Paresthesia-free Peripheral Nerve Field Stimulation for Trigeminal Neuralgia (FreeST Trial)

Study Overview
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Brief Summary
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Study type: Prospective, double-blinded, double arm, cross-over, randomized controlled clinical trial. Brief protocol: Postoperative week 0-2 -> Conventional parameters (parameters tested during trial period) Postoperative week 2-6 -> Sham stimulation (2 weeks) and paresthesia-free stimulation (2 weeks) double-blind crossover design Postoperative week 6 - month 12 -> Parameters that patients feel more benefit from

Detailed Description
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Background: Peripheral Nerve Field Stimulation (PNFS) has been utilized for the treatment of facial pain for around 60 years, and the commercial devices needed to deliver PNFS have been available for around 30 years. The safety and efficacy of the procedure has been demonstrated by various uncontrolled observational studies. It serves as a part of daily neurosurgical practice for selected patients in UHN Toronto Western Hospital. This therapeutic modality involves subcutaneous implantation of electrodes in the vicinity of trigeminal nerve branches and application of electrical current using a permanently implanted pulse generator (IPG). Similar to other forms of neuromodulation, PNFS is non-ablative, reversible, adjustable and associated with a relatively low risk of severe complications. A meta-analysis of paresthesia-inducing (PI) PFNS studies in the literature revealed a treatment efficacy of 75% decrease in VAS scores (mean difference: -6.32 out of 10) with PNFS utilization for facial pain. (PMID: 35180702) Study design: Patients who underwent a successful unilateral PNFS implantation surgery (trial and permanent implantation) for a facial pain syndrome as a standard of care treatment, will be screened for inclusion after permanent implantable pulse generator (IPG) implantation. Upon consent, the investigators will set up participants' IPG to deliver stimulation with parameters tested during the trial period (paresthesia-inducing parameters) for 2 weeks. The participants will come back to hospital at postoperative week 2 and will be randomized (1:1 ratio) between the two arms of the study (Group 1= sham, Group 2= paresthesia-free (PF) stimulation). Each participant will consecutively experience all two stimulation groups by 2-week periods in a crossover design. Both participants and clinical investigators that will assess the pain will be blind during the study period (between postoperative week 2 and 6). After 6 weeks, the treatment arms will be merged and all the participants will receive any stimulation parameter that they feel more benefit from (best parameter). Outcomes will be assessed 6 and 12 months post-operatively.

Official Title
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Paresthesia-free Peripheral Nerve Field Stimulation for Trigeminal Neuralgia: a Double-blinded, Randomized Trial (FreeST Trial)

Conditions
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Trigeminal Neuralgia, Facial Pain

Intervention / Treatment
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* Other: Paresthesia-free Peripheral Nerve Field Stimulation
* Other: Sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of a medically-refractory unilateral facial pain syndrome as defined by the Burchiel classification but excluding atypical facial pain (somatoform pain disorder) Recent successful PNFS trial and permanent implantation surgery Average preoperative episodic/constant pain intensity of 5 or greater out of 10 cm on the VAS Capable of providing informed consent and complying with study procedures Patients may or may not use a pain medication at the time of recruitment. Medications allowed during the study are long-acting/modulatory analgesics (anticonvulsants such as carbamezapine, oxcarbazepine, pregabalin, gabapentin, lamotrigine; baclofen, botox injections) and short-acting analgesics (non-steroid anti-inflammatory drugs, short-acting opioids, lidocaine or sumatriptan injections) Exclusion Criteria: Currently in a clinical trial involving an investigational product or non-approved use of a drug or device. Active psychiatric disorder or other known condition that can significantly impact pain perception Patients with a revision surgery of a PNFS system by any reason (history of trigeminal pain surgery of other types (i.e., microvascular decompression, gamma knife, percutaneous rhizotomies) are not exclusion criteria) Pregnant and lactating women

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paresthesia-Free Stimulation<br>Duration: 2 weeks | Other: Paresthesia-free Peripheral Nerve Field Stimulation<br>* High frequency and sub-paresthesia threshold intensity parameters will be used for paresthesia-free stimulation of trigeminal nerve branches.<br>|
| Sham Comparator: Sham Stimulation<br>Duration: 2 weeks | Other: Sham stimulation<br>* Stimulation will be turned off.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale (VAS) Score Change | VAS score change between sham condition (postop week 2-4 or postop week 4-6) and Paresthesia-free stimulation condition (postop week 2-4 or postop week 4-6) VAS score ranges from 0 to 100 mm (or 0 to 10 cm). Higher score is worse outcome. | Postoperative week 2 to week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale (VAS) Score Change | Score changes between sham condition (postop week 2-4 or postop week 4-6), Paresthesia-free stimulation condition (postop week 2-4 or postop week 4-6) and Paresthesia-inducing stimulation condition (postop week 0-2) Non-independent within-group comparison VAS score ranges from 0 to 100 mm (or 0 to 10 cm). Higher score is worse outcome. | Postoperative week 0 to week 6 | 
| Barrow Neurological Institute (BNI) pain intensity score change | Score changes between sham condition (postop week 2-4 or postop week 4-6), Paresthesia-free stimulation condition (postop week 2-4 or postop week 4-6) and Paresthesia-inducing stimulation condition (postop week 0-2) Non-independent within-group comparison BNI score ranges from 1 to 5. Higher score is worse outcome. | Postoperative week 0 to week 6 | 
| Brief Pain Inventory (BPI) score change | Score changes between sham condition (postop week 2-4 or postop week 4-6), Paresthesia-free stimulation condition (postop week 2-4 or postop week 4-6) and Paresthesia-inducing stimulation condition (postop week 0-2) Non-independent within-group comparison BPI-Pain Severity Score and BPI-Pain Interference Score range from 0 to 10. Higher score is worse outcome. | Postoperative week 0 to week 6 | 
| Clinician and Patient Global Impression of Change Scale and Patient satisfaction scale score change | Score changes between sham condition (postop week 2-4 or postop week 4-6), Paresthesia-free stimulation condition (postop week 2-4 or postop week 4-6) and Paresthesia-inducing stimulation condition (postop week 0-2) Non-independent within-group comparison Clinician and Patient Global Impression of Change Scale (range from 1 to 7) and Patient satisfaction scale (range from 1 to 5). Higher score is worse outcome. | Postoperative week 0 to week 6 | 
| Adverse effect Profile | Adverse effect Profile | Postoperative week 0 to month 12 | 
| Ratio of patients who chose paresthesia-free or paresthesia-inducing stimulation at week 6, month 6 and 12 | paresthesia-free or paresthesia-inducing stimulation | Postoperative week 6, month 6 and 12 | 
| fMRI BOLD signal change | IPG ON>OFF BOLD signal change (both paresthesia-free and Paresthesia-inducing conditions will be tested) | Between postoperative month 6 and 12 | 
| Visual Analogue Scale (VAS) Score Change | Score changes between baseline and postoperative 6 and 12 months VAS score ranges from 0 to 100 mm (or 0 to 10 cm). Higher score is worse outcome. | Postoperative month 6 and 12 | 
| Barrow Neurological Institute (BNI) pain intensity score change | Score changes between baseline and postoperative 6 and 12 months BNI score ranges from 1 to 5. Higher score is worse outcome. | Postoperative month 6 and 12 | 
| Brief Pain Inventory (BPI) score change | Score changes between baseline and postoperative 6 and 12 months BPI-Pain Severity Score and BPI-Pain Interference Score range from 0 to 10. Higher score is worse outcome. | Postoperative month 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Nerve Field Stimulation