Major Depressive Disorder (MDD)NCT07615387
Electrophysiological Biomarkers in Accelerated TMS for Depression
A study testing Accelerated bilateral dmPFC-iTBS in people with Major Depressive Disorder (MDD), run by Istanbul University - Cerrahpasa at 1 site in Turkey (Türkiye).
Trial summary
This study investigates whether physiological signals recorded during transcranial magnetic stimulation (TMS) can predict which patients with major depression respond to treatment. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- Accelerated bilateral dmPFC-iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 13 Jun 2024to 14 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Adults aged 18 to 65 years
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of major depressive disorder, of at least moderate severity, confirmed by structured psychiatric interview
- Insufficient response to at least one adequate trials of antidepressant pharmacotherapy during the current episode
- Stable psychotropic medication regimen for at least 4 weeks prior to enrollment
- Ability to provide written informed consent
Who cannot join
- Cardiac arrhythmia or use of antiarrhythmic medication
- Benzodiazepine use exceeding the equivalent of 1 mg/day lorazepam
- Active suicidal ideation
- Comorbid psychiatric disorders other than anxiety disorders (including bipolar disorder, psychotic disorders, substance use disorders, and primary obsessive-compulsive disorder)
- Standard contraindications to transcranial magnetic stimulation, including history of seizure, intracranial metal implants, cochlear implants, or implanted neurostimulators
- Pregnancy
- Severe or unstable medical illness
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Istanbul University-Cerrahpaşa Cerrahpaşa Medical Faculty Psychiatry Department
Istanbul, Bakırköy
About this study
Official title: Electrophysiological Biomarkers of Treatment Response in Major Depressive Disorder Patients Receiving Accelerated Transcranial Magnetic Stimulation
This study investigates whether physiological signals recorded during transcranial magnetic stimulation (TMS) can predict which patients with major depression respond to treatment. Thirty-two adults with major depressive disorder receive an accelerated TMS protocol targeting the dorsomedial prefrontal cortex using a double-cone coil, delivered as four sessions per day over five to eight days. Heart rate is continuously monitored throughout every stimulation session using a chest-strap sensor, and electroencephalography (EEG) is recorded before and after treatment. Heart-brain coupling was assessed in a separate dedicated session after the target stimulation dose was reached.The primary clinical outcome is the change in depression severity measured by the Hamilton Depression Rating Scale (HAMD-17) from baseline to post-treatment. Prespecified physiological outcomes include stimulation-evoked heart rate deceleration, resting-state EEG parameters, and heart-brain coupling metrics. The aim is to evaluate whether these electrophysiological measures index target engagement and predict antidepressant response, potentially supporting their use as functional biomarkers for personalizing accelerated TMS in depression.
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- Accelerated bilateral dmPFC-iTBS
- 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.
Accelerated bilateral dmPFC-iTBSDevice
Stimulation was delivered using a MagPro R30 stimulator equipped with a Cool DB-80 double-cone coil (MagVenture A/S, Farum, Denmark). The stimulation site was localized using the 25% nasion-inion scalp heuristic for dorsomedial prefrontal cortex (dmPFC) targeting. The intermittent theta-burst stimulation (iTBS) protocol consisted of triplet 50 Hz bursts repeated at 5 Hz, applied as 2-second trains with 8-second inter-train intervals. Each session delivered 600 pulses sequentially to the left and right dmPFC (1,200 pulses per session), at a target intensity of 120% of the hemisphere-specific resting motor threshold. Four sessions were delivered per day with approximately 50-minute inter-session intervals. The total treatment course was 20 sessions over 5 days, extended to 30 sessions over 8 days for partial responders.
