Major Depressive Disorder (MDD)AIM-DNCT07603804
Accelerated iTBS for Major Depression
A study testing Accelerated Intermittent Theta Burst Stimulation (iTBS) in people with Major Depressive Disorder (MDD) and Treatment Resistant Depression (TRD), run by Istanbul University - Cerrahpasa at 1 site in Turkey (Türkiye).
Trial summary
Major depressive disorder (MDD) is a common and disabling psychiatric condition, and many patients do not achieve adequate response to standard antidepressant treatments. Accelerated intermittent theta burst stimulation (iTBS) is a promising neuromodulation approach that may provide rapid antidepressant effects. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder (MDD), Treatment Resistant Depression (TRD)
- What is being tested?
- Accelerated Intermittent Theta Burst Stimulation (iTBS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 8 Mar 2026to 31 Dec 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
- Age between 18 and 65 years
- Diagnosis of Major Depressive Disorder according to DSM-5 criteria
- Inadequate response to at least one adequate antidepressant treatment trial
- Hamilton Depression Rating Scale (HAM-D) score ≥14 at baseline
- Stable dose of antidepressant medication for at least 4 weeks prior to study entry
- Ability to provide written informed consent
Who cannot join
- History of bipolar disorder, schizophrenia, schizoaffective disorder, or psychotic depression
- Current substance use disorder
- Neurological disorders that may affect brain function (e.g., epilepsy, multiple sclerosis, dementia, Parkinson's disease)
- History of epileptic seizures
- Severe head trauma
- Presence of metal implants in the head or neck region
Show all 16Show fewer
- Cochlear implants
- Cardiac pacemaker or implanted electronic devices
- History of deep brain stimulation or vagus nerve stimulation
- Previous neurosurgical procedures
- Pregnancy or breastfeeding
- Use of medications that may significantly affect neuroendocrine or inflammatory markers (e.g., corticosteroids, immunomodulators)
- Endocrine disorders affecting the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome, Addison's disease, thyroid disorders)
- Autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, Hashimoto thyroiditis)
- Recent surgery or acute infection
- Active suicidal crisis, severe agitation, or inability to comply with study procedures
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Istanbul University - Cerrahpasa
Istanbul, 34000
Merve rANA Altunel Ülkü, MD, +90 506 303 10 68, ranaltunel@gmail.com
Cana Aksoy Poyraz, Prof. Dr., +90 532 715 95 04, aksoycana@gmail.com
About this study
Official title: Investigation of the Relationship Between Changes in Neurobiological Biomarkers After Accelerated Transcranial Magnetic Stimulation Treatment and Treatment Response in Patients With Major Depressive Disorder
Major depressive disorder (MDD) is a common and disabling psychiatric condition, and many patients do not achieve adequate response to standard antidepressant treatments. Accelerated intermittent theta burst stimulation (iTBS) is a promising neuromodulation approach that may provide rapid antidepressant effects. This prospective interventional study aims to evaluate the clinical effectiveness of accelerated bilateral dorsomedial prefrontal cortex iTBS in patients with MDD and to investigate treatment-related changes in neurobiological biomarkers, including cortisol, ACTH, BDNF, IL-1β, IL-6, TNF-α, and CRP. Associations between biomarker changes and treatment response will also be examined.
Read the detailed description
Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric disorder. A substantial proportion of patients do not achieve sufficient improvement with conventional antidepressant treatments, resulting in treatment-resistant or difficult-to-treat depression. Noninvasive neuromodulation approaches such as transcranial magnetic stimulation (TMS) have emerged as effective alternatives for these patients. Accelerated intermittent theta burst stimulation (iTBS), delivered in multiple daily sessions over a short period, may provide faster clinical improvement compared with conventional protocols.
This prospective single-arm interventional study aims to evaluate the clinical efficacy and biological correlates of accelerated bilateral dorsomedial prefrontal cortex (DMPFC) iTBS in adults with MDD who have shown inadequate response to at least one adequate antidepressant treatment trial.
Participants aged 18 to 65 years will receive accelerated bilateral DMPFC iTBS for five consecutive days, with four sessions per day (20 total sessions). Participants demonstrating partial clinical improvement without remission after 20 sessions may receive an additional 10 sessions according to clinical evaluation.
Clinical assessments will be performed at baseline, during treatment, at the end of treatment, and at one-month follow-up. Outcome measures include Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory, Beck Anxiety Inventory, suicidal ideation measures, self-rated depressive symptom scales, and Clinical Global Impression ratings.
Blood samples will be collected at baseline and after treatment to evaluate neurobiological biomarkers, including cortisol, adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP).
The primary objective is to determine treatment response based on reduction in depressive symptom severity. Secondary objectives are to examine biomarker changes associated with treatment, identify predictors of response, and explore the relationship between early symptom improvement and final clinical outcomes.
- Being tested
- Accelerated Intermittent Theta Burst Stimulation (iTBS)
- Keywords
- Major Depressive Disorder, Treatment Resistant Depression, Depression, Transcranial Magnetic Stimulation, TMS, Intermittent Theta Burst Stimulation, iTBS, Accelerated TMS, Accelerated iTBS, Dorsomedial Prefrontal Cortex, Biomarkers, Neuroinflammation, BDNF, Cortisol, ACTH
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Depression, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Accelerated Intermittent Theta Burst Stimulation (iTBS)Device
Accelerated intermittent theta burst stimulation (iTBS) is administered bilaterally to the dorsomedial prefrontal cortex using a double-cone coil, targeting the stimulation site based on anatomical landmarks. Treatment is delivered over five consecutive days with four sessions per day (total of 20 sessions). Each session consists of 600 pulses per hemisphere (1200 pulses total) at an intensity of 120% of the individual motor threshold. Participants with partial response may receive an additional 10 sessions.
| Study group | Role | What they receive |
|---|---|---|
| Accelerated iTBS | Experimental | Participants receive accelerated bilateral dorsomedial prefrontal cortex intermittent theta burst stimulation (iTBS) administered over five consecutive days, with four sessions per day (20 sessions total). Participants with partial clinical response may receive an additional 10 sessions. Receives: Device: Accelerated Intermittent Theta Burst Stimulation (iTBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hamilton Depression Rating Scale (HAM-D) Score
Change in depressive symptom severity measured by the 17-item Hamilton Depression Rating Scale (HAM-D-17). Scores range from 0 to 53, with higher scores indicating greater depression severity.
Measured: Baseline, within 3 days after completion of treatment and 1-month follow-up
Secondary outcomes (10)
Treatment Response Rate Based on HAM-D
Proportion of participants achieving ≥50% reduction in HAM-D score from baseline.
Measured: within 3 days after completion of treatment
Remission Rate Based on HAM-D
Proportion of participants achieving remission defined as HAM-D score ≤7.
Measured: Within 3 days after completion of treatment
Sustained Treatment Response at 1-Month Follow-Up
Proportion of participants maintaining ≥50% reduction in HAM-D score at 1-month follow-up.
Measured: 1 month after treatment completion
Sustained Remission at 1-Month Follow-Up
Proportion of participants maintaining remission, defined as HAM-D score ≤7, at 1-month follow-up.
Measured: 1 month after treatment completion
Change in Serum Cortisol and ACTH Levels
Change in serum cortisol and adrenocorticotropic hormone (ACTH) levels following treatment.
Measured: Baseline, within 3 days after completion of treatment and 1-month follow-up
Change in Serum BDNF Levels
Change in serum brain-derived neurotrophic factor (BDNF) levels following treatment.
Measured: Baseline, within 3 days after completion of treatment, and 1-month follow-up
Change in Inflammatory Biomarkers
Change in serum IL-1β, IL-6, TNF-α, and C-reactive protein (CRP) levels following treatment.
Measured: Baseline, within 3 days after completion of treatment, and 1-month follow-up
Change in Beck Depression Inventory (BDI) Score
Change in depressive symptom severity measured by the Beck Depression Inventory(BDI). Scores range from 0 to 63, with higher scores indicating greater depressive symptom severity.
