MDDNCT07629050
Functional Electrical Stimulation for MDD
A study testing Functional Electrical Stimulation (FES) in people with MDD, run by Unity Health Toronto.
Trial summary
This study aims to determine whether Functional Electrical Stimulation (FES) of the facial muscles is a safe and effective treatment for major depressive disorder (MDD). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- MDD
- What is being tested?
- Functional Electrical Stimulation (FES)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 25 May 2026to 30 Mar 2029
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be included if they:
- Meet the DSM-5 criteria for unipolar MDD with a current MDE without psychotic features, with ≤ 2 failed treatment trials (non-treatment-resistant depression), validated by MINI done by a trained research assistant.
- Have no change in the medication regimen or other forms of treatments (e.g., psychotherapy) for at least 4 weeks (28 days) prior to beginning the study, and have no plan to change them during the 20-session treatment period (14 days), and the 4-week post-treatment observation period. This will be established through self-report, in combination with the ATHF filled out by the participant.
- Have an MDD diagnosis as confirmed by the MADRS score of ≥7.
- Age group between 18 and 70 years of age
Who cannot join
- Patients will be excluded if they:
- History of epilepsy or seizures.
- Damage or dysfunction of facial nerves.
- Metallic orthopedic implants in the mouth (e.g., plates or screws).
- Current fibromyalgia or currently receiving or have received rTMS within the last 28 days before the screening.
- History of treatment-resistant depression (TRD) with history of ECT, Magnetic Seizure Therapy, Intravenous Ketamine use in the past or failure of >2 antidepressant treatments of adequate duration and dose during the current episode.
Show all 10Show fewer
- Past or current symptoms of mania, hypomania, mixed episodes, psychotic disorders, obsessive-compulsive disorder, post-traumatic stress disorder, active substance abuse or dependence (excluding nicotine and caffeine), neurodegenerative disease, or dementia. This will be confirmed on the MINI (77) administered by a trained research assistant.
- Current suicidal intent or plan as demonstrated by a score of ≥4 on MADRS item 10.
- Unable to understand instructions in English.
- Unable to produce "Duchenne marker" expression with FES, secondary to any type of neurological condition or previous botulinum toxin treatments of facial muscles.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Functional Electrical Stimulation for Major Depressive Disorder: A Pilot Randomized Control Trial
This study aims to determine whether Functional Electrical Stimulation (FES) of the facial muscles is a safe and effective treatment for major depressive disorder (MDD).
Read the detailed description
A potential new treatment for Major Depressive Disorder (MDD) involves using a Functional Electrical Stimulation (FES) device to stimulate specific facial muscles. By targeting muscles related to smile patterns, FES has shown promise in improving emotional control and boosting mood. This project aims to address a critical need for innovative treatments for MDD, especially since 30% of MDD patients do not respond to traditional treatments.
This is a single-site clinical trial that is double-blind, randomized, and sham-controlled, involving 20 sessions of FES over four weeks. The trial will assess the effectiveness, safety, and tolerability of FES for individuals with mild-to-moderate major depressive episode (MDE) and a primary diagnosis of MDD.
Participants in the study will have a total of 26 visits: one screening and one baseline visit (both conducted by phone), followed by 20 on-site intervention visits over four weeks (one sessions per day). After the treatment, there will also be four follow-up visits over the phone to check how long the effects of the FES treatment last.
- Conditions
- MDD
- Being tested
- Functional Electrical Stimulation (FES)
- Keywords
- Major Depressive Disorder, Functional Electrical Stimulation
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Functional Electrical Stimulation (FES)Device
Once per day for the duration of 4 weeks. Total of 20 sessions (each session lasts 60 mins)
| Study group | Role | What they receive |
|---|---|---|
| Active FES | Experimental | Functional Electrical Stimulation (FES) will be administered to four facial muscles involved in smiling, with two muscles targeted on each side of the face. Electrodes will be placed over the target muscles, and stimulation will be delivered using standard muscle-activation settings. Receives: Device: Functional Electrical Stimulation (FES) |
| Sham FES | Sham comparator | Sham Functional Electrical Stimulation (FES) will be administered using the same electrode placement and session schedule as the active FES arm. Stimulation will be delivered at a low sensory intensity range of 1-8 mA, sufficient for participants to feel the stimulation, while other parameters will remain the same as in the active arm. Sham stimulation will be delivered in a non-Duchenne smile pattern. Receives: Device: Functional Electrical Stimulation (FES) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of FES: Change in Depression Severity
Change in depression severity measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17). Scores range from 0 to 52, with higher scores indicating more severe depressive symptoms.
