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

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.

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.