Measured: Baseline, within 3 days after completion of treatment, and 1-month follow-up
Change in Beck Anxiety Inventory (BAI) Score
Change in anxiety symptom severity measured by the Beck Anxiety Inventory (BAI). Scores range from 0 to 63, with higher scores indicating greater anxiety severity.
Measured: Baseline, end of treatment, and 1-month follow-up
Change in Clinical Global Impression (CGI) Score
The scale includes three clinician-rated dimensions assessing illness severity (1-7), clinical improvement (1-7), and side effect severity (1-4).
Measured: Baseline, within 3 days after completion of treatment and 1-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2026
- Study start8 Mar 2026
- Primary completionDec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
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.
- 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
- Single-arm, open-label interventional study in which all participants receive accelerated bilateral dorsomedial prefrontal cortex intermittent theta burst stimulation
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istanbul University - Cerrahpasa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Merve Rana Altunel, Istanbul University - Cerrahpasa
- Investigators
- Cana Aksoy Poyraz, Prof. Dr., Study chair, Istanbul University - Cerrahpasa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07603804
- Sponsor's protocol ID
- E-24687260-604.01-1433619
- Other IDs
- TTU-2025-38714
- Acronym
- AIM-D
- Status last verified
- May 2026
- First submitted
- 30 Apr 2026
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be publicly shared due to institutional and ethical considerations.
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Relationship Between Changes in Neurobiological Biomarkers After Accelerated Transcranial Magnetic Stimulation Treatment and Treatment Response in Patients With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT07603804
- Acronym / sponsor ID
- AIM-D / E-24687260-604.01-1433619
- Keywords
- Major Depressive Disorder, Treatment Resistant Depression, Depression, Transcranial Magnetic Stimulation, TMS, Intermittent Theta Burst Stimulation, iTBS, Accelerated TMS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Istanbul University - CerrahpasaUniversity, hospital or other
- Study start
- 8 Mar 2026 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 22 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.
Major depressive disorder (MDD) is a common and disabling psychiatric condition, and many patients do not achieve adequate response to standard antidepressant treatments. Accelerated intermittent theta burst stimulation (iTBS) is a promising neuromodulation approach that may provide rapid antidepressant effects. This prospective interventional study aims to evaluate the clinical effectiveness of accelerated bilateral dorsomedial prefrontal cortex iTBS in patients with MDD and to investigate treatment-related changes in neurobiological biomarkers, including cortisol, ACTH, BDNF, IL-1β, IL-6, TNF-α, and CRP. Associations between biomarker changes and treatment response will also be examined.
Detailed description
Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric disorder. A substantial proportion of patients do not achieve sufficient improvement with conventional antidepressant treatments, resulting in treatment-resistant or difficult-to-treat depression. Noninvasive neuromodulation approaches such as transcranial magnetic stimulation (TMS) have emerged as effective alternatives for these patients. Accelerated intermittent theta burst stimulation (iTBS), delivered in multiple daily sessions over a short period, may provide faster clinical improvement compared with conventional protocols.
This prospective single-arm interventional study aims to evaluate the clinical efficacy and biological correlates of accelerated bilateral dorsomedial prefrontal cortex (DMPFC) iTBS in adults with MDD who have shown inadequate response to at least one adequate antidepressant treatment trial.
Participants aged 18 to 65 years will receive accelerated bilateral DMPFC iTBS for five consecutive days, with four sessions per day (20 total sessions). Participants demonstrating partial clinical improvement without remission after 20 sessions may receive an additional 10 sessions according to clinical evaluation.
Clinical assessments will be performed at baseline, during treatment, at the end of treatment, and at one-month follow-up. Outcome measures include Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory, Beck Anxiety Inventory, suicidal ideation measures, self-rated depressive symptom scales, and Clinical Global Impression ratings.
Blood samples will be collected at baseline and after treatment to evaluate neurobiological biomarkers, including cortisol, adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP).
