Treatment-resistant Depression (TRD)TRD-BIOTMSNCT07673913
Relationship of Peripheral Inflammatory and Neuroprotective Biomarkers With Response to Intermittent Theta Burst Stimulation in Treatment-Resistant Depression
A study testing Intermittent Theta Burst Stimulation (iTBS) in people with Treatment-resistant Depression (TRD) and Major Depression, run by Gulhane Training and Research Hospital at 2 sites in Turkey (Türkiye).
Trial summary
Treatment-resistant depression (TRD) is a major clinical challenge affecting a substantial proportion of patients with major depressive disorder who do not adequately respond to conventional antidepressant treatments. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Treatment-resistant Depression (TRD), Major Depression
- What is being tested?
- Intermittent Theta Burst Stimulation (iTBS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesTurkey (Türkiye)
- Study dates
- 1 Sep 2026to 1 Sep 2027
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Treatment-Resistant Depression Group:
- Age between 18 and 55 years. Male or female participants. Diagnosis of Major Depressive Disorder according to DSM-5-TR criteria. Inadequate response to at least two antidepressant treatments administered at adequate doses and durations.
- Eligible for transcranial magnetic stimulation (TMS) treatment. Able and willing to provide written informed consent. Able to complete neuropsychological assessments. Able to attend study visits and complete the treatment protocol.
- Healthy Control Group:
- Age between 18 and 55 years. Male or female participants. No current DSM-5-TR psychiatric disorder. Able and willing to provide written informed consent. Able to complete neuropsychological assessments.
Who cannot join
- Schizophrenia, bipolar disorder, organic mental disorders, or other major psychiatric disorders.
- History of epilepsy, brain tumor, severe head trauma, or significant neurological disease.
- Any contraindication to TMS. Presence of intracranial metal implants, cardiac pacemakers, cochlear implants, or other incompatible implanted devices.
- Active infection. Autoimmune disease or chronic inflammatory disease. Electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation within the previous 5 years.
- Previous intravenous or intranasal ketamine treatment. Pregnancy or breastfeeding. Active alcohol or substance use disorder. Inability to comply with study procedures. Inability to tolerate the iTBS protocol. Withdrawal of informed consent at any stage of the study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)2 sites, 2 recruiting
- Not yet recruiting
Gulhane Training and Research Hospital
Ankara, Ankara, 06000
BEYAZIT GARİP, Principal Investigator, 03123044512, beyazitgarip@gmail.com
- Recruiting
Gulhane Training and Research Hospital
Ankara, 06000
Dr.Beyazıt Garip, 03122977975, beyazitgarip@gmail.com
About this study
Official title: Relationship Between Response to Transcranial Magnetic Stimulation and Peripheral Inflammatory and Neuroprotective Biomarkers in Patients With Treatment-Resistant Depression
Treatment-resistant depression (TRD) is a major clinical challenge affecting a substantial proportion of patients with major depressive disorder who do not adequately respond to conventional antidepressant treatments. Intermittent theta burst stimulation (iTBS), a non-invasive neuromodulation technique targeting the left dorsolateral prefrontal cortex, has emerged as an effective treatment option for these patients. However, the biological mechanisms underlying treatment response remain poorly understood.
This single-center, prospective, investigator-initiated clinical study aims to investigate the effects of iTBS on clinical symptoms, executive functions, and peripheral inflammatory and neuroprotective biomarkers in patients with treatment-resistant depression.
Read more
Fifty patients with treatment-resistant depression and fifty healthy control participants will be enrolled. Patients will receive active iTBS treatment for four weeks (20 sessions), while healthy controls will undergo baseline clinical, cognitive, and biological assessments without receiving any intervention.
Clinical outcomes will be evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Patient Health Questionnaire-9 (PHQ-9), Clinical Global Impression (CGI), and Insomnia Severity Index (ISI). Executive functions will be assessed using the Wisconsin Card Sorting Test, Trail Making Test A and B, and verbal fluency tests.
Peripheral blood samples will be collected before and after treatment to measure inflammatory, neuroplasticity, and neuroprotective biomarkers, including IL-1β, IL-6, IL-10, TNF-α, high-sensitivity C-reactive protein (hs-CRP), brain-derived neurotrophic factor (BDNF), apolipoprotein D (APOD), serum amyloid A1 (SAA1), and serum amyloid A2 (SAA2). Gene expression analyses will also be performed using quantitative polymerase chain reaction (qPCR).
The study aims to identify biological mechanisms associated with iTBS treatment response and to explore potential biomarkers that may predict clinical improvement in patients with treatment-resistant depression. The findings may contribute to the development of personalized neuromodulation strategies and biomarker-guided treatment approaches for depression.
Read the detailed description
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder associated with substantial functional impairment, reduced quality of life, increased suicide risk, and significant socioeconomic burden. Despite the availability of pharmacological, psychotherapeutic, and neuromodulation-based treatments, a considerable proportion of patients fail to achieve adequate clinical improvement and develop treatment-resistant depression (TRD).
Treatment-resistant depression is commonly defined as inadequate response to at least two antidepressant medications administered at adequate doses and durations. Patients with TRD frequently experience chronic symptoms, recurrent episodes, impaired psychosocial functioning, increased healthcare utilization, and poorer long-term outcomes.
Intermittent theta burst stimulation (iTBS) has emerged as an effective, non-invasive neuromodulation treatment for TRD. Compared with conventional high-frequency repetitive transcranial magnetic stimulation (rTMS), iTBS offers substantially shorter treatment sessions while maintaining comparable efficacy. However, the biological mechanisms underlying treatment response remain incompletely understood, and reliable biomarkers predicting therapeutic outcomes have not yet been established.
Accumulating evidence suggests that neuroinflammation, impaired neuroplasticity, oxidative stress, and altered immune regulation contribute to the pathophysiology of depression and may influence treatment response. Therefore, investigating biological changes associated with iTBS may improve the understanding of therapeutic mechanisms and facilitate the development of personalized treatment strategies.
This single-center, prospective, investigator-initiated clinical study aims to comprehensively evaluate clinical outcomes, executive functions, and peripheral inflammatory and neuroprotective biomarkers in patients with TRD receiving iTBS treatment.
A total of 100 participants will be enrolled, including 50 patients with treatment-resistant depression and 50 healthy controls. Patients will receive active iTBS over the left dorsolateral prefrontal cortex using a MagVenture X100 device for 20 sessions administered over four weeks. Healthy controls will not receive any intervention and will participate only in baseline assessments.
Clinical outcomes will be evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Patient Health Questionnaire-9 (PHQ-9), Clinical Global Impression (CGI), and Insomnia Severity Index (ISI). Executive functions will be assessed using the Wisconsin Card Sorting Test (WCST), Trail Making Test A and B (TMT-A and TMT-B), and verbal fluency tests.
Peripheral blood samples will be collected before and after treatment. Serum levels of IL-1β, IL-6, IL-10, TNF-α, high-sensitivity C-reactive protein (hs-CRP), brain-derived neurotrophic factor (BDNF), apolipoprotein D (APOD), serum amyloid A1 (SAA1), and serum amyloid A2 (SAA2) will be measured using enzyme-linked immunosorbent assays (ELISA). Gene expression analyses of relevant biomarkers will be performed using quantitative polymerase chain reaction (qPCR).
The primary outcome will be the change in HAM-D-17 scores from baseline to week 4. Secondary outcomes will include changes in clinical scales, executive function performance, biomarker levels, and gene expression profiles. Associations between biological markers, cognitive performance, and treatment response will also be examined.
The study seeks to identify potential biomarker signatures associated with iTBS response and contribute to the development of biomarker-guided, personalized neuromodulation strategies for treatment-resistant depression.
- Being tested
- Intermittent Theta Burst Stimulation (iTBS)
- Keywords
- Treatment-Resistant Depression, Transcranial Magnetic Stimulation, Biomarkers, Personalized Psychiatry, Neuromodulation
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent Theta Burst Stimulation (iTBS)Device
Intermittent theta burst stimulation (iTBS) will be administered over the left dorsolateral prefrontal cortex using a CE-marked MagVenture X100 transcranial magnetic stimulation device. Stimulation intensity will be set at 90% of each participant's resting motor threshold. The protocol will consist of bursts of three pulses delivered at 50 Hz, repeated at a frequency of 5 Hz, with 2-second stimulation trains followed by 8-second intertrain intervals. Participants will receive 1800 pulses per session, five sessions per week, for a total of 20 sessions over four weeks (36,000 pulses in total). Participants will continue their routine pharmacological treatments throughout the study, and no investigational medicinal products will be initiated as part of the research protocol.
| Study group | Role | What they receive |
|---|---|---|
| Active iTBS Treatment | Experimental | Participants with treatment-resistant depression will receive active intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex using a MagVenture X100 device. Treatment will be administered at 90% of the resting motor threshold, with 1800 pulses per session, 5 sessions per week, for a total of 20 sessions over 4 weeks. Participants will continue their routine pharmacological treatments throughout the study. Clinical assessments, neuropsychological testing, and peripheral biomarker analyses will be performed before and after treatment. Receives: Device: 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-17) Total Score
The primary outcome is the change in the 17-item Hamilton Depression Rating Scale (HAM-D-17) total score between baseline and week 4 following intermittent theta burst stimulation (iTBS) treatment. Clinical response will be defined as a reduction of 50% or greater from baseline, and remission will be defined as a HAM-D-17 total score of 7 or lower.
Measured: Baseline and Week 4
Secondary outcomes (6)
Change in Patient Health Questionnaire-9 (PHQ-9) Score
Change in depressive symptom severity measured by the Patient Health Questionnaire-9 (PHQ-9) following iTBS treatment.
Measured: Baseline and Week 4
Change in Insomnia Severity Index (ISI) Score
Change in insomnia severity following iTBS treatment.
Measured: Baseline and Week 4
Change in Wisconsin Card Sorting Test Performance
Change in executive function performance assessed using the Wisconsin Card Sorting Test
Measured: Baseline and Week 4
Change in Peripheral Inflammatory Biomarker Levels
Change in IL-1β, IL-6, IL-10, TNF-α, and high-sensitivity C-reactive protein (hs-CRP) levels following iTBS treatment.
Measured: Baseline and Week 4
Change in Neuroprotective Biomarker Levels
Change in BDNF, APOD, SAA1, and SAA2 levels following iTBS treatment
Measured: Baseline and Week 4
Change in Gene Expression Profiles
Change in gene expression levels of inflammatory and neuroprotective biomarkers measured by quantitative polymerase chain reaction (qPCR).
Measured: Baseline and Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Sep 2027 (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 Treatment-resistant Depression (TRD)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
- Participants with treatment-resistant depression will receive active intermittent theta burst stimulation (iTBS) administered over the left dorsolateral prefrontal cortex for 20 sessions during a 4-week treatment period. Healthy control participants will not receive any intervention and will undergo baseline clinical, cognitive, and biological assessments for comparative analyses.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gulhane Training and Research Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Beyazit Garip, Gulhane Training and Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07673913
- Sponsor's protocol ID
- GULHANE-TRD-TMS-BIOMARKER-2026
- Acronym
- TRD-BIOTMS
- Status last verified
- Sep 2026
- First submitted
- 23 Jun 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) underlying the published results will be made available to qualified researchers upon reasonable request after publication of the primary study results. Data sharing will be subject to institutional approval and applicable ethical and legal regulations to protect participant confidentiality.
Publications
Fyfe-Desmarais G, Desmarais F, Rassart E, Mounier C. Apolipoprotein D in Oxidative Stress and Inflammation. Antioxidants (Basel). 2023 Apr 28;12(5):1027. doi: 10.3390/antiox12051027.
PubMed 37237893Lee H, Rhee SJ, Kim J, Lee Y, Kim H, Lee J, Lee K, Shin H, Kim H, Lee TY, Kim M, Kim EY, Kim SH, Ahn YM, Kwon JS, Han D, Ha K. Plasma proteomic data in bipolar II disorders and major depressive disorders. Data Brief. 2021 Oct 17;39:107495. doi: 10.1016/j.dib.2021.107495. eCollection 2021 Dec.
PubMed 34825021Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimul. 2016 May-Jun;9(3):336-346. doi: 10.1016/j.brs.2016.03.010. Epub 2016 Mar 16.
PubMed 27090022Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.
PubMed 29726344
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relationship Between Response to Transcranial Magnetic Stimulation and Peripheral Inflammatory and Neuroprotective Biomarkers in Patients With Treatment-Resistant Depression
- ClinicalTrials.gov ID
- NCT07673913
- Acronym / sponsor ID
- TRD-BIOTMS / GULHANE-TRD-TMS-BIOMARKER-2026
- Keywords
- Treatment-Resistant Depression, Transcranial Magnetic Stimulation, Biomarkers, Personalized Psychiatry, Neuromodulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Gulhane Training and Research HospitalOther government
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 29 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.
Treatment-resistant depression (TRD) is a major clinical challenge affecting a substantial proportion of patients with major depressive disorder who do not adequately respond to conventional antidepressant treatments. Intermittent theta burst stimulation (iTBS), a non-invasive neuromodulation technique targeting the left dorsolateral prefrontal cortex, has emerged as an effective treatment option for these patients. However, the biological mechanisms underlying treatment response remain poorly understood.
This single-center, prospective, investigator-initiated clinical study aims to investigate the effects of iTBS on clinical symptoms, executive functions, and peripheral inflammatory and neuroprotective biomarkers in patients with treatment-resistant depression.
Fifty patients with treatment-resistant depression and fifty healthy control participants will be enrolled. Patients will receive active iTBS treatment for four weeks (20 sessions), while healthy controls will undergo baseline clinical, cognitive, and biological assessments without receiving any intervention.
Clinical outcomes will be evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Patient Health Questionnaire-9 (PHQ-9), Clinical Global Impression (CGI), and Insomnia Severity Index (ISI). Executive functions will be assessed using the Wisconsin Card Sorting Test, Trail Making Test A and B, and verbal fluency tests.
Peripheral blood samples will be collected before and after treatment to measure inflammatory, neuroplasticity, and neuroprotective biomarkers, including IL-1β, IL-6, IL-10, TNF-α, high-sensitivity C-reactive protein (hs-CRP), brain-derived neurotrophic factor (BDNF), apolipoprotein D (APOD), serum amyloid A1 (SAA1), and serum amyloid A2 (SAA2). Gene expression analyses will also be performed using quantitative polymerase chain reaction (qPCR).
The study aims to identify biological mechanisms associated with iTBS treatment response and to explore potential biomarkers that may predict clinical improvement in patients with treatment-resistant depression. The findings may contribute to the development of personalized neuromodulation strategies and biomarker-guided treatment approaches for depression.
Detailed description
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder associated with substantial functional impairment, reduced quality of life, increased suicide risk, and significant socioeconomic burden. Despite the availability of pharmacological, psychotherapeutic, and neuromodulation-based treatments, a considerable proportion of patients fail to achieve adequate clinical improvement and develop treatment-resistant depression (TRD).
Treatment-resistant depression is commonly defined as inadequate response to at least two antidepressant medications administered at adequate doses and durations. Patients with TRD frequently experience chronic symptoms, recurrent episodes, impaired psychosocial functioning, increased healthcare utilization, and poorer long-term outcomes.
