Panic DisorderNCT04931134
Treatment of Anxiety Disorders With Trigeminal Nerve Stimulation
A study testing Trigeminal nerve stimulation - active in people with Panic Disorder and Generalized Anxiety Disorder, run by Dr. Rafael Freire at 1 site in Canada.
Trial summary
Primary objectives: The primary objective is to ascertain if trigeminal nerve stimulation is an effective treatment with high tolerability for patients with panic disorder, generalized anxiety disorder and social anxiety disorder. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Panic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder
- What is being tested?
- Trigeminal nerve stimulation - active
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteCanada
- Study dates
- 7 Feb 2022to 31 Jan 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 DSM5 criteria for panic disorder, social anxiety disorder or generalized anxiety disorder.
Who cannot join
- Subjects undergoing cognitive behavioural therapy.
- Subjects undergoing pharmacological treatment for an anxiety disorder.
- Subjects undergoing pharmacological treatment with antidepressants or benzodiazepines.
- Subjects with moderate to severe major depressive disorder based on the PHQ-9 test (score of 15 or above) at baseline.
- Moderate to high current suicidality or "suicide likely in near future" or current suicidal behavior disorder.
- Concurrent diagnosis of OCD, PTSD, bipolar disorder, schizophrenia, schizoaffective disorder, personality disorders, substance use disorders, intellectual disabilities or dementia.
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- Subjects diagnosed with neurological diseases including trigeminal neuralgia.
- Pregnant or breastfeeding women.
- Subjects who are experiencing seizures.
- Individuals with implanted VNS or other electrical devices.
- Subjects 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.
About this study
Official title: Trigeminal Nerve Stimulation in Anxiety Disorders: a Randomized Controlled Trial
Primary objectives: The primary objective is to ascertain if trigeminal nerve stimulation is an effective treatment with high tolerability for patients with panic disorder, generalized anxiety disorder and social anxiety disorder.
- Being tested
- Trigeminal nerve stimulation - active, Trigeminal nerve stimulation - sham
- Medical subject headings
- Panic Disorder, Generalized Anxiety Disorder, Phobia, Social
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trigeminal nerve stimulation - activeDevice
Active trigeminal nerve stimulation
Trigeminal nerve stimulation - shamDevice
Sham trigeminal nerve stimulation
| Study group | Role | What they receive |
|---|---|---|
| Active stimulation | Experimental | Active or sham TNS treatment will be performed at the patients' home for approximately 8 hours per night 7 days a week for 8 consecutive weeks.
Trigeminal nerve stimulation will occur by placement of electrodes (1.25" silver electrodes Bio-Flex BF4, Biotens/Vermed, Buffalo, NY, 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 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 - active |
| Sham stimulation | Sham comparator | Active or sham TNS treatment will be performed at the patients' home for approximately 8 hours per night 7 days a week for 8 consecutive weeks.
Sham stimulation will occur by placement of electrodes (1.25" silver electrodes Bio-Flex BF4, Biotens/Vermed, Buffalo, NY, 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 mA. Sham stimulation will use the same parameters of active stimulation, but after 60 seconds the stimulator will turn off. Receives: Device: Trigeminal nerve stimulation - sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response
Treatment response will be defined as a score of 1 or 2 on the Clinical Global Impression - Improvement scale (CGI-I). CGI-I scores range from 0 to 7. Zero corresponds to "not assessed". Low scores correspond to improvement, high scores correspond to worsening.
Measured: Clinical Global Impression - Improvement scale (CGI-I) will be administered after 8 weeks of treatment.
Remission
Remission will be defined as a score of 1 or 2 on the Clinical Global Impression - Severity scale (CGI-S). CGI-S scores range from 0 to 7. Zero corresponds to "not assessed". Low scores correspond to mild and high scores correspond to severe.
Measured: Clinical Global Impression - Severity scale (CGI-S) will be administered after 8 weeks of treatment.
Secondary outcomes (6)
Generalized anxiety disorder symptoms
Improvement of generalized anxiety disorder symptoms measured with the Generalized Anxiety Disorder 7-item scale (GAD-7). Scores go from 0 (no generalized anxiety symptoms) to 21 (severe generalized anxiety symptoms).
Measured: Generalized Anxiety Disorder 7-item scale (GAD-7) will be administered after 8 weeks of treatment.
Social anxiety disorder symptoms
Improvement of social anxiety disorder symptoms measured with the Social Phobia Inventory (SPIN). Scores go from 0 (no social anxiety symptoms) to 68 (severe social anxiety symptoms).
Measured: Social Phobia Inventory (SPIN) will be administered after 8 weeks of treatment.
Panic disorder symptoms
Improvement of panic disorder symptoms measured with the Panic Disorder Severity Scale - Self Report version (PDSS-SR). Scores go from 0 (no panic symptoms) to 4 (severe panic symptoms).
Measured: Panic Disorder Severity Scale - Self Report version (PDSS-SR) will be administered after 8 weeks of treatment.
Functioning
Improvement of functioning measured with the Sheehan Disability Scale (SDS). Scores go from 0 (no functional impairment) to 10 (severe functional impairment).
Measured: Sheehan Disability Scale (SDS) will be administered after 8 weeks of treatment.
Sustained response
Treatment response will be defined as a score of 1 or 2 on the Clinical Global Impression - Improvement scale (CGI-I).
CGI-I scores range from 0 to 7. Zero corresponds to "not assessed". Low scores correspond to improvement, high scores correspond to worsening.
Measured: Clinical Global Impression - Improvement scale (CGI-I) will be administered two weeks after the end of the treatment.
Sustained remission
Remission will be defined as a score of 1 or 2 on the Clinical Global Impression - Severity scale (CGI-S).
CGI-S scores range from 0 to 7. Zero corresponds to "not assessed". Low scores correspond to mild and high scores correspond to severe.
Measured: Clinical Global Impression - Severity scale (CGI-S) will be administered two weeks after the end of the treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start7 Feb 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Panic 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
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
- NCT04931134
- Sponsor's protocol ID
- 6028648
- Status last verified
- Apr 2025
- First submitted
- 7 Jun 2021
- Last updated
- 8 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
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 Anxiety Disorders: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04931134
- Acronym / sponsor ID
- 6028648
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Dr. Rafael FreireUniversity, hospital or other
- Study start
- 7 Feb 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Jan 2026 (estimated)
- First posted
- 18 Jun 2021 (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.
Primary objectives: The primary objective is to ascertain if trigeminal nerve stimulation is an effective treatment with high tolerability for patients with panic disorder, generalized anxiety disorder and social anxiety disorder.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active stimulation | Experimental | Device: Trigeminal nerve stimulation - activeActive or sham TNS treatment will be performed at the patients' home for approximately 8 hours per night 7 days a week for 8 consecutive weeks. Trigeminal nerve stimulation will occur by placement of electrodes (1.25" silver electrodes Bio-Flex BF4, Biotens/Vermed, Buffalo, NY, 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 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. |
| Sham stimulation | Sham comparator | Device: Trigeminal nerve stimulation - shamActive or sham TNS treatment will be performed at the patients' home for approximately 8 hours per night 7 days a week for 8 consecutive weeks. Sham stimulation will occur by placement of electrodes (1.25" silver electrodes Bio-Flex BF4, Biotens/Vermed, Buffalo, NY, 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 mA. Sham stimulation will use the same parameters of active stimulation, but after 60 seconds the stimulator will turn off. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Meet DSM5 criteria for panic disorder, social anxiety disorder or generalized anxiety disorder.
Key exclusion criteria (13 listed)
- Subjects undergoing cognitive behavioural therapy.
- Subjects undergoing pharmacological treatment for an anxiety disorder.
- Subjects undergoing pharmacological treatment with antidepressants or benzodiazepines.
- Subjects with moderate to severe major depressive disorder based on the PHQ-9 test (score of 15 or above) at baseline.
- Moderate to high current suicidality or "suicide likely in near future" or current suicidal behavior disorder.
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 stimulation - activeActive trigeminal nerve stimulation | Device | Active stimulation |
| Trigeminal nerve stimulation - shamSham trigeminal nerve stimulation | Device | Sham stimulation |
Primary outcome
Response
Time frame: Clinical Global Impression - Improvement scale (CGI-I) will be administered after 8 weeks of treatment.
Treatment response will be defined as a score of 1 or 2 on the Clinical Global Impression - Improvement scale (CGI-I). CGI-I scores range from 0 to 7. Zero corresponds to "not assessed". Low scores correspond to improvement, high scores correspond to worsening.
Remission
Time frame: Clinical Global Impression - Severity scale (CGI-S) will be administered after 8 weeks of treatment.
Remission will be defined as a score of 1 or 2 on the Clinical Global Impression - Severity scale (CGI-S). CGI-S scores range from 0 to 7. Zero corresponds to "not assessed". Low scores correspond to mild and high scores correspond to severe.
6 secondary outcomes
Generalized anxiety disorder symptoms
Time frame: Generalized Anxiety Disorder 7-item scale (GAD-7) will be administered after 8 weeks of treatment.
Social anxiety disorder symptoms
Time frame: Social Phobia Inventory (SPIN) will be administered after 8 weeks of treatment.
Panic disorder symptoms
Time frame: Panic Disorder Severity Scale - Self Report version (PDSS-SR) will be administered after 8 weeks of treatment.
Functioning
Time frame: Sheehan Disability Scale (SDS) will be administered after 8 weeks of treatment.
Sustained response
Time frame: Clinical Global Impression - Improvement scale (CGI-I) will be administered two weeks after the end of the treatment.
Sustained remission
Time frame: Clinical Global Impression - Severity scale (CGI-S) will be administered two weeks after the end of the treatment.
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.
- 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. This study is not recruiting at the moment.
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 - active in people with Panic Disorder and 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 1 inclusion and 13 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: under way, not looking for participants, 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. Some participants in this study may receive a placebo. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response (time frame: Clinical Global Impression - Improvement scale (CGI-I) will be administered after 8 weeks of treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.