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

NCT06278909 | Recruiting FDA Device

• 1 other identifier: 6036699
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Generalized Anxiety Disorder

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment-emergent adverse events

  Monitor participants for treatment-emergent adverse events and serious adverse events.

  Throughout the study, 8 weeks

• 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.

• 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 Outcomes (5)

• Remission defined by CGI-S score below 3

  4-week visit and 8-week visit.

• Change in anxiety severity measured by CGI-S

  Baseline visit, 4-week visit and 8-week visit.

• Change of anxiety symptoms measured with GAD-7

  Baseline visit, 4-week visit and 8-week visit.

• Change of anxiety symptoms measured with PSWQ

  Baseline visit, 4-week visit and 8-week visit.

• Change of anxiety symptoms measured with BAI

  Baseline visit, 4-week visit and 8-week visit.

Study Arms (1)

Active stimulation

EXPERIMENTAL

Trigeminal nerve stimulation will occur by placement of electrodes (1.25" silver electrodes Bio-Flex BF4, Biotens/Vermed, Buffalo, New York, 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 milliampere (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

Interventions

Trigeminal Nerve Stimulation DEVICE

Active trigeminal nerve stimulation

Active stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. Rafael Freire: lead

Study Sites (1)

Kingston Health Sciences Centre

Kingston, Ontario, Canada

RECRUITING

Related 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.

  PMID: 26818103 BACKGROUND

• 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.

  PMID: 23773978 BACKGROUND

• 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.

  PMID: 32002936 BACKGROUND

• 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.

  PMID: 25650095 BACKGROUND

MeSH Terms

Conditions

Generalized Anxiety Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Study Officials

• Rafael Freire, MD PhD

  Department of Psychiatry, Queen's University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Deng

CONTACT

+1 613-548-7839; yan.deng@queensu.ca

Rafael Freire, MD PhD

CONTACT

+1 613-548-7839; rafael.freire@queensu.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Department of Psychiatry

Model Details: This is a traditional feasibility study, which evaluates preliminary safety and effectiveness information. It does not meet the definition of a "device feasibility" study.

Study Record Dates

• First Submitted: February 9, 2024
• First Posted: February 26, 2024
• Study Start: January 18, 2024
• Primary Completion: March 1, 2026
• Study Completion: April 1, 2026
• Last Updated: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)