Treatment of Anxiety Disorders With Trigeminal Nerve Stimulation

Study Overview
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Brief Summary
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Primary objectives: The primary objective is to ascertain if trigeminal nerve stimulation is an effective treatment with high tolerability for patients with panic disorder, generalized anxiety disorder and social anxiety disorder.

Official Title
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Trigeminal Nerve Stimulation in Anxiety Disorders: a Randomized Controlled Trial

Conditions
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Panic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder

Intervention / Treatment
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* Device: Trigeminal nerve stimulation - active
* Device: Trigeminal nerve stimulation - sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet DSM5 criteria for panic disorder, social anxiety disorder or generalized anxiety disorder. Exclusion Criteria: Subjects undergoing cognitive behavioural therapy. Subjects undergoing pharmacological treatment for an anxiety disorder. Subjects undergoing pharmacological treatment with antidepressants or benzodiazepines. Subjects with moderate to severe major depressive disorder based on the PHQ-9 test (score of 15 or above) at baseline. Moderate to high current suicidality or suicide likely in near future or current suicidal behavior disorder. Concurrent diagnosis of OCD, PTSD, bipolar disorder, schizophrenia, schizoaffective disorder, personality disorders, substance use disorders, intellectual disabilities or dementia. Subjects diagnosed with neurological diseases including trigeminal neuralgia. Pregnant or breastfeeding women. Subjects who are experiencing seizures. Individuals with implanted VNS or other electrical devices. Subjects who are already undergoing transcutaneous electrical nerve stimulation. Consumption of cannabis, any cannabis by-products, illicit drugs, or alcohol above 3 drinks per week. Consumption of natural health products that may affect anxiety or depression symptoms.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active stimulation<br>Active or sham TNS treatment will be performed at the patients' home for approximately 8 hours per night 7 days a week for 8 consecutive weeks. Trigeminal nerve stimulation will occur by placement of electrodes (1.25 silver electrodes Bio-Flex BF4, Biotens/Vermed, Buffalo, NY, USA) bilaterally on the V1 branches of the trigeminal nerve (CNV) located on the forehead. Current will be generated from the EMS 7500 stimulator (TENS Products, Inc., Granby, CO) (Class II medical device) and will be set to a level that is clearly perceptible by each patient (i.e. tingling sensation) but not uncomfortable or painful. Current level will be determined for each patient at baseline and will likely be between 4-6 mA. Active stimulation will occur at 120 Hz with a 250 µs pulse width and with a duty cycle of 30 seconds on to 30 seconds off. | Device: Trigeminal nerve stimulation - active<br>* Active trigeminal nerve stimulation<br>|
| Sham Comparator: Sham stimulation<br>Active or sham TNS treatment will be performed at the patients' home for approximately 8 hours per night 7 days a week for 8 consecutive weeks. Sham stimulation will occur by placement of electrodes (1.25 silver electrodes Bio-Flex BF4, Biotens/Vermed, Buffalo, NY, USA) bilaterally on the V1 branches of the trigeminal nerve (CNV) located on the forehead. Current will be generated from the EMS 7500 stimulator (TENS Products, Inc., Granby, CO) (Class II medical device) and will be set to a level that is clearly perceptible by each patient (i.e. tingling sensation) but not uncomfortable or painful. Current level will be determined for each patient at baseline and will likely be between 4-6 mA. Sham stimulation will use the same parameters of active stimulation, but after 60 seconds the stimulator will turn off. | Device: Trigeminal nerve stimulation - sham<br>* Sham trigeminal nerve stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | Treatment response will be defined as a score of 1 or 2 on the Clinical Global Impression - Improvement scale (CGI-I). CGI-I scores range from 0 to 7. Zero corresponds to not assessed. Low scores correspond to improvement, high scores correspond to worsening. | Clinical Global Impression - Improvement scale (CGI-I) will be administered after 8 weeks of treatment. | 
| Remission | Remission will be defined as a score of 1 or 2 on the Clinical Global Impression - Severity scale (CGI-S). CGI-S scores range from 0 to 7. Zero corresponds to not assessed. Low scores correspond to mild and high scores correspond to severe. | Clinical Global Impression - Severity scale (CGI-S) will be administered after 8 weeks of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Generalized anxiety disorder symptoms | Improvement of generalized anxiety disorder symptoms measured with the Generalized Anxiety Disorder 7-item scale (GAD-7). Scores go from 0 (no generalized anxiety symptoms) to 21 (severe generalized anxiety symptoms). | Generalized Anxiety Disorder 7-item scale (GAD-7) will be administered after 8 weeks of treatment. | 
| Social anxiety disorder symptoms | Improvement of social anxiety disorder symptoms measured with the Social Phobia Inventory (SPIN). Scores go from 0 (no social anxiety symptoms) to 68 (severe social anxiety symptoms). | Social Phobia Inventory (SPIN) will be administered after 8 weeks of treatment. | 
| Panic disorder symptoms | Improvement of panic disorder symptoms measured with the Panic Disorder Severity Scale - Self Report version (PDSS-SR). Scores go from 0 (no panic symptoms) to 4 (severe panic symptoms). | Panic Disorder Severity Scale - Self Report version (PDSS-SR) will be administered after 8 weeks of treatment. | 
| Functioning | Improvement of functioning measured with the Sheehan Disability Scale (SDS). Scores go from 0 (no functional impairment) to 10 (severe functional impairment). | Sheehan Disability Scale (SDS) will be administered after 8 weeks of treatment. | 
| Sustained response | Treatment response will be defined as a score of 1 or 2 on the Clinical Global Impression - Improvement scale (CGI-I). CGI-I scores range from 0 to 7. Zero corresponds to not assessed. Low scores correspond to improvement, high scores correspond to worsening. | Clinical Global Impression - Improvement scale (CGI-I) will be administered two weeks after the end of the treatment. | 
| Sustained remission | Remission will be defined as a score of 1 or 2 on the Clinical Global Impression - Severity scale (CGI-S). CGI-S scores range from 0 to 7. Zero corresponds to not assessed. Low scores correspond to mild and high scores correspond to severe. | Clinical Global Impression - Severity scale (CGI-S) will be administered two weeks after the end of the treatment. |