Theta Burst Stimulation With an 8-Coil Versus H1-Coil for Resistant Depression (rTBShTBS)

Randomized Controlled Trial of Two Accelerated Transcranial Magnetic Stimulation Methods in the Treatment of Resistant Depression: Intermittent Theta Burst Stimulation With an 8-Coil Versus H1-Coil

The goal of this clinical trial is to compare response rates after treatment with Figure Eight-Coil TMS versus H-Coil TMS on the prefrontal cortex left dorsolateral, in patients suffering from depression resistant. The main question it aims to answer is:

rTBS (accelerated neuronavigated intermittent Theta Burst Stimulation) is more effective than hTBS (accelerated deep intermittent Theta Burst Stimulation) in the treatment of resistant depression in terms of response rate.?

Researchers will compare Figure Eight-Coil TMS (rTBS) versus H-Coil TMS (hTBS) to see if rTBS is more effective than hTBS.

Participants will:

• Receive, for each stimulation method, 8 sessions per day spaced 50 minutes apart, over 5 days.
• Have visit all day of stimulation for checkups and tests.
• Have a a research MRI before and after treatment.
• Have follow-up visits at 1 month, 2 months, 3 months, 6 months, and 12 months post-treatment, via teleconsultation.

Study Overview

• Status: Not yet recruiting
• Conditions: Treatment of Resistant Depression; H1-Coil; Theta Burst Stimulation
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dominique Professor Januel, Professor of Medicine; Phone Number: +33143093232 0143093232; Email: d.januel@epsve.fr
• Study Contact Backup: Name: Youcef Bencherif, Project Manager; Phone Number: +33143093232 0143093232; Email: y.bencherif@epsve.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over 18 years of age
• Presenting a major depressive episode according to the DSM-5-TR criteria, occurring as part of major depressive disorder (unipolar depression)
• The major depressive episode must meet the criteria for treatment resistance, defined by a lack of response to at least two different antidepressant treatments prescribed at an effective dose for a duration of 6 weeks or more
• Stable treatment for at least 6 weeks
• Affiliation with a social security system or State Medical Assistance (Aide Médicale d'État)
• Patient agrees to participate in the study and has signed an informed consent form

Exclusion Criteria:

