Generalized Anxiety DisorderNCT06278909
Trigeminal Nerve Stimulation in Treatment-resistant Generalized Anxiety Disorder: a Feasibility Study
A study testing Trigeminal Nerve Stimulation in people with Generalized Anxiety Disorder, run by Dr. Rafael Freire at 1 site in Canada.
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Generalized Anxiety Disorder
- What is being tested?
- Trigeminal Nerve Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- 18 Jan 2024to 1 Apr 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Kingston Health Sciences Centre
Kingston, Ontario
Yan Deng, +1-613-548-7839, yan.deng@queensu.ca
Rafael Freire, MD PhD
About this study
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
- Being tested
- Trigeminal Nerve Stimulation
- Medical subject headings
- Generalized Anxiety Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trigeminal Nerve StimulationDevice
Active trigeminal nerve stimulation
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Trigeminal Nerve Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events
Monitor participants for treatment-emergent adverse events and serious adverse events.
Measured: 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).
Measured: 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.
Measured: 4-week visit and 8-week visit.
Secondary outcomes (5)
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.
Measured: 4-week visit and 8-week visit.
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.
Measured: Baseline visit, 4-week visit and 8-week visit.
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).
Measured: Baseline visit, 4-week visit and 8-week visit.
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).
Measured: Baseline visit, 4-week visit and 8-week visit.
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).
Measured: Baseline visit, 4-week visit and 8-week visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2024
- Study start18 Jan 2024
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Generalized Anxiety DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a traditional feasibility study, which evaluates preliminary safety and effectiveness information. It does not meet the definition of a "device feasibility" study.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr. Rafael Freire
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Rafael Freire, Queen's University
- Investigators
- Rafael Freire, MD PhD, Principal investigator, Department of Psychiatry, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06278909
- Sponsor's protocol ID
- 6036699
- Status last verified
- Apr 2025
- First submitted
- 9 Feb 2024
- Last updated
- 8 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 26818103Cook 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.
PubMed 23773978Freire 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.
PubMed 32002936Trevizol 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.
PubMed 25650095
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trigeminal Nerve Stimulation in Treatment-resistant Generalized Anxiety Disorder: a Feasibility Study
- ClinicalTrials.gov ID
- NCT06278909
- Acronym / sponsor ID
- 6036699
- Conditions
- Generalized Anxiety Disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Dr. Rafael FreireUniversity, hospital or other
- Study start
- 18 Jan 2024 (actual)
- Primary completion
- 1 Mar 2026 (estimated)
- Study completion
- 1 Apr 2026 (estimated)
- First posted
- 26 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a traditional feasibility study, which evaluates preliminary safety and effectiveness information. It does not meet the definition of a "device feasibility" study.
| Arm | Type | Receives |
|---|---|---|
| Active stimulation | Experimental | Device: Trigeminal Nerve StimulationTrigeminal 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trigeminal Nerve StimulationActive trigeminal nerve stimulation | Device | Active stimulation |
Primary outcome
Incidence of treatment-emergent adverse events
Time frame: Throughout the study, 8 weeks
Monitor participants for treatment-emergent adverse events and serious adverse events.
Incidence of treatment-emergent side effects measured with the NSEC
Time frame: 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).
Response to treatment defined by CGI-I score below 3
Time frame: 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.
5 secondary outcomes
Remission defined by CGI-S score below 3
Time frame: 4-week visit and 8-week visit.
Change in anxiety severity measured by CGI-S
Time frame: Baseline visit, 4-week visit and 8-week visit.
Change of anxiety symptoms measured with GAD-7
Time frame: Baseline visit, 4-week visit and 8-week visit.
Change of anxiety symptoms measured with PSWQ
Time frame: Baseline visit, 4-week visit and 8-week visit.
Change of anxiety symptoms measured with BAI
Time frame: Baseline visit, 4-week visit and 8-week visit.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
- Background: PubMed 26818103Cook 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.
- Background: PubMed 23773978Cook 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.
- Background: PubMed 32002936Freire 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.
- Background: PubMed 25650095Trevizol 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rafael Freire, MD PhD principal investigator
Department of Psychiatry, Queen's University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Trigeminal Nerve Stimulation in people with Generalized Anxiety Disorder, run by Dr. Rafael Freire at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yan Deng (+1 613-548-7839, yan.deng@queensu.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent adverse events (time frame: Throughout the study, 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06278909, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2025.