Intermittent theta burst stimulation (iTBS) has emerged as an effective, non-invasive neuromodulation treatment for TRD. Compared with conventional high-frequency repetitive transcranial magnetic stimulation (rTMS), iTBS offers substantially shorter treatment sessions while maintaining comparable efficacy. However, the biological mechanisms underlying treatment response remain incompletely understood, and reliable biomarkers predicting therapeutic outcomes have not yet been established.
Accumulating evidence suggests that neuroinflammation, impaired neuroplasticity, oxidative stress, and altered immune regulation contribute to the pathophysiology of depression and may influence treatment response. Therefore, investigating biological changes associated with iTBS may improve the understanding of therapeutic mechanisms and facilitate the development of personalized treatment strategies.
This single-center, prospective, investigator-initiated clinical study aims to comprehensively evaluate clinical outcomes, executive functions, and peripheral inflammatory and neuroprotective biomarkers in patients with TRD receiving iTBS treatment.
A total of 100 participants will be enrolled, including 50 patients with treatment-resistant depression and 50 healthy controls. Patients will receive active iTBS over the left dorsolateral prefrontal cortex using a MagVenture X100 device for 20 sessions administered over four weeks. Healthy controls will not receive any intervention and will participate only in baseline assessments.
Clinical outcomes will be evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Patient Health Questionnaire-9 (PHQ-9), Clinical Global Impression (CGI), and Insomnia Severity Index (ISI). Executive functions will be assessed using the Wisconsin Card Sorting Test (WCST), Trail Making Test A and B (TMT-A and TMT-B), and verbal fluency tests.
Peripheral blood samples will be collected before and after treatment. Serum levels of IL-1β, IL-6, IL-10, TNF-α, high-sensitivity C-reactive protein (hs-CRP), brain-derived neurotrophic factor (BDNF), apolipoprotein D (APOD), serum amyloid A1 (SAA1), and serum amyloid A2 (SAA2) will be measured using enzyme-linked immunosorbent assays (ELISA). Gene expression analyses of relevant biomarkers will be performed using quantitative polymerase chain reaction (qPCR).
The primary outcome will be the change in HAM-D-17 scores from baseline to week 4. Secondary outcomes will include changes in clinical scales, executive function performance, biomarker levels, and gene expression profiles. Associations between biological markers, cognitive performance, and treatment response will also be examined.
The study seeks to identify potential biomarker signatures associated with iTBS response and contribute to the development of biomarker-guided, personalized neuromodulation strategies for treatment-resistant depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants with treatment-resistant depression will receive active intermittent theta burst stimulation (iTBS) administered over the left dorsolateral prefrontal cortex for 20 sessions during a 4-week treatment period. Healthy control participants will not receive any intervention and will undergo baseline clinical, cognitive, and biological assessments for comparative analyses.
| Arm | Type | Receives |
|---|---|---|
| Active iTBS Treatment | Experimental | Device: Intermittent Theta Burst Stimulation (iTBS)Participants with treatment-resistant depression will receive active intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex using a MagVenture X100 device. Treatment will be administered at 90% of the resting motor threshold, with 1800 pulses per session, 5 sessions per week, for a total of 20 sessions over 4 weeks. Participants will continue their routine pharmacological treatments throughout the study. Clinical assessments, neuropsychological testing, and peripheral biomarker analyses will be performed before and after treatment. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age between 18 and 55 years. Male or female participants. Diagnosis of Major Depressive Disorder according to DSM-5-TR criteria. Inadequate response to at least two antidepressant treatments administered at adequate doses and durations.
- Eligible for transcranial magnetic stimulation (TMS) treatment. Able and willing to provide written informed consent. Able to complete neuropsychological assessments. Able to attend study visits and complete the treatment protocol.
- Age between 18 and 55 years. Male or female participants. No current DSM-5-TR psychiatric disorder. Able and willing to provide written informed consent. Able to complete neuropsychological assessments.
Key exclusion criteria (5 listed)
- Schizophrenia, bipolar disorder, organic mental disorders, or other major psychiatric disorders.
