Trigeminal Neuropathic Pain
Conditions
Keywords
ExAblate, TcMRgFUS, Thalamotomy
Brief summary
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
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.
Interventions
DEVICETranscranial ExAblate
ExAblate Thalamotomy for Chronic Trigeminal Neuropathic Pain
Sham ExAblate Thalamotomy procedure
DEVICECrossover Transcranial Exablate
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.
Sponsors
InSightec
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Device and Procedure Related Complications | At the time of ExAblate Transcranial thalamotomy procedure through 3-months post-thalamotomy | 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. |
| Numeric Pain Rating Scale (NPRS) | Percent Change in NPRS from before treatment to 3 Months following treatment. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Interference Scale 8a v1.0 From the Patient-Reported Outcomes Measurement Information Systems (PROMIS) Pain Inventory | From pre-treatment through 3 months following treatment. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transcranial ExAblate (MRgFUS) Only ExAblate Transcranial MR Guided Focused Ultrasound (MRgFUS)
Transcranial ExAblate: ExAblate Thalamotomy for Chronic Trigeminal Neuropathic Pain | 5 |
| Sham Transcranial ExAblate First, Then Optional Transcranial ExAblate (MRgFUS) ExAblate MRgFUS Sham Procedure
Sham Transcranial ExAblate: Sham ExAblate Thalamotomy procedure
Crossover Transcranial Exablate: 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. | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Main Randomized Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Transcranial ExAblate (MRgFUS) Only | Total | Sham Transcranial ExAblate First, Then Optional Transcranial ExAblate (MRgFUS) |
|---|---|---|---|
| Age, Continuous Age | 64.3 years STANDARD_DEVIATION 8.9 | 62.0 years STANDARD_DEVIATION 8.3 | 59.6 years STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 10 Participants | 5 Participants |
| Region of Enrollment United States | 5 participants | 10 participants | 5 participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 5 / 5 | 5 / 5 | 3 / 3 |
| serious Total, serious adverse events | 0 / 5 | 1 / 5 | 0 / 3 |
Outcome results
Primary
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).
Time frame: Percent Change in NPRS from before treatment to 3 Months following treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial ExAblate (MRgFUS) Only | Numeric Pain Rating Scale (NPRS) | -9.7 Percent change | Standard Deviation 27.4 |
| Sham Transcranial ExAblate First | Numeric Pain Rating Scale (NPRS) | 12.9 Percent change | Standard Deviation 21.7 |
| Optional Crossover Transcranial Exablate (MRgFUS) | Numeric Pain Rating Scale (NPRS) | 4.8 Percent change | Standard Deviation 8.3 |
Primary
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.
Time frame: At the time of ExAblate Transcranial thalamotomy procedure through 3-months post-thalamotomy
Secondary
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.
Time frame: From pre-treatment through 3 months following treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial ExAblate (MRgFUS) Only | Pain Interference Scale 8a v1.0 From the Patient-Reported Outcomes Measurement Information Systems (PROMIS) Pain Inventory | 12.9 Percent Change | Standard Deviation 28.3 |
| Sham Transcranial ExAblate First | Pain Interference Scale 8a v1.0 From the Patient-Reported Outcomes Measurement Information Systems (PROMIS) Pain Inventory | 16.6 Percent Change | Standard Deviation 30.5 |
| Optional Crossover Transcranial Exablate (MRgFUS) | Pain Interference Scale 8a v1.0 From the Patient-Reported Outcomes Measurement Information Systems (PROMIS) Pain Inventory | 54.7 Percent Change | Standard Deviation 40.1 |