Major Depression DisorderPROMET_TMSNCT07039370
Molecular Signatures of TMS Response in Treatment-Resistant Depression
A study testing TMS in people with Major Depression Disorder, run by Gulhane Training and Research Hospital at 2 sites in Turkey (Türkiye).
Trial summary
Transcranial Magnetic Stimulation (TMS) therapy is an approved and effective treatment option for treatment-resistant depression (TRD). This study aims to identify biomarkers that predict TMS treatment response in TRD, provide insights into the neurobiological mechanisms underlying TMS efficacy, and contribute to… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depression Disorder
- What is being tested?
- TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 2 sitesTurkey (Türkiye)
- Study dates
- 15 Jun 2025to 1 Jun 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Diagnosis of Major Depressive Disorder (MDD) according to DSM-5-TR criteria.
- Inadequate clinical response to at least two different antidepressants and/or anti-obsessive agents administered at therapeutic doses and durations.
- Clinical symptoms not better explained by metabolic or organic medical conditions.
- No epileptic activity detected on routine electroencephalography (EEG) prior to TMS initiation.
- Routine pre-TMS laboratory tests reveal no abnormalities that may significantly affect treatment response, including:
- Normal thyroid hormone profile
Show all 11Show fewer
- No significant vitamin deficiencies
- No markedly elevated inflammatory markers
- No history or current evidence of hearing loss on clinical evaluation; if present, evaluation by an otolaryngologist will be obtained.
- Age 18 years and older.
- Ability to provide written informed consent.
Who cannot join
- Any contraindication to TMS as identified in the standardized pre-TMS risk assessment form.
- Presence of epileptic focus detected on pre-TMS EEG.
- History of significant head trauma, loss of consciousness, or intracranial surgery.
- Presence of metal implants or foreign bodies incompatible with TMS (e.g., aneurysm clips, surgical clamps, metallic fragments).
- Abnormal thyroid hormone levels in pre-TMS laboratory testing.
- Significantly elevated inflammation markers (e.g., CRP) in pre-TMS bloodwork.
Show all 13Show fewer
- Vitamin deficiencies associated with cognitive impairment (e.g., B12, folate) in pre-TMS labs.
- Electrolyte imbalances on pre-TMS blood testing.
- History of psychotic disorder or bipolar I/II disorder.
- History of substance-induced psychosis or bipolar disorder.
- Current or past substance use disorder (including alcohol, stimulants, or illicit drugs), unless abstinent from substances (excluding alcohol) for a minimum of 12 months.
- Voluntary discontinuation of TMS during the treatment course.
- Any serious adverse event or unexpected clinical condition during treatment that necessitates discontinuation of TMS.
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
- Recruiting
Gulhane Training and Research Hospital
Ankara, Ankara, 06000
BEYAZIT GARİP, Medical Doctor, +903123044512, beyazitgarip@gmail.com
- Recruiting
Gulhane Training and Research Hospital
Ankara, Ankara, 06300
BEYAZIT GARİP, Principal Investigator, +905309731105, beyazitgarip@gmail.com
About this study
Official title: The Relationship Between Plasma Metabolomics and Proteomics Profiling and Response to Transcranial Magnetic Stimulation Therapy in Treatment-Resistant Depression
Transcranial Magnetic Stimulation (TMS) therapy is an approved and effective treatment option for treatment-resistant depression (TRD). This study aims to identify biomarkers that predict TMS treatment response in TRD, provide insights into the neurobiological mechanisms underlying TMS efficacy, and contribute to personalized treatment strategies. By establishing proteomic and metabolomic signatures, this research seeks to enhance clinical decision-making, reduce healthcare costs, and improve patient outcomes in TRD. The findings will align with the precision medicine movement in psychiatry, advancing biomarker-driven therapeutic approaches for treatment-resistant depression.
Read the detailed description
This prospective cohort study aims to investigate the relationship between plasma proteomic and metabolomic profiles and the treatment response to transcranial magnetic stimulation (TMS) in patients with treatment-resistant depression (TRD). TRD is defined as a subtype of major depressive disorder (MDD), characterized by an inadequate response to at least two adequate trials of antidepressant therapy. Despite the clinical efficacy of TMS as a non-invasive neuromodulation treatment, the biological underpinnings that determine patient responsiveness remain unclear. This study addresses that gap by evaluating blood-based molecular biomarkers that may predict or reflect TMS treatment outcomes.
