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

Generalized Anxiety Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06278909
• Other study ID #: 6036699
• Status: Recruiting
• Phase: N/A
• Start date: January 18, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: Queen's University
• Contact: Yan Deng
• Phone: +1 613-548-7839
• Email: yan.deng[@]queensu.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 30, 2025
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Anxiety Disorders
• Generalized Anxiety Disorder

Intervention

Device:
• Trigeminal Nerve Stimulation
Active trigeminal nerve stimulation

Locations

Country	Name	City	State
Canada	Kingston Health Sciences Centre	Kingston	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Rafael Freire

Country where clinical trial is conducted

Canada, 

References & Publications (4)

Cook IA, Abrams M, Leuchter AF. Trigeminal Nerve Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder. Neuromodulation. 2016 Apr;19(3):299-305. doi: 10.1111/ner.12399. Epub 2016 Jan 28. — View Citation

Cook IA, Schrader LM, Degiorgio CM, Miller PR, Maremont ER, Leuchter AF. Trigeminal nerve stimulation in major depressive disorder: acute outcomes in an open pilot study. Epilepsy Behav. 2013 Aug;28(2):221-6. doi: 10.1016/j.yebeh.2013.05.008. Epub 2013 Jun 14. — View Citation

Freire RC, Cabrera-Abreu C, Milev R. Neurostimulation in Anxiety Disorders, Post-traumatic Stress Disorder, and Obsessive-Compulsive Disorder. Adv Exp Med Biol. 2020;1191:331-346. doi: 10.1007/978-981-32-9705-0_18. — View Citation

Trevizol AP, Shiozawa P, Sato IA, Calfat EL, Alberto RL, Cook IA, Medeiros HH, Cordeiro Q. Trigeminal Nerve Stimulation (TNS) for Generalized Anxiety Disorder: A Case Study. Brain Stimul. 2015 May-Jun;8(3):659-60. doi: 10.1016/j.brs.2014.12.009. Epub 2014 Dec 31. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events	Monitor participants for treatment-emergent adverse events and serious adverse events.	Throughout the study, 8 weeks
Primary	Incidence of treatment-emergent side effects measured with the NSEC	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).	Baseline visit, 4-week visit and 8-week visit.
Primary	Response to treatment defined by CGI-I score below 3	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.	4-week visit and 8-week visit.
Secondary	Remission defined by CGI-S score below 3	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.	4-week visit and 8-week visit.
Secondary	Change in anxiety severity measured by CGI-S	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.	Baseline visit, 4-week visit and 8-week visit.
Secondary	Change of anxiety symptoms measured with GAD-7	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).	Baseline visit, 4-week visit and 8-week visit.
Secondary	Change of anxiety symptoms measured with PSWQ	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).	Baseline visit, 4-week visit and 8-week visit.
Secondary	Change of anxiety symptoms measured with BAI	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).	Baseline visit, 4-week visit and 8-week visit.