months of protocol entry Significant congestive heart failure defined with ejection fraction < 40 Subjects with unstable ventricular arrhythmias Subjects with atrial arrhythmias that are not rate-controlled Severe hypertension (diastolic BP > 100 on medication) Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (can be up to 4 hours of total table time.) Subjects participating or have participated in another clinical trial in the last 30 days Presence of systemic neurological disease or dysfunction Known life-threatening systemic disease Subjects with brain tumors or any significant intracranial mass. Trigeminal or cavernous sinus tumors causing neuropathic pain are not excluded. Pregnancy or lactation Legal incapacity or limited legal capacity Subjects with a deep brain stimulation implant or with a prior stereotactic thalamic ablation History of hemorrhagic stroke or cerebrovascular event within the past year of treatment exhibiting incomplete resolution History of seizures within past year of treatment Severe kidney disease or on dialysis Subjects who are unable to tolerate medications due to intolerable side effects. Subjects with pain other than craniofacial neuropathic pain.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Subjects were randomized to an Exablate Test Arm or a Sham Control Arm. After completing the Month 3 Sham study visit, Sham Controls could elect to receive the actual Exablate ablation (same as test arm) and continue follow-up in a Crossover Arm.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial ExAblate<br>ExAblate Transcranial MR Guided Focused Ultrasound (MRgFUS) | Device: Transcranial ExAblate<br>* ExAblate Thalamotomy for Chronic Trigeminal Neuropathic Pain<br>* Other names: Thalamotomy;|
| Sham Comparator: Sham Transcranial ExAblate<br>ExAblate MRgFUS Sham Procedure | Device: Sham Transcranial ExAblate<br>* Sham ExAblate Thalamotomy procedure<br>Device: Crossover Transcranial Exablate<br>* Subjects randomized to the Sham Exablate could opt for the Crossovover Transcranial Exablate Arm (Exablate Thalamotomy) after completing the Month 3 visit in the Sham Arm.<br>* Other names: Thalamotomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of Device and Procedure Related Complications | To evaluate the incidence and severity of adverse events associated with ExAblate lesioning of the bilateral medial thalamus for painful neuropathies of the face and head that are severe and treatment-refractory. | At the time of ExAblate Transcranial thalamotomy procedure through 3-months post-thalamotomy | 
| Numeric Pain Rating Scale (NPRS) | Numeric Pain Rating Scale (NPRS) change in worst pain experienced over 24 hours before and at 3 months following bilateral FUS medial thalamotomy versus sham procedures was determined from the 11-point numeric pain rating scale with 0 as no pain and 10 the worst pain imaginable. High NPRS scores are worse pain (0 is no pain, 10 is maximum). Percent change from Baseline at Month 3 was calculated as follows: 100*(NPRS Score at Baseline - NPRS Score at Month 3)/NPRS Score at Baseline. High percent change in NPRS Score from Baseline is better (improved pain). | Percent Change in NPRS from before treatment to 3 Months following treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Interference Scale 8a v1.0 From the Patient-Reported Outcomes Measurement Information Systems (PROMIS) Pain Inventory | The Pain Interference 8a v1.0 Scale (Short Form) from the Patient-Reported Outcomes Measurement Information Systems (PROMIS) Pain Inventory is an 8-item patient completed short form with each item on a 5-point scale (0-4). The total score possible ranges from 0-32. The PROMIS pain interference scale measures the degree to which pain interferes with activities of daily living. A high percent change from Baseline at 3 Months post-treatment is better, shows improvement. | From pre-treatment through 3 months following treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ExAblate, TcMRgFUS, Thalamotomy