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

NCT ID: NCT06278909

Last Updated: 2025-04-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-18

Study Completion Date

2026-04-01

Brief Summary

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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

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Conditions

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Generalized Anxiety Disorder

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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

TREATMENT

Blinding Strategy

NONE

Study Groups

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Active stimulation

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.

Group Type EXPERIMENTAL

Trigeminal Nerve Stimulation

Intervention Type DEVICE

Active trigeminal nerve stimulation

Interventions

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Trigeminal Nerve Stimulation

Active trigeminal nerve stimulation

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dr. Rafael Freire

OTHER

Sponsor Role lead

Responsible Party

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Dr. Rafael Freire

Associate Professor, Department of Psychiatry

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Rafael Freire, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Psychiatry, Queen's University

Locations

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Kingston Health Sciences Centre

Kingston, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Yan Deng

Role: CONTACT

+1 613-548-7839

Rafael Freire, MD PhD

Role: CONTACT

+1 613-548-7839

Facility Contacts

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Yan Deng

Role: primary

+1-613-548-7839

References

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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.

Reference Type BACKGROUND
PMID: 26818103 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23773978 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32002936 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25650095 (View on PubMed)

Other Identifiers

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6036699

Identifier Type: -

Identifier Source: org_study_id

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