- History of epilepsy, brain tumor, severe head trauma, or significant neurological disease.
- Any contraindication to TMS. Presence of intracranial metal implants, cardiac pacemakers, cochlear implants, or other incompatible implanted devices.
- Active infection. Autoimmune disease or chronic inflammatory disease. Electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation within the previous 5 years.
- Previous intravenous or intranasal ketamine treatment. Pregnancy or breastfeeding. Active alcohol or substance use disorder. Inability to comply with study procedures. Inability to tolerate the iTBS protocol. Withdrawal of informed consent at any stage of the study.
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 |
|---|---|---|
| Intermittent Theta Burst Stimulation (iTBS)Intermittent theta burst stimulation (iTBS) will be administered over the left dorsolateral prefrontal cortex using a CE-marked MagVenture X100 transcranial magnetic stimulation device. Stimulation intensity will be set at 90% of each participant's resting motor threshold. The protocol will consist of bursts of three pulses delivered at 50 Hz, repeated at a frequency of 5 Hz, with 2-second stimulation trains followed by 8-second intertrain intervals. Participants will receive 1800 pulses per session, five sessions per week, for a total of 20 sessions over four weeks (36,000 pulses in total). Participants will continue their routine pharmacological treatments throughout the study, and no investigational medicinal products will be initiated as part of the research protocol. | Device | Active iTBS Treatment |
Primary outcome
Change in Hamilton Depression Rating Scale (HAM-D-17) Total Score
Time frame: Baseline and Week 4
The primary outcome is the change in the 17-item Hamilton Depression Rating Scale (HAM-D-17) total score between baseline and week 4 following intermittent theta burst stimulation (iTBS) treatment. Clinical response will be defined as a reduction of 50% or greater from baseline, and remission will be defined as a HAM-D-17 total score of 7 or lower.
6 secondary outcomes
Change in Patient Health Questionnaire-9 (PHQ-9) Score
Time frame: Baseline and Week 4
Change in Insomnia Severity Index (ISI) Score
Time frame: Baseline and Week 4
Change in Wisconsin Card Sorting Test Performance
Time frame: Baseline and Week 4
Change in Peripheral Inflammatory Biomarker Levels
Time frame: Baseline and Week 4
Change in Neuroprotective Biomarker Levels
Time frame: Baseline and Week 4
Change in Gene Expression Profiles
Time frame: Baseline and Week 4
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 14 Sep 2026.
- Background: PubMed 37237893Fyfe-Desmarais G, Desmarais F, Rassart E, Mounier C. Apolipoprotein D in Oxidative Stress and Inflammation. Antioxidants (Basel). 2023 Apr 28;12(5):1027. doi: 10.3390/antiox12051027.
- Background: PubMed 34825021Lee H, Rhee SJ, Kim J, Lee Y, Kim H, Lee J, Lee K, Shin H, Kim H, Lee TY, Kim M, Kim EY, Kim SH, Ahn YM, Kwon JS, Han D, Ha K. Plasma proteomic data in bipolar II disorders and major depressive disorders. Data Brief. 2021 Oct 17;39:107495. doi: 10.1016/j.dib.2021.107495. eCollection 2021 Dec.
- Background: PubMed 27090022Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimul. 2016 May-Jun;9(3):336-346. doi: 10.1016/j.brs.2016.03.010. Epub 2016 Mar 16.
- Background: PubMed 29726344Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) underlying the published results will be made available to qualified researchers upon reasonable request after publication of the primary study results. Data sharing will be subject to institutional approval and applicable ethical and legal regulations to protect participant confidentiality.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intermittent Theta Burst Stimulation (iTBS) in people with Treatment-resistant Depression (TRD) and Major Depression, run by Gulhane Training and Research Hospital at 2 sites 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 5 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 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 BEYAZIT GARİP, Principal Investigator (+903123044512, beyazitgarip@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-17) Total Score (time frame: Baseline and Week 4). 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 NCT07673913, 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 14 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.