Treatment of Anxiety Disorders With Trigeminal Nerve Stimulation

Not Applicable

Active, not recruiting

• Conditions: Panic Disorder; Social Anxiety Disorder; Generalized Anxiety Disorder
• Interventions: Device: Trigeminal nerve stimulation - sham; Device: Trigeminal nerve stimulation - active

• Registration Number: NCT04931134
• Lead Sponsor: Dr. Rafael Freire

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-07
• Study First Submitted QC: 2021-06-11
• Study First Posted: 2021-06-18
• Study Start: 2022-02-07
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-04
• Last Update Posted: 2025-04-08
• Primary Completion: 2025-12-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham stimulation	Trigeminal nerve stimulation - sham	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.
Active stimulation	Trigeminal nerve stimulation - active	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.

Primary Outcome Measures

Name	Time	Method
Remission	Clinical Global Impression - Severity scale (CGI-S) will be administered after 8 weeks of treatment.	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.
Response	Clinical Global Impression - Improvement scale (CGI-I) will be administered after 8 weeks of treatment.	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.

Secondary Outcome Measures

Name	Time	Method
Sustained remission	Clinical Global Impression - Severity scale (CGI-S) will be administered two weeks after the end of the treatment.	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.
Social anxiety disorder symptoms	Social Phobia Inventory (SPIN) will be administered after 8 weeks of treatment.	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).
Panic disorder symptoms	Panic Disorder Severity Scale - Self Report version (PDSS-SR) will be administered after 8 weeks of treatment.	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).
Sustained response	Clinical Global Impression - Improvement scale (CGI-I) will be administered two weeks after the end of the treatment.	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.
Generalized anxiety disorder symptoms	Generalized Anxiety Disorder 7-item scale (GAD-7) will be administered after 8 weeks of treatment.	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).
Functioning	Sheehan Disability Scale (SDS) will be administered after 8 weeks of treatment.	Improvement of functioning measured with the Sheehan Disability Scale (SDS). Scores go from 0 (no functional impairment) to 10 (severe functional impairment).

Trial Locations

Locations (1)

Kingston Health Sciences Centre; 🇨🇦 Kingston, Ontario, Canada