Amygdala-Targeted Transcranial Temporal Interference Stimulation for Major Depressive Disorder: A Randomized Sham-Controlled Trial of Clinical Efficacy and Neurobiological Mechanisms
Amygdala-targeted Temporal Interference Stimulation for Major Depressive Disorder。
This randomized, sham-controlled clinical trial aims to evaluate the efficacy and safety of amygdala-targeted transcranial temporal interference stimulation (tTIS) in adults with major depressive disorder (MDD) and to explore its potential neurobiological mechanisms.
The main questions this study aims to answer are:
Whether active amygdala-targeted tTIS reduces depressive symptoms compared with sham stimulation.
Whether tTIS produces changes in amygdala-related neural activity and functional brain networks that are associated with clinical improvement.
Participants will be randomly assigned to receive either active tTIS or sham stimulation. They will complete a course of stimulation sessions and undergo clinical assessments before and after the intervention. Neuroimaging assessments will also be performed to investigate treatment-related changes in the amygdala and associated brain networks.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: Jingjing Huang
- Telefonnummer: 021-68306699*1222
- E-mail: huangjingjing18@tongji.edu.cn
Studiesteder
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Kina, 201204
- Shanghai Pudong New Area Mental Health Center
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Kontakt:
- Jingjing Huang
- Telefonnummer: 021-68306699*1222
- E-mail: huangjingjing18@tongji.edu.cn
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-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Aged 18 to 55 years, inclusive, with no restriction on sex.
- Diagnosed with Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), as determined by a study physician.
- A 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥17 at screening/baseline.
- The antidepressant medication regimen must remain stable from at least 30 days before signing the informed consent form through the study period.
- In the judgment of the investigator, the participant or their legally authorized representative is able to understand the purpose and procedures of the study, comply with the study protocol, and provide written informed consent.
Exclusion Criteria:
- A history of other psychiatric disorders, neurological disorders, or substance abuse that, in the investigator's judgment, may interfere with the assessment of treatment efficacy.
- A history of epilepsy, seizures, or convulsive episodes.
- Presence of intracranial metallic foreign bodies or metallic implants in or near the heart.
- Presence of organic brain disease, or a history of severe head injury or cranial surgery.
- Receipt of electroconvulsive therapy (ECT) or other physical treatments, such as transcranial magnetic stimulation (TMS), within the 30 days before enrollment.
- An unstable psychiatric condition or significant suicide risk, as assessed by the investigator.
- Women who are pregnant or breastfeeding.
- Current participation in another interventional clinical trial.
- Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in this study.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Tredobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
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Eksperimentel: Active tTIS
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Active transcranial temporal interference stimulation (tTIS) will be delivered using two pairs of scalp electrodes. Two high-frequency alternating currents with slightly different carrier frequencies will be applied to generate a low-frequency temporal interference envelope within the targeted amygdala region. Electrode placement and stimulation parameters will be determined according to the study protocol and individualized electric-field modeling when applicable. Participants assigned to the active group will receive 10 stimulation sessions, with each session lasting 30 minutes, according to the predefined treatment schedule. |
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Sham-komparator: Sham tTIS
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Participants assigned to the sham group will undergo the same electrode placement and treatment procedures as the active stimulation group. Sham stimulation will include brief ramp-up and ramp-down periods to mimic the initial sensory experience of active stimulation, without delivering continuous therapeutic stimulation during the remainder of the session. |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score
Tidsramme: Baseline; after 10 stimulation sessions (30 minutes per session; end of Week 2)
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The 17-item Hamilton Depression Rating Scale (HAMD-17) is a clinician-rated scale used to assess the severity of depressive symptoms. Total scores range from 0 to 52, with higher scores indicating greater depressive symptom severity. The primary outcome is the change in HAMD-17 total score from baseline to the end of the 10-session intervention. |
Baseline; after 10 stimulation sessions (30 minutes per session; end of Week 2)
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Tidsramme: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
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The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated scale used to assess the severity of depressive symptoms. Total scores range from 0 to 60, with higher scores indicating greater depressive symptom severity. Changes in MADRS total score from baseline will be assessed following treatment and during follow-up. |
Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
|
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Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score Across Treatment and Follow-up
Tidsramme: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
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Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
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Change in Hamilton Anxiety Rating Scale (HAMA) Total Score
Tidsramme: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
|
