Blood markers that predict TMS response in treatment-resistant depression
The Relationship Between Plasma Metabolomics and Proteomics Profiling and Response to Transcranial Magnetic Stimulation Therapy in Treatment-Resistant Depression
This project will test whether blood protein and metabolic markers can predict how well transcranial magnetic stimulation (TMS) works for people with treatment-resistant depression.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 55 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Gulhane Training and Research Hospital Government |
| Locations | 2 sites (Ankara, Ankara and 1 other locations) |
| Trial ID | NCT07039370 on ClinicalTrials.gov |
What this trial studies
This is a prospective cohort study enrolling 55 adults with treatment-resistant major depressive disorder and 55 age- and sex-matched healthy controls. Patients will receive a standardized TMS protocol of 20 intermittent theta burst stimulation (iTBS) sessions over four weeks targeting the left dorsolateral prefrontal cortex, with motor threshold calibrated weekly. Plasma samples will be collected before the first TMS session and after the 20th session for proteomic and metabolomic profiling, and profiles will be compared to clinical treatment response. The goal is to identify blood-based molecular signatures that predict or reflect clinical benefit from TMS.
Who should consider this trial
Good fit: Adults (18+) with major depressive disorder who have not adequately responded to at least two antidepressant trials and who pass standard pre-TMS medical and EEG screening are ideal candidates.
Not a fit: People whose depression is not classified as treatment-resistant, who have contraindications to TMS (for example, epileptic activity or incompatible implants), or who cannot attend in-person sessions are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, this could let clinicians use a blood test to predict who is likely to benefit from TMS, shortening time to effective treatment and avoiding ineffective interventions.
How similar studies have performed: Previous work has found some neuroimaging and peripheral biomarkers associated with TMS response, but blood-based proteomic and metabolomic predictors are still exploratory with mixed results to date.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 * 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. Exclusion Criteria: * 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. * 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.
Where this trial is running
Ankara, Ankara and 1 other locations
- Gulhane Training and Research Hospital — Ankara, Ankara, Turkey (Türkiye) (Recruiting)
- Gulhane Training and Research Hospital — Ankara, Ankara, Turkey (Türkiye) (Recruiting)
Study contacts
- Study coordinator: BEYAZIT GARİP, Medical Doctor
- Email: beyazitgarip@gmail.com
- Phone: +903123044512
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.