Trigeminal Nerve Stimulation in Treatment-resistant Generalized Anxiety Disorder: a Feasibility Study

Not Applicable

Recruiting

• Conditions: Generalized Anxiety Disorder

• Registration Number: NCT06278909
• Lead Sponsor: Dr. Rafael Freire

Brief Summary

This is a feasibility study for trigeminal nerve stimulation (TNS) in patients with treatment-resistant generalized anxiety disorder (TR-GAD). Ten participants will receive TNS for 8 weeks as an augmentation strategy to pharmacological treatment for generalized anxiety disorder (GAD).

* The primary objective is to ascertain if TNS is a safe and well-tolerated treatment for patients with TR-GAD.

* The secondary objective will be to monitor changes in GAD symptom severity throughout the study.

Results from this study will inform a randomized controlled trial to be conducted in the future.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-01-18
• Study First Submitted: 2024-02-09
• Study First Submitted QC: 2024-02-23
• Study First Posted: 2024-02-26
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-04
• Last Update Posted: 2025-04-08
• Primary Completion: 2026-03-01
• Study Completion: 2026-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5) criteria for generalized anxiety disorder.
• Subjects on a stable dose of an selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) for at least 8 weeks.
• Treatment-resistant - treatment resistance will be defined as lack of response to at least two drugs, from two different classes of drugs considered first-line or second-line for GAD. Only trials lasting at least 8 weeks, and with at least the minimum effective dose of the given medication will be considered failed trials.

Exclusion Criteria

• Moderate to severe major depressive disorder
• Moderate to high suicidality
• Diagnosis of obsessive compulsive disorder (OCD), PTSD, bipolar disorder, schizophrenia, schizoaffective disorder, personality disorders, substance use disorders, intellectual disabilities and dementia or other neurological diseases including trigeminal neuralgia
• Pregnant or breastfeeding women
• Participants who are experiencing seizures
• Implanted vagal nerve stimulation (VNS) or other electrical devices
• Participants 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: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent side effects measured with the NSEC	Baseline visit, 4-week visit and 8-week visit.	Monitor participants for minor treatment-emergent side effects measured with the Neurostimulation Side-Effect Checklist (NSEC).; NSEC is a list of 31 possible side effects from neurostimulation or from antidepressants. Each item is rated from 0 (absent) to 3 (severe).
Incidence of treatment-emergent adverse events	Throughout the study, 8 weeks	Monitor participants for treatment-emergent adverse events and serious adverse events.
Response to treatment defined by CGI-I score below 3	4-week visit and 8-week visit.	Response to treatment, which will be defined as a score of 1 or 2 on the Clinical Global Impression - Improvement (CGI-I) scale.; CGI-I is a clinician administered one-item clinical scale rated from 1 (very much improved) to 7 (very much worse). Not assessed would confer score 0.

Secondary Outcome Measures

Name	Time	Method
Change in anxiety severity measured by CGI-S	Baseline visit, 4-week visit and 8-week visit.	Changes in scores for CGI-S by comparing the scores in each visit. CGI-S is a clinician administered one-item clinical scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Not assessed would confer score 0.
Remission defined by CGI-S score below 3	4-week visit and 8-week visit.	Remission will be defined as a score of 1 or 2 on the Clinical Global Impression - Severity (CGI-S) scale.; CGI-S is a clinician administered one-item clinical scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Not assessed would confer score 0.
Change of anxiety symptoms measured with GAD-7	Baseline visit, 4-week visit and 8-week visit.	Changes in scores for Generalized Anxiety Disorder 7-item scale (GAD-7) by comparing the scores in each visit.; GAD-7 is a self-rated 7-item scale, each item is rated from 0 (not at all) to 3 (nearly every day).
Change of anxiety symptoms measured with BAI	Baseline visit, 4-week visit and 8-week visit.	Changes in scores for Beck Anxiety Inventory (BAI) by comparing the scores in each visit.; BAI is a self-rated 21-item scale, each item is rated from 0 (not at all) to 3 (severely - it bothered me a lot).
Change of anxiety symptoms measured with PSWQ	Baseline visit, 4-week visit and 8-week visit.	Changes in scores for Penn State Worry Questionnaire (PSWQ) by comparing the scores in each visit.; PSWQ is a self-rated 16-item scale, each item is rated from 1 (not at all typical of me) to 5 (very typical of me).

Trial Locations

Locations (1)

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