The primary objective is to determine treatment response based on reduction in depressive symptom severity. Secondary objectives are to examine biomarker changes associated with treatment, identify predictors of response, and explore the relationship between early symptom improvement and final clinical outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm, open-label interventional study in which all participants receive accelerated bilateral dorsomedial prefrontal cortex intermittent theta burst stimulation
| Arm | Type | Receives |
|---|---|---|
| Accelerated iTBS | Experimental | Device: Accelerated Intermittent Theta Burst Stimulation (iTBS)Participants receive accelerated bilateral dorsomedial prefrontal cortex intermittent theta burst stimulation (iTBS) administered over five consecutive days, with four sessions per day (20 sessions total). Participants with partial clinical response may receive an additional 10 sessions. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age between 18 and 65 years
- Diagnosis of Major Depressive Disorder according to DSM-5 criteria
- Inadequate response to at least one adequate antidepressant treatment trial
- Hamilton Depression Rating Scale (HAM-D) score ≥14 at baseline
- Stable dose of antidepressant medication for at least 4 weeks prior to study entry
Key exclusion criteria (16 listed)
- History of bipolar disorder, schizophrenia, schizoaffective disorder, or psychotic depression
- Current substance use disorder
- Neurological disorders that may affect brain function (e.g., epilepsy, multiple sclerosis, dementia, Parkinson's disease)
- History of epileptic seizures
- Severe head trauma
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 Intermittent Theta Burst Stimulation (iTBS)Accelerated intermittent theta burst stimulation (iTBS) is administered bilaterally to the dorsomedial prefrontal cortex using a double-cone coil, targeting the stimulation site based on anatomical landmarks. Treatment is delivered over five consecutive days with four sessions per day (total of 20 sessions). Each session consists of 600 pulses per hemisphere (1200 pulses total) at an intensity of 120% of the individual motor threshold. Participants with partial response may receive an additional 10 sessions. | Device | Accelerated iTBS |
Primary outcome
Change in Hamilton Depression Rating Scale (HAM-D) Score
Time frame: Baseline, within 3 days after completion of treatment and 1-month follow-up
Change in depressive symptom severity measured by the 17-item Hamilton Depression Rating Scale (HAM-D-17). Scores range from 0 to 53, with higher scores indicating greater depression severity.
10 secondary outcomes
Treatment Response Rate Based on HAM-D
Time frame: within 3 days after completion of treatment
Remission Rate Based on HAM-D
Time frame: Within 3 days after completion of treatment
Sustained Treatment Response at 1-Month Follow-Up
Time frame: 1 month after treatment completion
Sustained Remission at 1-Month Follow-Up
Time frame: 1 month after treatment completion
Change in Serum Cortisol and ACTH Levels
Time frame: Baseline, within 3 days after completion of treatment and 1-month follow-up
Change in Serum BDNF Levels
Time frame: Baseline, within 3 days after completion of treatment, and 1-month follow-up
Change in Inflammatory Biomarkers
Time frame: Baseline, within 3 days after completion of treatment, and 1-month follow-up
Change in Beck Depression Inventory (BDI) Score
Time frame: Baseline, within 3 days after completion of treatment, and 1-month follow-up
Change in Beck Anxiety Inventory (BAI) Score
Time frame: Baseline, end of treatment, and 1-month follow-up
Change in Clinical Global Impression (CGI) Score
Time frame: Baseline, within 3 days after completion of treatment and 1-month follow-up
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 22 May 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be publicly shared due to institutional and ethical considerations.
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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.
Cana Aksoy Poyraz, Prof. Dr. study chair
Istanbul University - Cerrahpasa
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 Intermittent Theta Burst Stimulation (iTBS) in people with Major Depressive Disorder (MDD) and Treatment Resistant Depression (TRD), 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 6 inclusion and 16 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 22 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?
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 Merve Rana Altunel Ülkü, MD (+90 506 303 10 68, ranaltunel@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hamilton Depression Rating Scale (HAM-D) Score (time frame: Baseline, within 3 days after completion of treatment and 1-month follow-up). 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 22 May 2026.