A total of 55 TRD patients, diagnosed according to DSM-5-TR criteria and confirmed through the SCID-5 structured clinical interview, will be enrolled. An additional 55 healthy individuals matched for age and sex will serve as a control group for baseline plasma comparisons. Patients will undergo a standardized TMS protocol using the MagVenture™ X100™ device. The protocol includes 20 treatment sessions over four weeks, with each session delivering 1,800 pulses of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC). Motor threshold will be assessed weekly to calibrate treatment intensity to 90% of the resting motor threshold.
Blood samples will be collected from TRD patients prior to the first TMS session and after the 20th session, while healthy controls will provide samples at a single time point. Proteomic analysis will be conducted using LC-MS/MS following protein extraction, digestion, and purification. Metabolomic profiling will be carried out using LC-MS coupled with ion mobility spectrometry, enabling the identification of a wide range of plasma metabolites.
Psychiatric assessments, including the Hamilton Depression Rating Scale (HAM-D), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and the Clinical Global Impression (CGI) scale, will be administered at baseline and post-treatment to monitor clinical outcomes. Data integration and bioinformatics analyses will be performed using MaxQuant, Perseus, and MetaboAnalyst 6.0, enabling the identification of differentially expressed proteins and metabolites associated with treatment response.
The primary objective of the study is to determine whether plasma proteomic and metabolomic profiles differ significantly between TMS responders and non-responders. Secondary objectives include identifying predictive biomarkers for TMS efficacy and assessing biological changes correlated with clinical improvement.
Primary outcomes will focus on identifying molecular signatures that correlate with treatment responsiveness. Secondary outcomes will include changes in depression severity scores, documentation of any adverse effects related to TMS, and examination of correlations between biomarker expression and pharmacological history.
This study is crucial for advancing personalized treatment approaches in psychiatry. By identifying objective, blood-based biomarkers of TMS response, it may become possible to tailor treatment strategies, reduce unnecessary interventions, and improve therapeutic outcomes for individuals suffering from TRD.
- Conditions
- Major Depression Disorder
- Being tested
- TMS
- Keywords
- TMS, Metabolomics, Proteomics, Treatment Resistance, Molecular Signuture
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique approved for the treatment of major depressive disorder (MDD), particularly in individuals with treatment-resistant depression (TRD). TMS targets the left dorsolateral prefrontal cortex (DLPFC), a brain region often underactive in depression, and modulates neural activity through magnetic pulses.
This study aims to evaluate the effects of TMS on plasma proteomic and metabolomic profiles in patients with TRD. Participants will undergo 20 sessions of intermittent theta burst stimulation (iTBS) over four weeks. Blood samples will be collected before and after treatment to identify molecular changes associated with clinical response. Healthy controls will provide single-time-point blood samples for baseline comparison. Findings may support the development of biomarker-based strategies for personalized treatment in psychiatry.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial Magnetic Stimualtion Treatment Arm | Experimental | This arm includes participants diagnosed with treatment-resistant depression (TRD) who will receive transcranial magnetic stimulation (TMS) therapy. TMS will be delivered using the MagVenture™ X100™ device. The treatment protocol consists of 20 sessions over a 4-week period (5 sessions per week). Stimulation will target the left dorsolateral prefrontal cortex (DLPFC) using intermittent theta burst stimulation (iTBS). Motor threshold will be determined at baseline and reassessed weekly to calibrate stimulation intensity at 90% of the resting motor threshold.
Blood samples will be collected from participants at two time points: prior to the first TMS session (pre-treatment) and following the final (20th) session (post-treatment). Proteomic and metabolomic analyses will be performed using high-resolution liquid chromatography-mass spectrometry (LC-MS). The goal is to identify differentially expressed proteins and metabolites associated with clinical response to TMS. Receives: Device: TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Proteomic Profile Changes After TMS in Patients with Treatment-Resistant Depression
Assessment of differences in plasma proteomic profiles in treatment-resistant depression (TRD) patients before and after transcranial magnetic stimulation (TMS), using high-resolution liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Changes in protein expression will be used to identify potential biomarkers of treatment response.
Measured: From enrollment to end of treatment at 4 weeks
Plasma Metabolomic Profile Changes After TMS in Patients with Treatment-Resistant Depression
Evaluation of global metabolomic changes in plasma of TRD patients pre- and post-TMS therapy. Analysis will be conducted via liquid chromatography-mass spectrometry with ion mobility separation (LC-TIMS-TOF-MS), enabling identification of differential metabolites associated with clinical outcomes.
