Treatment of Anxiety Disorders With Trigeminal Nerve Stimulation

Trigeminal Nerve Stimulation in Anxiety Disorders: a Randomized Controlled Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Generalized Anxiety Disorder; Social Anxiety Disorder; Panic Disorder
• Intervention / Treatment: Device: Trigeminal nerve stimulation - active; Device: Trigeminal nerve stimulation - sham

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yan Deng; Phone Number: +1 613-548-3232; Email: yan.deng@queensu.ca

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada
      • Kingston Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active stimulation; 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; Active trigeminal nerve stimulation
Sham Comparator: Sham stimulation; 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; Sham trigeminal nerve stimulation

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Dr. Rafael Freire
• Investigators: Principal Investigator: Rafael Freire, MD PhD, Department of Psychiatry, Queen's University

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 11, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Phobic Disorders; Anxiety Disorders; Phobia, Social; Panic Disorder
• Other Study ID Numbers: 6028648

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes