Phase-Locked Accelerated Intermittent Theta Burst Stimulation for Treatment-Resistant Depression
Development of Precision Medicine in the Field of iTBS on Patients With TRD Using Multimodal Functional Brain Imaging and Deep Learning
This study aims to investigate whether synchronizing accelerated intermittent theta burst stimulation (aiTBS) with an individual's ongoing brain activity improves treatment outcomes in adults with Treatment-Resistant Depression (TRD).
Participants were randomly assigned to one of two treatment groups:
- Phase-locked aiTBS (PL-aiTBS): Magnetic stimulation was synchronized with a specific phase of ongoing brain activity measured using electroencephalography (EEG).
- Random-phase aiTBS (RP-aiTBS): Participants received the same stimulation protocol without synchronization to a specific phase of brain activity.
Both groups received personalized stimulation based on their individual theta frequency. Treatment consisted of 10 sessions over three consecutive days, with three sessions on Day 1, three sessions on Day 2, and four sessions on Day 3 (3-3-4 schedule). Each session delivered 1,800 magnetic pulses, resulting in a total of 18,000 pulses per participant.
The primary objective was to compare changes in depressive symptoms between the two treatment groups. Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline (before the first stimulation session), mid-treatment (after the sixth session, Day 2), post-treatment (after the tenth session, Day 3), and follow-up (Day7).
Resting-state EEG recordings were collected before and after stimulation sessions to investigate treatment-related changes in neural oscillatory activity, phase-amplitude coupling, functional connectivity, and other neurophysiological measures, as well as their potential associations with improvements in depressive symptoms.
Panoramica dello studio
Stato
Condizioni
Tipo di studio
Iscrizione (Effettivo)
Fase
- Non applicabile
Contatti e Sedi
Luoghi di studio
-
-
Taipei City
-
Taipei, Taipei City, Taiwan, 112
- Cheng Hsin General Hospital
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Adults aged 18 to 70 years.
- Diagnosis of major depressive disorder (MDD).
- Inadequate response to at least two antidepressant trials of adequate dose and duration.
- A 17-item Hamilton Depression Rating Scale (HAM-D) score of 9 or higher.
- A Montgomery-Åsberg Depression Rating Scale (MADRS) score of 16 or higher.
- Willingness to participate in the study and provision of written informed consent.
Exclusion Criteria:
- Other psychiatric disorders or serious medical conditions.
- Psychotic disorders.
- Current illicit drug use or alcohol use disorder.
- Neurological or seizure disorders.
- Contraindications to transcranial magnetic stimulation (TMS), including cardiac pacemakers or metallic implants.
- Pregnancy or postpartum depression.
- Electroconvulsive therapy (ECT) within the previous 12 months.
- Unstable medical illness.
- Inability to comply with study procedures.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Phase-Locked Accelerated iTBS (PL-aiTBS)
Participants received individualized accelerated intermittent theta burst stimulation (aiTBS) synchronized to a specific phase of ongoing frontal theta oscillations measured using EEG. |
Stimulation was delivered to the left dorsolateral prefrontal cortex (DLPFC; F3) using an individualized theta-frequency-based iTBS protocol. Each participant received 10 sessions over three consecutive days (3-3-4 schedule), with 1,800 pulses per session (18,000 pulses total). Stimulation was synchronized to the trough of ongoing frontal theta oscillations using real-time EEG phase estimation. |
|
Comparatore attivo: Random-Phase Accelerated iTBS (RP-aiTBS)
Participants received the same individualized aiTBS protocol without phase-locked synchronization to ongoing frontal theta oscillations. |
Participants received the same individualized iTBS protocol targeting the left DLPFC (F3), consisting of 10 sessions over three consecutive days (3-3-4 schedule), with 1,800 pulses per session (18,000 pulses total). Stimulation was delivered without phase-locked synchronization to ongoing frontal theta oscillations. |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Change in HAM-D Total Score
Lasso di tempo: Baseline (Day 1), Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAM-D), with total scores ranging from 0 to 52. Higher scores indicate greater depressive symptom severity. Changes in total scores from baseline were evaluated at each post-baseline assessment. |
Baseline (Day 1), Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
|
Change in MADRS Total Score