| Study group | Role | What they receive |
|---|---|---|
| Accelerated bilateral dmPFC-iTBS with double-cone coil | Experimental | Participants received accelerated bilateral intermittent theta-burst stimulation (iTBS) targeting the dorsomedial prefrontal cortex (dmPFC) using a Cool DB-80 double-cone coil. Treatment consisted of four sessions per day, delivering 1,200 pulses per session (600 pulses per hemisphere, applied sequentially to left and right dmPFC), at 120% of resting motor threshold. The total course comprised 20 to 30 sessions over 5 to 8 days. Receives: Device: Accelerated bilateral dmPFC-iTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hamilton Depression Rating Scale (HAMD-17) Score
Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and within 1 week after completion of the accelerated iTBS course. The HAMD-17 is a clinician-administered scale; scores range from 0 to 52, with higher scores indicating more severe depression. Treatment response was defined as a 50% or greater reduction from baseline HAMD-17 score, and remission as a post-treatment HAMD-17 score of 7 or lower.
Measured: Baseline, Day 5, and Day 8 for extended courses
Secondary outcomes (10)
Heart rate deceleration during stimulation
Heart rate was continuously sampled at 1-second intervals using a Polar H10 chest strap during every stimulation session. Heart rate deceleration (HRD) was calculated as the percentage reduction from the 1-minute pre-stimulation baseline heart rate to the mean stimulation heart rate, using the formula: HRD (%) = [(HR_baseline - HR_stimulation) / HR_baseline] x 100. HRD was computed across four parameters (all left-sided sessions, all right-sided sessions, highest-intensity left-sided sessions, highest-intensity right-sided sessions) and averaged per participant. Higher values indicate greater stimulation-induced heart rate deceleration.
Measured: Through completion of the treatment course, up to 8 days
Change in Beck Depression Inventory (BDI)
Beck Depression Inventory (BDI), a self-report scale; total scores range from 0 to 63, with higher scores indicating more severe depression.
Measured: Baseline, Day 5, and Day 8 for extended courses
Change in Beck Anxiety Inventory (BAI)
Beck Anxiety Inventory (BAI), a self-report scale; total scores range from 0 to 63, with higher scores indicating more severe anxiety.
Measured: Baseline, Day 5, and Day 8 for extended courses
Change in Beck Scale for Suicide Ideation (BSS)
Beck Scale for Suicide Ideation (BSS), a self-report scale; total scores range from 0 to 38, with higher scores indicating greater suicidal ideation.
Measured: Baseline, Day 5, and Day 8 for extended courses
Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) Total Score
Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16); total scores range from 0 to 27, with higher scores indicating more severe depression.
Measured: Baseline, Day 5, and Day 8 for extended courses
Change in Clinical Global Impression - Severity (CGI-S)
Clinical Global Impression - Severity (CGI-S); scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients), with higher scores indicating greater illness severity.
Measured: Baseline, Day 5, and Day 8 for extended courses
Hamilton Depression Rating Scale (HAMD-17) Total Score at 30-Day Follow-up
17-item Hamilton Depression Rating Scale (HAMD-17) assessed 30 days after completion of treatment; total scores range from 0 to 52, with higher scores indicating more severe depression.
Measured: 30 days post-treatment
Resting State Quantitative EEG (qEEG) Spectral Power and Theta Cordance
Absolute spectral power in the delta, theta, alpha, and beta frequency bands, derived from quantitative resting-state EEG (qEEG) analysis. Power was computed across standard electrode regions. Prefrontal theta cordance, a quantitative EEG measure combining absolute and relative theta-band power at prefrontal electrodes, derived from resting-state qEEG analysis.
Measured: Baseline and completion of treatment (Day5 or Day8 for extended courses)
Heart-Brain Coupling (HBC): Heart Rate Oscillation Power at the Stimulation Frequency
Heart-brain coupling (HBC), a parameter quantifying the strength of stimulation-induced heart rate deceleration, computed as the mean oscillation power of cardiac rate at the frequency determined by the stimulation train interval (Dijkstra et al., 2023). HBC ranges from 0 to 1. Measurements were obtained in a dedicated session using a 10 Hz protocol (50 pulses per train, 5-second train duration, 15 trains, 11-second inter-train interval), recorded with a Polar H10 chest strap and the HeartBrainConnect application. HBC was assessed sequentially at four sites per participant: left dmPFC, left dorsolateral prefrontal cortex (DLPFC), right dmPFC and right DLPFC. For each site, stimulation began at 28% below target intensity and increased by 2% per train, yielding 15 HBC values that were averaged to produce a per-site HBC value.
Measured: Single dedicated measurement session after the target dose was reached, up to Day 8
EEG Microstate Temporal Parameters
Temporal parameters of the canonical resting-state EEG microstate classes (A, B, C, and D), including mean duration (milliseconds), occurrence (mean appearances per second), time coverage (percentage of recording time), and transition probabilities between classes. Parameters were derived from microstate segmentation of resting-state EEG recordings.
Measured: Baseline and completion of treatment (Day5 or Day8 for extended courses)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2026
- Study start13 Jun 2024
- Primary completion14 Mar 2025
- Study completion14 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- More trials run by Istanbul University - CerrahpasaThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istanbul University - Cerrahpasa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ali Tarık Altunç, Istanbul University - Cerrahpasa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07615387
- Sponsor's protocol ID
- 37949
- Status last verified
- May 2026
- First submitted
- 18 May 2026
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: De-identified individual-level data are not publicly available due to privacy and ethical restrictions on sensitive clinical data, but may be available from the corresponding author upon reasonable request and with appropriate ethics committee approval.
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrophysiological Biomarkers of Treatment Response in Major Depressive Disorder Patients Receiving Accelerated Transcranial Magnetic Stimulation
- ClinicalTrials.gov ID
- NCT07615387
- Acronym / sponsor ID
- 37949
- Conditions
- Major Depressive Disorder (MDD)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Istanbul University - CerrahpasaUniversity, hospital or other
- Study start
- 13 Jun 2024 (actual)
- Primary completion
- 14 Mar 2025 (actual)
- Study completion
- 14 Apr 2025 (actual)
- First posted
- 29 May 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 investigates whether physiological signals recorded during transcranial magnetic stimulation (TMS) can predict which patients with major depression respond to treatment. Thirty-two adults with major depressive disorder receive an accelerated TMS protocol targeting the dorsomedial prefrontal cortex using a double-cone coil, delivered as four sessions per day over five to eight days. Heart rate is continuously monitored throughout every stimulation session using a chest-strap sensor, and electroencephalography (EEG) is recorded before and after treatment. Heart-brain coupling was assessed in a separate dedicated session after the target stimulation dose was reached.The primary clinical outcome is the change in depression severity measured by the Hamilton Depression Rating Scale (HAMD-17) from baseline to post-treatment. Prespecified physiological outcomes include stimulation-evoked heart rate deceleration, resting-state EEG parameters, and heart-brain coupling metrics. The aim is to evaluate whether these electrophysiological measures index target engagement and predict antidepressant response, potentially supporting their use as functional biomarkers for personalizing accelerated TMS in depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Accelerated bilateral dmPFC-iTBS with double-cone coil | Experimental | Device: Accelerated bilateral dmPFC-iTBSParticipants received accelerated bilateral intermittent theta-burst stimulation (iTBS) targeting the dorsomedial prefrontal cortex (dmPFC) using a Cool DB-80 double-cone coil. Treatment consisted of four sessions per day, delivering 1,200 pulses per session (600 pulses per hemisphere, applied sequentially to left and right dmPFC), at 120% of resting motor threshold. The total course comprised 20 to 30 sessions over 5 to 8 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults aged 18 to 65 years
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of major depressive disorder, of at least moderate severity, confirmed by structured psychiatric interview
- Insufficient response to at least one adequate trials of antidepressant pharmacotherapy during the current episode
- Stable psychotropic medication regimen for at least 4 weeks prior to enrollment
- Ability to provide written informed consent