Measured: From enrollment to end of treatment at 4 weeks
Fold Change in Baseline Proteomic Markers Between Treatment Responders and Non-Responders
Differences in baseline proteomic markers between treatment responders and non-responders will be assessed using LC-MS/MS. Fold change values will be calculated to identify proteins with significant differential expression between the two groups.
Measured: From enrollment to end of the treatment at 4 weeks
Variable Importance in Projection Scores of Predictive Proteins
Variable Importance in Projection scores will be calculated using multivariate statistical analysis (e.g., PLS-DA) to rank the importance of baseline proteomic markers in distinguishing treatment responders from non-responders.
Measured: Baseline and End of 4-week treatment
Area Under the ROC Curve for Predictive Proteomic Markers Between Treatment Responders and Non-Responders
Receiver Operating Characteristic (ROC) curve analysis will be performed to evaluate the predictive performance of baseline and end-of-treatment proteomic markers in distinguishing treatment responders from non-responders. Area Under the Curve (AUC) values will be calculated to assess discriminative ability.
Measured: Baseline and End of 4-week treatment
Fold Change in Baseline Plasma Metabolomic Markers Between TMS Responders and Non-Responders
Fold change in baseline plasma metabolomic expression levels will be assessed between TMS treatment responders and non-responders using LC-MS/MS. The analysis aims to identify significantly altered metabolites that may predict treatment response.
Measured: Baseline
Variable Importance in Projection Scores of Baseline Plasma Metabolomic Markers Between TMS Responders and Non-Responders
Variable Importance in Projection scores will be calculated using multivariate statistical models (e.g., PLS-DA) to rank baseline plasma metabolomic markers according to their importance in differentiating TMS treatment responders from non-responders.
Unitless
Measured: Baseline and End of 4-week treatment
Area Under the ROC Curve of Baseline Plasma Metabolomic Markers Between TMS Responders and Non-Responders
Receiver Operating Characteristic curve analysis will be conducted to evaluate the predictive accuracy of baseline plasma metabolomic markers in distinguishing TMS treatment responders from non-responders. The Area Under Curve (AUC)will quantify each marker's discriminative ability. Measurement Tool:
ROC curve analysis
Unit of Measure: AUC (0-1 scale)
Measured: Baseline and End of 4-week treatment
Secondary outcomes (6)
Change in Depression Severity Based on Hamilton Depression Rating Scale (HAM-D, 17-item)
Depression severity will be assessed using the 17-item clinician-administered HAM-D scale. Scores range from 0 to 34, with higher scores indicating more severe depressive symptoms. A clinical response is defined as a ≥50% reduction in HAM-D total score from baseline to post-treatment
Measured: From enrollment to the end of the treatment at 4 weeks
Change in Depression Severity Based on Patient Health Questionnaire-9 (PHQ-9)
Depression severity will be self-assessed by participants using the PHQ-9 scale. Scores range from 0 to 27, with higher scores reflecting more severe symptoms. A clinical response is defined as a ≥50% reduction in PHQ-9 total score from baseline to post-treatment.
Measured: From enrollment to the end of the treatment at 4 weeks
Change in Subjective Sleep Quality Measured by Pittsburgh Sleep Quality Index [Sleep Quality]
Subjective sleep quality will be assessed using the Pittsburgh Sleep Quality Index(PSQI) a self-reported questionnaire consisting of 24 items that evaluate sleep quality over the past month across seven domains (e.g., sleep latency, duration, disturbances). Total score range: 0 to 21. Minimum possible score: 0 (indicating good sleep quality). Maximum possible score: 21 (indicating poor sleep quality). Interpretation: Higher scores indicate worse sleep quality. Changes in PSQI total scores from baseline to the end of the 4-week treatment period will be analyzed.