• Presence of a contraindication to TMS: epilepsy, intracranial foreign body, cochlear implant, retinal implant, pacemaker
• Presence of a bipolar disorder according to DSM-5-TR criteria
• Presence of catatonic or psychotic features during the current episode
• Presence of severe psychiatric disorders other than a major depressive episode
• Presence of neurological disorders
• Unstable epilepsy
• Current moderate to severe addiction disorders other than caffeine and/or tobacco
• Current suicidal ideation
• Use of any brain stimulation treatment (ECT, rTMS, tDCS) for the current episode
• Pregnancy or breastfeeding
• Women of childbearing potential without effective contraception
• Persons under guardianship or legal protection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: rTMS ARM; The treatment consists of 8 sessions per day for 5 days, with daily self-assessments for 1 week. Each session lasts approximately 9 minutes and 50 seconds with a 50-minute break between sessions. The application of rTBS will be done using the Cool-B65 coil, targeting the DLPFC region identified by neuronavigation.	Device: repetitive transcranial magnetic stimulation; A burst of 3 pulses sent at a frequency of 50 Hz, repeated with a frequency of 5 Hz for 2 seconds, followed by an 8-second pause. This sequence is repeated for 59 cycles, totaling 9 minutes and 50 seconds, with a total of 1800 pulses.
Other: hTBS Arm; The treatment consists of 8 sessions per day for 5 days, with daily self-assessments for 1 week. Each session lasts approximately 9 minutes and 50 seconds with a 50-minute break between sessions. The application of hTBS will be done using the H1 coil, targeting the DLPFC region located 6 cm forward from the motor cortex.	Device: repetitive transcranial magnetic stimulation; A burst of 3 pulses sent at a frequency of 50 Hz, repeated with a frequency of 5 Hz for 2 seconds, followed by an 8-second pause. This sequence is repeated for 59 cycles, totaling 9 minutes and 50 seconds, with a total of 1800 pulses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The response rate according to the MADRS scale	The response rate is defined as an improvement of more than 50% compared to baseline on the MADRS clinical scale (Montgomery-Asberg Depression Rating Scale). The MADRS consists of 10 items, each scored from 0 to 6 : depressive mood, appetite, sleep, psychomotor retardation, anxiety, suicidal thoughts, cognitive impairment, pessimism, loss of control and demoralization. The total score is the sum of the scores for all 10 items. The overall score can range from 0 to 60. 0 to 6: No depression 7 to 19: Mild depression 20 to 34: Moderate depression 35 to 60: Severe depression	Before the treatment and after the treatment at 5 day.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement of treatment-resistant depression	We use: - MADRS (Montgomery-Åsberg Depression Rating Scale) : Remission: A MADRS score of less than 10.	Before the treatment and after the treatment at 5 days.
Clinical improvement of treatment-resistant depression	We use: - HDRS-17 (Hamilton Depression Rating Scale - 17 items): The scale contains 17 items, each scored on a scale from 0 to 4, 0 to 2, or 0 to 3, depending on the item. The total score is obtained by adding the scores of all 17 items. The total score can range from 0 to 52. Response: A reduction of 50% or more in the total HDRS-17 score compared to baseline is generally considered a response to treatment. Remission: A score of 7 or less is typically considered remission from depression.	Before the treatment and after the treatment at 5 days.
Clinical improvement of treatment-resistant depression	We use: - QIDS-SR : The patient answers the 16 items, each assessing various depressive symptoms, and the score ranges from 0 to 27, based on their experiences over the past week. A 50% reduction in the total score from baseline is considered a response.	Before the treatment and after the treatment at 5 days.
Clinical improvement of treatment-resistant depression	We use: - EQ5D : The EQ-5D is a brief tool for assessing health-related quality of life. It measures 5 key dimensions of health.	Before the treatment and after the treatment at 5 days.
Tolerance to treatment	Rate of adverse effects and rate of premature withdrawal from the study.	Each visits of clinical trial : each day of treatment (5 days), at 1 month, 2 month, 3 month, 6 month and 12 month.
Improvement of cognitive functions.	Trail Making Test A and B (version from the Group for the Evaluation of Executive Functions, GREFEX, Army individual test 1944, based on Godefroy, 2012)	Before the treatment and after the treatment at 5 day.
Improvement of cognitive functions.	Free Recall / Cued Recall at 16 items (RL/RI-16), version A or B	Before the treatment and after the treatment at 5 day.
Improvement of cognitive functions.	Stroop Test (Golden, 1978)	Before the treatment and after the treatment at 5 day.
Improvement of cognitive functions.	Wisconsin Card Sorting Test (WCST), GREFEX version	Before the treatment and after the treatment at 5 day.
Improvement of cognitive functions.	N-back Task (version from the Attention Assessment Tests, TAP)	Before the treatment and after the treatment at 5 day.
Improvement of cognitive functions.	Go/No-Go Inhibition Task (TAP version)	Before the treatment and after the treatment at 5 day.
Improvement of cognitive functions.	Digit Span and "Coding" subtest from the Wechsler Adult Intelligence Scale (WAIS-IV)	Before the treatment and after the treatment at 5 day.
Improvement of cognitive functions.	Verbal Fluency Test (GREFEX version)	Before the treatment and after the treatment at 5 day.
Improvement of neurophysiological functions	Variation in brain functional connectivity between baseline and the end of the rTMS treatment.	Before the treatment and after the treatment at 5 day.
Improvement of neurophysiological functions	Neurobiological/neurophysiological variables: change in heart rate variability.	Before the treatment and after the treatment at 5 day.
Improvement of neurophysiological functions	Change in serum BDNF levels.	Before the treatment and after the treatment at 5 day.
Improvement of neurophysiological functions	Change in motor cortex neuroexcitability.	Before the treatment and after the treatment at 5 day.
Pain detection and pain tolerance using an experimental pain task	Cold pain using the cold pressor task and mechanical pain using the algomete	Before the treatment and after the treatment at 5 day.

Collaborators and Investigators

• Sponsor: Dominique JANUEL

Study record dates

Study Major Dates

• Study Start (Estimated): February 16, 2025
• Primary Completion (Estimated): November 18, 2027
• Study Completion (Estimated): November 18, 2028

Study Registration Dates

• First Submitted: January 27, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: TMS; Resistant Depression; Theta burst stimulation; H1-Coil; Accelerated Transcranial Magnetic Stimulation; Intermittent Theta Burst Stimulation with an 8-Coil versus H1-Coil
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 2024-A00954-43

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No