Measured: 4 weeks of Intervention, 4 weeks of follow-up
Tolerability of FES
The overall dropout and protocol compliance rates will be assessed.
Measured: 4 weeks of Intervention, 4 weeks of follow-up
FES safety
The number and nature of adverse events will be assessed
Measured: 4 weeks of Intervention, 4 weeks of follow-up
Secondary outcomes (5)
Change in Anxiety Symptoms
Anxiety symptoms will be assessed using the Generalized Anxiety Disorder-7. Total scores range from 0 to 21, with higher scores indicating greater anxiety symptom severity.
Measured: 4 weeks of Intervention, 4 weeks of follow-up
Change in Well-Being
Well-being will be assessed using the World Health Organization-Five Well-Being Index. Raw total scores range from 0 to 25, with higher scores indicating better well-being.
Measured: 4 weeks of Intervention, 4 weeks of follow-up
Change in Sleep Quality
Sleep quality will be assessed using the Pittsburgh Sleep Quality Index. Global scores range from 0 to 21, with higher scores indicating poorer sleep quality.
Measured: 4 weeks of Intervention, 4 weeks of follow-up
Response and Remission Rate
Response and Remission will be assessed using the 17-item Hamilton Depression Rating Scale. Total scores on the 17-item Hamilton Depression Rating Scale range from 0 to 52, with higher scores indicating greater depression symptom severity.
Measured: 4 weeks of Intervention, 4 weeks of follow-up
Changes in Facial Expressivity
Changes in facial expressivity (frequency, intensity and duration of Duchenne smiles) will be assessed during an emotional interview, using objective facial coding.
Measured: 4 weeks of Intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2026
- Study start25 May 2026 (estimated)
- Primary completion20 Apr 2028 (estimated)
- Study completion30 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MDDStudies 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07629050
- Sponsor's protocol ID
- 24-155
- Other IDs
- WI4 179978
- Status last verified
- Mar 2026
- First submitted
- 25 May 2026
- Last updated
- 8 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gholamali Nezhad F, Yu H, Demchenko I, Iwasa SN, DiNunzio S, Ghosh R, Zariffa J, Masani K, Lou W, Mulsant BH, Naguib HE, Popovic MR, Bhat V. Functional electrical stimulation for major depressive disorder: Protocol for a pilot randomized controlled trial. PLoS One. 2026 Sep 10;21(9):e0357381. doi: 10.1371/journal.pone.0357381. eCollection 2026.
PubMed 42721198
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Electrical Stimulation for Major Depressive Disorder: A Pilot Randomized Control Trial
- ClinicalTrials.gov ID
- NCT07629050
- Acronym / sponsor ID
- 24-155
- Conditions
- MDD
- Keywords
- Major Depressive Disorder, Functional Electrical Stimulation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 25 May 2026 (estimated)
- Primary completion
- 20 Apr 2028 (estimated)
- Study completion
- 30 Mar 2029 (estimated)
- First posted
- 5 Jun 2026 (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 study aims to determine whether Functional Electrical Stimulation (FES) of the facial muscles is a safe and effective treatment for major depressive disorder (MDD).
Detailed description
A potential new treatment for Major Depressive Disorder (MDD) involves using a Functional Electrical Stimulation (FES) device to stimulate specific facial muscles. By targeting muscles related to smile patterns, FES has shown promise in improving emotional control and boosting mood. This project aims to address a critical need for innovative treatments for MDD, especially since 30% of MDD patients do not respond to traditional treatments.
This is a single-site clinical trial that is double-blind, randomized, and sham-controlled, involving 20 sessions of FES over four weeks. The trial will assess the effectiveness, safety, and tolerability of FES for individuals with mild-to-moderate major depressive episode (MDE) and a primary diagnosis of MDD.
Participants in the study will have a total of 26 visits: one screening and one baseline visit (both conducted by phone), followed by 20 on-site intervention visits over four weeks (one sessions per day). After the treatment, there will also be four follow-up visits over the phone to check how long the effects of the FES treatment last.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active FES | Experimental | Device: Functional Electrical Stimulation (FES)Functional Electrical Stimulation (FES) will be administered to four facial muscles involved in smiling, with two muscles targeted on each side of the face. Electrodes will be placed over the target muscles, and stimulation will be delivered using standard muscle-activation settings. |
| Sham FES | Sham comparator | Device: Functional Electrical Stimulation (FES)Sham Functional Electrical Stimulation (FES) will be administered using the same electrode placement and session schedule as the active FES arm. Stimulation will be delivered at a low sensory intensity range of 1-8 mA, sufficient for participants to feel the stimulation, while other parameters will remain the same as in the active arm. Sham stimulation will be delivered in a non-Duchenne smile pattern. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Meet the DSM-5 criteria for unipolar MDD with a current MDE without psychotic features, with ≤ 2 failed treatment trials (non-treatment-resistant depression), validated by MINI done by a trained research assistant.
- Have no change in the medication regimen or other forms of treatments (e.g., psychotherapy) for at least 4 weeks (28 days) prior to beginning the study, and have no plan to change them during the 20-session treatment period (14 days), and the 4-week post-treatment observation period. This will be established through self-report, in combination with the ATHF filled out by the participant.
- Have an MDD diagnosis as confirmed by the MADRS score of ≥7.
- Age group between 18 and 70 years of age
Key exclusion criteria (10 listed)
- History of epilepsy or seizures.
- Damage or dysfunction of facial nerves.
- Metallic orthopedic implants in the mouth (e.g., plates or screws).
- Current fibromyalgia or currently receiving or have received rTMS within the last 28 days before the screening.
- History of treatment-resistant depression (TRD) with history of ECT, Magnetic Seizure Therapy, Intravenous Ketamine use in the past or failure of >2 antidepressant treatments of adequate duration and dose during the current episode.
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 |
|---|---|---|
| Functional Electrical Stimulation (FES)Once per day for the duration of 4 weeks. Total of 20 sessions (each session lasts 60 mins) | Device | Active FES, Sham FES |
Primary outcome
Efficacy of FES: Change in Depression Severity
Time frame: 4 weeks of Intervention, 4 weeks of follow-up
Change in depression severity measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17). Scores range from 0 to 52, with higher scores indicating more severe depressive symptoms.
Tolerability of FES
Time frame: 4 weeks of Intervention, 4 weeks of follow-up
The overall dropout and protocol compliance rates will be assessed.
FES safety
Time frame: 4 weeks of Intervention, 4 weeks of follow-up
The number and nature of adverse events will be assessed
5 secondary outcomes
Change in Anxiety Symptoms
Time frame: 4 weeks of Intervention, 4 weeks of follow-up
Change in Well-Being
Time frame: 4 weeks of Intervention, 4 weeks of follow-up
Change in Sleep Quality
Time frame: 4 weeks of Intervention, 4 weeks of follow-up
Response and Remission Rate
Time frame: 4 weeks of Intervention, 4 weeks of follow-up
Changes in Facial Expressivity
Time frame: 4 weeks of Intervention
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 Jun 2026.
- Derived from this study: PubMed 42721198Gholamali Nezhad F, Yu H, Demchenko I, Iwasa SN, DiNunzio S, Ghosh R, Zariffa J, Masani K, Lou W, Mulsant BH, Naguib HE, Popovic MR, Bhat V. Functional electrical stimulation for major depressive disorder: Protocol for a pilot randomized controlled trial. PLoS One. 2026 Sep 10;21(9):e0357381. doi: 10.1371/journal.pone.0357381. eCollection 2026.
- 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.
Questions about this trial
What is this clinical trial studying?
A study testing Functional Electrical Stimulation (FES) in people with MDD, run by Unity Health Toronto.
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 5 inclusion and 10 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: opening soon, as of the sponsor's last update on 8 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
Contact Venkat Bhat (416-360-4000 ext. 76404, Venkat.Bhat@unityhealth.to), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of FES: Change in Depression Severity (time frame: 4 weeks of Intervention, 4 weeks of follow-up). 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 NCT07629050, which also lists 1 linked publication.
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 Jun 2026.