Measured: From enrollment to end of the treatment 4 weeks
Correlation Between Antidepressant Medication Use and Clinical Response to TMS Measured by Hamilton Depression Rating Scale-17
This outcome will assess the correlation between concurrent antidepressant medication use and clinical response to Transcranial Magnetic Stimulation (TMS). Medication data collected: Drug name, dosage, duration. Clinical outcome: Change in Hamilton Depression Rating Scale-17 (HAM-D17) total score from baseline to end of treatment. Statistical method: Pearson or Spearman correlation (based on data distribution). Unit of Measure (Antidepressant Use): Continuous (daily dose in mg), duration in weeks. Unit of Measure (TMS Response): Change in HAM-D17 total score
Measured: From enrollment to end of the treatment at 4 weeks
Change in Headache and Scalp Pain Severity Measured by Visual Analog Scale (VAS) [Tolerability]
Change in Headache and Scalp Pain Severity Measured by Visual Analog Scale (VAS) [Tolerability]
Measured: Baseline and End of 4-week treatment
Incidence of Seizure Events
The number and percentage of participants who experience seizures during the 4-week treatment period will be recorded. Events will be classified according to severity and assessed for their relationship to the study intervention.
Measured: From enrollment to end of the 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2025
- Study start15 Jun 2025
- Primary completion15 Dec 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depression DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a prospective, single-group, open-label cohort study designed to evaluate the association between plasma proteomic and metabolomic profiles and clinical response to transcranial magnetic stimulation (TMS) in patients with treatment-resistant depression (TRD). All participants in the intervention arm will receive a standardized TMS protocol targeting the left dorsolateral prefrontal cortex. A group of age- and sex-matched healthy individuals will serve as a non-randomized control group for baseline biomarker comparison. No randomization or blinding will be employed.
- Masking
- None (open label)
- Enrolment
- 55 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
- NCT07039370
- Sponsor's protocol ID
- 2025/245 / 46418926
- Acronym
- PROMET_TMS
- Status last verified
- Sep 2026
- First submitted
- 31 May 2025
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual Participant Data (IDP) will be shared together with the Clinical Study Report
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relationship Between Plasma Metabolomics and Proteomics Profiling and Response to Transcranial Magnetic Stimulation Therapy in Treatment-Resistant Depression
- ClinicalTrials.gov ID
- NCT07039370
- Acronym / sponsor ID
- PROMET_TMS / 2025/245 / 46418926
- Conditions
- Major Depression Disorder
- Keywords
- TMS, Metabolomics, Proteomics, Treatment Resistance, Molecular Signuture
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Gulhane Training and Research HospitalOther government
- Study start
- 15 Jun 2025 (actual)
- Primary completion
- 15 Dec 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 26 Jun 2025 (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.
Transcranial Magnetic Stimulation (TMS) therapy is an approved and effective treatment option for treatment-resistant depression (TRD). This study aims to identify biomarkers that predict TMS treatment response in TRD, provide insights into the neurobiological mechanisms underlying TMS efficacy, and contribute to personalized treatment strategies. By establishing proteomic and metabolomic signatures, this research seeks to enhance clinical decision-making, reduce healthcare costs, and improve patient outcomes in TRD. The findings will align with the precision medicine movement in psychiatry, advancing biomarker-driven therapeutic approaches for treatment-resistant depression.
Detailed description
This prospective cohort study aims to investigate the relationship between plasma proteomic and metabolomic profiles and the treatment response to transcranial magnetic stimulation (TMS) in patients with treatment-resistant depression (TRD). TRD is defined as a subtype of major depressive disorder (MDD), characterized by an inadequate response to at least two adequate trials of antidepressant therapy. Despite the clinical efficacy of TMS as a non-invasive neuromodulation treatment, the biological underpinnings that determine patient responsiveness remain unclear. This study addresses that gap by evaluating blood-based molecular biomarkers that may predict or reflect TMS treatment outcomes.
A total of 55 TRD patients, diagnosed according to DSM-5-TR criteria and confirmed through the SCID-5 structured clinical interview, will be enrolled. An additional 55 healthy individuals matched for age and sex will serve as a control group for baseline plasma comparisons. Patients will undergo a standardized TMS protocol using the MagVenture™ X100™ device. The protocol includes 20 treatment sessions over four weeks, with each session delivering 1,800 pulses of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC). Motor threshold will be assessed weekly to calibrate treatment intensity to 90% of the resting motor threshold.
Blood samples will be collected from TRD patients prior to the first TMS session and after the 20th session, while healthy controls will provide samples at a single time point. Proteomic analysis will be conducted using LC-MS/MS following protein extraction, digestion, and purification. Metabolomic profiling will be carried out using LC-MS coupled with ion mobility spectrometry, enabling the identification of a wide range of plasma metabolites.
Psychiatric assessments, including the Hamilton Depression Rating Scale (HAM-D), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and the Clinical Global Impression (CGI) scale, will be administered at baseline and post-treatment to monitor clinical outcomes. Data integration and bioinformatics analyses will be performed using MaxQuant, Perseus, and MetaboAnalyst 6.0, enabling the identification of differentially expressed proteins and metabolites associated with treatment response.
The primary objective of the study is to determine whether plasma proteomic and metabolomic profiles differ significantly between TMS responders and non-responders. Secondary objectives include identifying predictive biomarkers for TMS efficacy and assessing biological changes correlated with clinical improvement.
Primary outcomes will focus on identifying molecular signatures that correlate with treatment responsiveness. Secondary outcomes will include changes in depression severity scores, documentation of any adverse effects related to TMS, and examination of correlations between biomarker expression and pharmacological history.
This study is crucial for advancing personalized treatment approaches in psychiatry. By identifying objective, blood-based biomarkers of TMS response, it may become possible to tailor treatment strategies, reduce unnecessary interventions, and improve therapeutic outcomes for individuals suffering from TRD.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective, single-group, open-label cohort study designed to evaluate the association between plasma proteomic and metabolomic profiles and clinical response to transcranial magnetic stimulation (TMS) in patients with treatment-resistant depression (TRD). All participants in the intervention arm will receive a standardized TMS protocol targeting the left dorsolateral prefrontal cortex. A group of age- and sex-matched healthy individuals will serve as a non-randomized control group for baseline biomarker comparison. No randomization or blinding will be employed.
| Arm | Type | Receives |
|---|---|---|
| Transcranial Magnetic Stimualtion Treatment Arm | Experimental | Device: TMSThis arm includes participants diagnosed with treatment-resistant depression (TRD) who will receive transcranial magnetic stimulation (TMS) therapy. TMS will be delivered using the MagVenture™ X100™ device. The treatment protocol consists of 20 sessions over a 4-week period (5 sessions per week). Stimulation will target the left dorsolateral prefrontal cortex (DLPFC) using intermittent theta burst stimulation (iTBS). Motor threshold will be determined at baseline and reassessed weekly to calibrate stimulation intensity at 90% of the resting motor threshold. Blood samples will be collected from participants at two time points: prior to the first TMS session (pre-treatment) and following the final (20th) session (post-treatment). Proteomic and metabolomic analyses will be performed using high-resolution liquid chromatography-mass spectrometry (LC-MS). The goal is to identify differentially expressed proteins and metabolites associated with clinical response to TMS. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Diagnosis of Major Depressive Disorder (MDD) according to DSM-5-TR criteria.
- Inadequate clinical response to at least two different antidepressants and/or anti-obsessive agents administered at therapeutic doses and durations.
- Clinical symptoms not better explained by metabolic or organic medical conditions.
- No epileptic activity detected on routine electroencephalography (EEG) prior to TMS initiation.
- Routine pre-TMS laboratory tests reveal no abnormalities that may significantly affect treatment response, including:
Key exclusion criteria (13 listed)
- Any contraindication to TMS as identified in the standardized pre-TMS risk assessment form.
- Presence of epileptic focus detected on pre-TMS EEG.
- History of significant head trauma, loss of consciousness, or intracranial surgery.
- Presence of metal implants or foreign bodies incompatible with TMS (e.g., aneurysm clips, surgical clamps, metallic fragments).
- Abnormal thyroid hormone levels in pre-TMS laboratory testing.
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 |
|---|---|---|
| TMSTranscranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique approved for the treatment of major depressive disorder (MDD), particularly in individuals with treatment-resistant depression (TRD). TMS targets the left dorsolateral prefrontal cortex (DLPFC), a brain region often underactive in depression, and modulates neural activity through magnetic pulses. This study aims to evaluate the effects of TMS on plasma proteomic and metabolomic profiles in patients with TRD. Participants will undergo 20 sessions of intermittent theta burst stimulation (iTBS) over four weeks. Blood samples will be collected before and after treatment to identify molecular changes associated with clinical response. Healthy controls will provide single-time-point blood samples for baseline comparison. Findings may support the development of biomarker-based strategies for personalized treatment in psychiatry. | Device | Transcranial Magnetic Stimualtion Treatment Arm |
Primary outcome
Plasma Proteomic Profile Changes After TMS in Patients with Treatment-Resistant Depression
Time frame: From enrollment to end of treatment at 4 weeks
Assessment of differences in plasma proteomic profiles in treatment-resistant depression (TRD) patients before and after transcranial magnetic stimulation (TMS), using high-resolution liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Changes in protein expression will be used to identify potential biomarkers of treatment response.
Plasma Metabolomic Profile Changes After TMS in Patients with Treatment-Resistant Depression
Time frame: From enrollment to end of treatment at 4 weeks
Evaluation of global metabolomic changes in plasma of TRD patients pre- and post-TMS therapy. Analysis will be conducted via liquid chromatography-mass spectrometry with ion mobility separation (LC-TIMS-TOF-MS), enabling identification of differential metabolites associated with clinical outcomes.
Fold Change in Baseline Proteomic Markers Between Treatment Responders and Non-Responders
Time frame: From enrollment to end of the treatment at 4 weeks
Differences in baseline proteomic markers between treatment responders and non-responders will be assessed using LC-MS/MS. Fold change values will be calculated to identify proteins with significant differential expression between the two groups.
Variable Importance in Projection Scores of Predictive Proteins
Time frame: Baseline and End of 4-week treatment
Variable Importance in Projection scores will be calculated using multivariate statistical analysis (e.g., PLS-DA) to rank the importance of baseline proteomic markers in distinguishing treatment responders from non-responders.
Area Under the ROC Curve for Predictive Proteomic Markers Between Treatment Responders and Non-Responders
Time frame: Baseline and End of 4-week treatment
Receiver Operating Characteristic (ROC) curve analysis will be performed to evaluate the predictive performance of baseline and end-of-treatment proteomic markers in distinguishing treatment responders from non-responders. Area Under the Curve (AUC) values will be calculated to assess discriminative ability.
Fold Change in Baseline Plasma Metabolomic Markers Between TMS Responders and Non-Responders
Time frame: Baseline
Fold change in baseline plasma metabolomic expression levels will be assessed between TMS treatment responders and non-responders using LC-MS/MS. The analysis aims to identify significantly altered metabolites that may predict treatment response.
Variable Importance in Projection Scores of Baseline Plasma Metabolomic Markers Between TMS Responders and Non-Responders
Time frame: Baseline and End of 4-week treatment
Variable Importance in Projection scores will be calculated using multivariate statistical models (e.g., PLS-DA) to rank baseline plasma metabolomic markers according to their importance in differentiating TMS treatment responders from non-responders. Unitless
Area Under the ROC Curve of Baseline Plasma Metabolomic Markers Between TMS Responders and Non-Responders
Time frame: Baseline and End of 4-week treatment
Receiver Operating Characteristic curve analysis will be conducted to evaluate the predictive accuracy of baseline plasma metabolomic markers in distinguishing TMS treatment responders from non-responders. The Area Under Curve (AUC)will quantify each marker's discriminative ability. Measurement Tool: ROC curve analysis Unit of Measure: AUC (0-1 scale)
6 secondary outcomes
Change in Depression Severity Based on Hamilton Depression Rating Scale (HAM-D, 17-item)
Time frame: From enrollment to the end of the treatment at 4 weeks
Change in Depression Severity Based on Patient Health Questionnaire-9 (PHQ-9)
Time frame: From enrollment to the end of the treatment at 4 weeks
Change in Subjective Sleep Quality Measured by Pittsburgh Sleep Quality Index [Sleep Quality]
Time frame: From enrollment to end of the treatment 4 weeks
Correlation Between Antidepressant Medication Use and Clinical Response to TMS Measured by Hamilton Depression Rating Scale-17
Time frame: From enrollment to end of the treatment at 4 weeks
Change in Headache and Scalp Pain Severity Measured by Visual Analog Scale (VAS) [Tolerability]
Time frame: Baseline and End of 4-week treatment
Incidence of Seizure Events
Time frame: From enrollment to end of the 4 weeks
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 11 Sep 2026.
- Individual participant dataSharing planned: Yes. Individual Participant Data (IDP) will be shared together with the Clinical Study Report
Related trials for Major Depression Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
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 TMS in people with Major Depression Disorder, 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 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 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, Medical Doctor (+903123044512, beyazitgarip@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Proteomic Profile Changes After TMS in Patients with Treatment-Resistant Depression (time frame: From enrollment to end of treatment at 4 weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.