The Hamilton Anxiety Rating Scale (HAMA) is a clinician-rated scale used to assess the severity of anxiety symptoms. Total scores range from 0 to 56, with higher scores indicating greater anxiety severity. Changes in HAMA total score from baseline will be assessed following treatment and during follow-up. |
Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
|
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Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score
Tidsramme: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
|
The Snaith-Hamilton Pleasure Scale (SHAPS) is used to assess anhedonia and reduced capacity to experience pleasure. Changes in SHAPS score from baseline will be used to evaluate treatment-related changes in hedonic functioning. |
Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
|
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Change in Pittsburgh Sleep Quality Index (PSQI) Global Score
Tidsramme: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
|
The Pittsburgh Sleep Quality Index (PSQI) is a self-reported measure of sleep quality and sleep disturbances. The global score ranges from 0 to 21, with higher scores indicating poorer sleep quality. Changes in PSQI global score from baseline will be assessed following treatment and during follow-up. |
Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
|
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Change in World Health Organization Quality of Life-BREF (WHOQOL-BREF) Domain Scores
Tidsramme: Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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The WHOQOL-BREF is a self-reported measure of quality of life across physical health, psychological health, social relationships, and environmental domains. Higher domain scores indicate better perceived quality of life. Changes in domain scores from baseline will be assessed after treatment and during follow-up. |
Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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Change in Generalized Anxiety Disorder-7 (GAD-7) Score
Tidsramme: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
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The Generalized Anxiety Disorder-7 (GAD-7) is a self-reported measure of anxiety symptoms. Total scores range from 0 to 21, with higher scores indicating greater anxiety symptom severity. Changes in GAD-7 score from baseline will be assessed following treatment and during follow-up. |
Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
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Change in Patient Health Questionnaire-9 (PHQ-9) Total Score
Tidsramme: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
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The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-reported measure used to assess the severity of depressive symptoms. Total scores range from 0 to 27, with higher scores indicating greater depressive symptom severity. Changes in PHQ-9 total score from baseline will be assessed following treatment and during follow-up. |
Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.
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Change in Cognitive Performance Assessed by the THINC-integrated Tool (THINC-it)
Tidsramme: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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The THINC-integrated Tool (THINC-it) is a computerized cognitive assessment designed to evaluate subjective and objective cognitive functioning, including attention, processing speed, working memory, and executive function. Changes in THINC-it performance from baseline will be assessed following treatment and during follow-up. |
Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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Change in Temporal Experience of Pleasure Scale (TEPS) Score
Tidsramme: Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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The Temporal Experience of Pleasure Scale (TEPS) is a self-reported measure of anticipatory and consummatory pleasure. Changes in TEPS scores from baseline will be explored to assess treatment-related changes in reward-related emotional experience. |
Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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Change in Emotion Regulation Questionnaire (ERQ) Score
Tidsramme: Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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The Emotion Regulation Questionnaire (ERQ) assesses habitual use of cognitive reappraisal and expressive suppression as emotion regulation strategies. Changes in ERQ scores from baseline will be explored following treatment and during follow-up. |
Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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Andre resultatmål
Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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DTI
Tidsramme: Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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Diffusion tensor imaging (DTI) will be used to explore treatment-related changes in white matter microstructural measures within neural pathways associated with the amygdala and emotion-regulation networks. |
Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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fMRI
Tidsramme: Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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Functional magnetic resonance imaging (fMRI) will be used to assess treatment-related changes in functional connectivity involving the amygdala and brain regions associated with emotional processing and regulation. Amygdala-based functional connectivity measures will be compared across study time points. |
Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.
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Incidence of Treatment-Emergent Adverse Events
Tidsramme: From the first stimulation session through the 4-week follow-up
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From the first stimulation session through the 4-week follow-up
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
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Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
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