Lasso di tempo: Baseline (Day 1), Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), with total scores ranging from 0 to 60. Higher scores indicate greater depressive symptom severity. Changes in total scores from baseline were evaluated at each post-baseline assessment. |
Baseline (Day 1), Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Response Rate Based on HAM-D
Lasso di tempo: Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
Treatment response was defined as a reduction of at least 50% in HAM-D total score relative to baseline. The response rate was calculated as the percentage of participants meeting this criterion at each assessment time point. |
Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
|
Response Rate Based on MADRS
Lasso di tempo: Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
Treatment response was defined as a reduction of at least 50% in MADRS total score relative to baseline. The response rate was calculated as the percentage of participants meeting this criterion at each assessment time point. |
Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
|
Remission Rate Based on HAM-D17
Lasso di tempo: Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
Remission was defined as a HAM-D17 total score of 7 or lower. The remission rate was calculated as the percentage of participants meeting this criterion at each assessment time point. |
Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
|
Remission Rate Based on MADRS
Lasso di tempo: Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
Remission was defined as a MADRS total score of 10 or lower. The remission rate was calculated as the percentage of participants meeting this criterion at each assessment time point. |
Mid-treatment (Day 2), Post-treatment (Day 3), and Follow-up (Day 7)
|
Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Change From Baseline in Resting-State EEG Spectral Power
Lasso di tempo: Before and after each of the 10 stimulation sessions over the 3-day treatment period (Days 1-3).
|
Resting-state electroencephalography (EEG) was recorded to assess changes in neural oscillatory activity following accelerated intermittent theta burst stimulation (aiTBS). Spectral power was quantified across conventional frequency bands, including delta, theta, alpha, beta, and gamma. Changes in spectral power from baseline were evaluated across treatment stages. |
Before and after each of the 10 stimulation sessions over the 3-day treatment period (Days 1-3).
|
|
Change From Baseline in Resting-State EEG Phase-Amplitude Coupling
Lasso di tempo: Before and after each of the 10 stimulation sessions over the 3-day treatment period (Days 1-3).
|
Resting-state EEG was analyzed to assess phase-amplitude coupling (PAC), reflecting the relationship between the phase of lower-frequency oscillations and the amplitude of higher-frequency activity. Changes in PAC strength from baseline were evaluated across treatment stages to characterize neurophysiological effects of aiTBS. |
Before and after each of the 10 stimulation sessions over the 3-day treatment period (Days 1-3).
|
|
Resting-State EEG Functional Connectivity
Lasso di tempo: Before and after each of the 10 stimulation sessions over the 3-day treatment period (Days 1-3).
|
Resting-state EEG functional connectivity was assessed using phase-based synchronization measures between brain regions. Changes in functional connectivity from baseline were evaluated across treatment stages to investigate stimulation-related alterations in neural synchronization. |
Before and after each of the 10 stimulation sessions over the 3-day treatment period (Days 1-3).
|
|
Change From Baseline in Resting-State EEG Microstate Parameters
Lasso di tempo: Before and after each of the 10 stimulation sessions over the 3-day treatment period (Days 1-3).
|
Resting-state EEG microstate analysis was used to characterize changes in the temporal dynamics of large-scale brain network activity. Microstate parameters included mean duration (ms), occurrence rate (events/s), time coverage (%), and transition probabilities between microstate classes. Changes in these parameters were evaluated across treatment sessions to investigate stimulation-related alterations in brain network dynamics. |
Before and after each of the 10 stimulation sessions over the 3-day treatment period (Days 1-3).
|
Collaboratori e investigatori
Sponsor
Collaboratori
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- (985)111A-63
- (1126)113A-56 (Altro identificatore: Cheng Hsin General Hospital Institutional Review Board)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
Individual participant data will not be shared publicly due to participant confidentiality and privacy considerations. No external IPD sharing is currently planned.
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .