Transcranial Magnetic Stimulation in Patients With a Depressive Episode - RCT Trial

Study Overview
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Brief Summary
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The study is planned as a randomized, double-blind, active comparator-controlled and sham-controlled parallel trial, in which raters and participants will be blinded to the group selection. A total of 60 participants, meeting the eligibility criteria, will be enrolled in the study and divided randomly into 4 groups (2 experimental ones with active rTMS or iTBS and 2 controls with sham-placebo rTMS or iTBS stimaltions).

Detailed Description
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The study is planned as a randomized, double-blind, active comparator-controlled and sham-controlled parallel trial, in which raters and participants will be blinded to the group selection. A total of 60 participants, meeting the eligibility criteria, will be enrolled in the study and divided randomly into 4 groups (2 experimental ones and 2 controls): EG1 (N=20) rTMS stimulation (1 session daily per 30 days, 3000 pulses per session, session time = 37,5 minutes, 10Hz), EG2 (N=20) iTBS stimulation (4 short sessions daily per 14 days, 600 pulses per session, session time=3 minutes, 50Hz), CG1 (N=10) placebo (sham-coil) stimulation based on rTMS protocol, CG2 (N=10) placebo (sham-coil) stimulation based on iTBS protocol. Efficacy will be analyzed on the intention-to-treat population, defined as participants who completed the baseline and at least one evaluation after rTMS intervention. The following are the inclusion and exclusion criteria for the recruitment process: The following stimulation protocols will be used to conduct research into the treatment of depressive disorders: Stimulation with rTMS within the left hemisphere, in the dorsolateral prefrontal cortex, DLPFC (Dorsolateral prefrontal cortex). In the field of stimulation, a protocol based on FDA recommendations, so- called train stimulation (stimulation of a given frequency for a short period of time with longer breaks without stimulation) assuming the following stimulation parameters: Magnetic field intensity: 120% of the initial excitability threshold for the motor cortex, Frequency: 10 Hz for 4 seconds of stimulation, Breaks in stimulation: 26 seconds, Total number of stimulation pulses: 3000, Duration of one session: 37.5 minutes, Duration of therapy: from 4 to 6 weeks (sessions on days 1-5, break on days 6 and 7). iTBS protocol in the left cerebral hemisphere, in the dorsolateral prefrontal cortex, DLPFC (Dorsolateral prefrontal cortex). Expected range of parameters: Frequency: up to 50 Hz, Intensity: 80% excitability threshold for the motor cortex, Breaks between pulse series: up to 10 seconds Duration of a single session: from 20 to 190 seconds, Duration of treatment: 40 sessions, Total number of pulses in a session: 600, sessions a day: 4. Duration of one session: 3 minutes, Duration of therapy: 2 weeks (sessions on days 1-5, break on days 6 and 7).

Official Title
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Transcranial Magnetic Stimulation in Patients With a Depressive Episode

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: TMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Psychiatric diagnosis (F3X); Symptom severity - total score of the Hamilton Depression Scale a least 17 Granting informed consent The possibility for the patient to ensure constant participation in individual sessions and clinical evaluations, in particular in terms of place of residence and travel options 18-70 years of age. Exclusion Criteria: Contraindications to treatments using TMS Lack of informed consent from the patient Documented persistent lack of cooperation in treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rTMS active<br> | Device: TMS<br>* rTMS (30sessions) or iTBS (40sessions)<br>|
| Sham Comparator: rTMS sham<br> | Device: TMS<br>* rTMS (30sessions) or iTBS (40sessions)<br>|
| Experimental: iTBS active<br> | Device: TMS<br>* rTMS (30sessions) or iTBS (40sessions)<br>|
| Sham Comparator: iTBS sham<br> | Device: TMS<br>* rTMS (30sessions) or iTBS (40sessions)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of efficiency of rTMS and iTBS active stimulation Change from Baseline to END of stimulation regarded as reduction of symptoms measured in MADRS scale | Comparison of efficiency of rTMS and iTBS active stimulation from baseline to end of stimualion measured with MADRS. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. | END of stimulation | 
| Comparison of efficiency of rTMS and iTBS active stimulation Change from Baseline to 3 months of follow up after end of stimulation regarded as reduction of symptoms measured in MADRS scale | Comparison of efficiency of rTMS and iTBS active stimulation from baseline to 3 months follow up after end of stimualion measured with MADRS. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. | 3 months after end of stimulation | 
| Comparison of efficiency of rTMS and iTBS active stimulation Change from Baseline to END of stimulation regarded as reduction of symptoms measured in HAMD scale | Comparison of efficiency of rTMS and iTBS active stimulation from baseline to end of stimualion measured with HAMD. The HAMD is a 17-items scale, measuring depression severity, the overall score ranges from 0 to 60, higher score means more severe depression. | END of stimulation | 
| Comparison of efficiency of rTMS and iTBS active stimulation Change from Baseline to 3 months of follow up after end of stimulation regarded as reduction of symptoms measured in HAMD scale | Comparison of efficiency of rTMS and iTBS active stimulation from baseline to 3 months follow up after end of stimualion measured with HAMD. The HAMD is a 17-items scale, measuring depression severity, the overall score ranges from 0 to 60, higher score means more severe depression. | 3 months after end of stimulation | 
| Comparison of efficiency of rTMS active and rTMS sham-placebo stimulation Change from Baseline to END of stimulation regarded as reduction of symptoms measured in MADRS scale | Comparison of efficiency of rTMS active and rTMS sham placebo stimulation from baseline to end of stimulation measured with MADRS. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. | END of stimulation | 
| Comparison of efficiency of rTMS active and rTMS sham placebo stimulation from baseline to end of stimulation measured with MADRS | Comparison of efficiency of iTBS active and iTBS sham-placebo stimulation Change from Baseline to END of stimulation regarded as reduction of symptoms measured in MADRS scale. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. | 3 months after end of stimulation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMS, iTBS, MDD, RCT