Key exclusion criteria (7 listed)
- Cardiac arrhythmia or use of antiarrhythmic medication
- Benzodiazepine use exceeding the equivalent of 1 mg/day lorazepam
- Active suicidal ideation
- Comorbid psychiatric disorders other than anxiety disorders (including bipolar disorder, psychotic disorders, substance use disorders, and primary obsessive-compulsive disorder)
- Standard contraindications to transcranial magnetic stimulation, including history of seizure, intracranial metal implants, cochlear implants, or implanted neurostimulators
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 |
|---|---|---|
| Accelerated bilateral dmPFC-iTBSStimulation was delivered using a MagPro R30 stimulator equipped with a Cool DB-80 double-cone coil (MagVenture A/S, Farum, Denmark). The stimulation site was localized using the 25% nasion-inion scalp heuristic for dorsomedial prefrontal cortex (dmPFC) targeting. The intermittent theta-burst stimulation (iTBS) protocol consisted of triplet 50 Hz bursts repeated at 5 Hz, applied as 2-second trains with 8-second inter-train intervals. Each session delivered 600 pulses sequentially to the left and right dmPFC (1,200 pulses per session), at a target intensity of 120% of the hemisphere-specific resting motor threshold. Four sessions were delivered per day with approximately 50-minute inter-session intervals. The total treatment course was 20 sessions over 5 days, extended to 30 sessions over 8 days for partial responders. | Device | Accelerated bilateral dmPFC-iTBS with double-cone coil |
Primary outcome
Change in Hamilton Depression Rating Scale (HAMD-17) Score
Time frame: Baseline, Day 5, and Day 8 for extended courses
Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and within 1 week after completion of the accelerated iTBS course. The HAMD-17 is a clinician-administered scale; scores range from 0 to 52, with higher scores indicating more severe depression. Treatment response was defined as a 50% or greater reduction from baseline HAMD-17 score, and remission as a post-treatment HAMD-17 score of 7 or lower.
10 secondary outcomes
Heart rate deceleration during stimulation
Time frame: Through completion of the treatment course, up to 8 days
Change in Beck Depression Inventory (BDI)
Time frame: Baseline, Day 5, and Day 8 for extended courses
Change in Beck Anxiety Inventory (BAI)
Time frame: Baseline, Day 5, and Day 8 for extended courses
Change in Beck Scale for Suicide Ideation (BSS)
Time frame: Baseline, Day 5, and Day 8 for extended courses
Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) Total Score
Time frame: Baseline, Day 5, and Day 8 for extended courses
Change in Clinical Global Impression - Severity (CGI-S)
Time frame: Baseline, Day 5, and Day 8 for extended courses
Hamilton Depression Rating Scale (HAMD-17) Total Score at 30-Day Follow-up
Time frame: 30 days post-treatment
Resting State Quantitative EEG (qEEG) Spectral Power and Theta Cordance
Time frame: Baseline and completion of treatment (Day5 or Day8 for extended courses)
Heart-Brain Coupling (HBC): Heart Rate Oscillation Power at the Stimulation Frequency
Time frame: Single dedicated measurement session after the target dose was reached, up to Day 8
EEG Microstate Temporal Parameters
Time frame: Baseline and completion of treatment (Day5 or Day8 for extended courses)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Individual participant dataSharing planned: No. De-identified individual-level data are not publicly available due to privacy and ethical restrictions on sensitive clinical data, but may be available from the corresponding author upon reasonable request and with appropriate ethics committee approval.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Accelerated bilateral dmPFC-iTBS in people with Major Depressive Disorder (MDD), run by Istanbul University - Cerrahpasa at 1 site in Turkey (Türkiye).
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 7 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: finished, as of the sponsor's last update on 29 May 2026. 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 Turkey (Türkiye). 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Hamilton Depression Rating Scale (HAMD-17) Score (time frame: Baseline, Day 5, and Day 8 for extended courses). 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 29 May 2026.