Personalized rTMS for Resistant Depression

Validation of Personalized Antidepressant Treatment by Neuromodulation - Pilot Study

The investigators hypothesize that personalizing the rTMS targets using functional MRI will increase its efficacy. The most dysfunctional regions or the most dysfunctional network will be stimulated homogeneously. Individualized rTMS will be compared to traditional rTMS procedure and to trans-cranial direct current stimulation (tDCS) in a randomized cross-over trial.

In this pilot study the primary outcome measure will be the correction of the MRI anomalies. Symptoms reduction and the proportion of remitters will be secondary outcome measurements.

Study Overview

• Status: Terminated
• Conditions: Depressive Disorder; Treatment-Resistant
• Intervention / Treatment: Procedure: Functional magnetic resonance imaging used to individualize rTMS protocol; Device: Individualized rTMS (transcranial magnetic stimulation); Device: Classical rTMS (transcranial magnetic stimulation); Device: Classical tDCS (transcranial direct current stimulation)

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67091
    • Service de Psychiatrie 1, Hôpital Civil, Hôpitaux Universitaires de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged from 18 to 65 Y
• Affiliated to the health insurance
• Having signed an informed consent
• Suffering from major depression according to the DSM5
• Unresponsive or incomplete remission after at least one trial of antidepressant (> 6 weeks at efficient dose or side effects)
• Treatment stable for > 6 weeks

Exclusion Criteria:

• Contraindication for MRI, rTMS or tDCS: non-removable ferromagnetic body, prosthesis, pacemaker, medication delivered by an implanted pump clip or vascular stent, heart valve or ventricular shunt, seizure disorders, skin pathology in the region of tDCS electrode placement.
• Pregnancy
• Severe and non-stabilized somatic pathology
• Patients deprived of liberty or hospitalized without their consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individualized rTMS (transcranial magnetic stimulation); The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 38). rCBF will be measured using the QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. The therapeutic protocol will be design to correct the rCBF anomaly first by defining each point where to deliver the stimulation than the stimulation protocol for each point (180% of active motor threshold, 4-second 10 Hz train duration, with 26-second intertrain interval for a total of 3000 pulses). The whole target will be homogeneously stimulated. The active motor threshold will be assessed. The procedure will be repeated twice a day for 10 days over 2 weeks.	Procedure: Functional magnetic resonance imaging used to individualize rTMS protocol; Procedure consisting in personalizing the rTMS targets and stimulation pattern based on functional magnetic resonance imaging; Device: Individualized rTMS (transcranial magnetic stimulation)
Active Comparator: Classical rTMS (transcranial magnetic stimulation); rTMS will be performed as usual using a figure-eight coil: Defining the active motor threshold. For each session positioning the coil on F3, stimulating at 180% of active motor threshold (10 Hz, 4-second train duration, and 26-second intertrain interval) for 37.5 minutes (3000 pulses per session), twice a day for 10 days over 2 weeks.	Procedure: Functional magnetic resonance imaging used to individualize rTMS protocol; Procedure consisting in personalizing the rTMS targets and stimulation pattern based on functional magnetic resonance imaging; Device: Classical rTMS (transcranial magnetic stimulation)
Active Comparator: Classical tDCS (transcranial direct current stimulation); tDCS will be performed as usual: After controlling for skin healthiness, the anode and the cathode will be respectively placed over F3 and right shoulder. A commercial devices (MagStim), will deliver a constant current of 2 mA through 25 cm2 saline-soaked rubber sponges for 20 min per session. The procedure will be repeated twice a day for 10 days over 2 weeks.	Procedure: Functional magnetic resonance imaging used to individualize rTMS protocol; Procedure consisting in personalizing the rTMS targets and stimulation pattern based on functional magnetic resonance imaging; Device: Classical tDCS (transcranial direct current stimulation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of rCBF anomalies	The target region will be defined by comparing the rCBF scan of the patient to a control population. rCBF will be measured using the average of 2 ∙ 3 (=6) measures of rCBF using QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. rCBF change of the target region will be compared before & after therapeutic protocol between the different procedures (ANOVA). Functional connectivity map of the target region will be performed by extracting its average temporal course and looking at the region(s) which activity is correlated. Contrast map of each patient will be compared to the one of a control population submitted to the same analysis. Change in the number of above threshold voxels (F-test, p < 0.05 uncorrected, extension > 1 cm3) will be compared before & after therapeutic procedure (ANOVA). rCBF's change of the target region will be compared before & after therapeutic protocol between the different procedures (ANOVA).	Difference between before (assessed once between D-7 to -1) and after (assessed once between D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Change of the functional connectivity anomalies	The target region will be defined by comparing the rCBF scan of the patient to a control population. rCBF will be measured using the average of 2 ∙ 3 (=6) measures of rCBF using QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. rCBF change of the target region will be compared before & after therapeutic protocol between the different procedures (ANOVA). Functional connectivity map of the target region will be performed by extracting its average temporal course and looking at the region(s) which activity is correlated. Contrast map of each patient will be compared to the one of a control population submitted to the same analysis. Change in the number of above threshold voxels (F-test, p < 0.05 uncorrected, extension > 1 cm3) will be compared before & after therapeutic procedure (ANOVA). rCBF's change of the target region will be compared before & after therapeutic protocol between the different procedures (ANOVA).	Difference between before (assessed once between D-7 to -1) and after (assessed once between D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in symptoms evaluated by the clinician (QIDS16-C)	See http://www.ids-qids.org/ for documentation relative to these scales. Computation will be performed in terms of : percentage of symptom reduction Number responders (reduction of more than 50% of symptoms) & numbers of remitters (QIDS16-C ≤ 6).	Difference between before (assessed once between D-7 to -1) and after (assessed once between D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol).
Change in symptoms evaluated by the patient (QIDS30-SR)	See http://www.ids-qids.org/ for documentation relative to these scales. Computation will be performed in terms of : percentage of symptom reduction Number responders (reduction of more than 50% of symptoms) & numbers of remitters (QIDS16-C ≤ 6).	Difference between before (assessed once between D-7 to -1) and after (assessed once between D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol).

Other Outcome Measures

Outcome Measure	Time Frame
Daily visual analogical scales assessing the core symptoms	Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol).
Response time and accuracy at the attentional network test	Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol).
Quality of life ("Echele synoptique des 3 temps")	Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol).
Global Assessment of Functioning	Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol).

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Investigators: Principal Investigator: Jack FOUCHER, MD, Hôpitaux Universitaires de Strasbourg

Publications and helpful links

General Publications

• Dormegny-Jeanjean LC, de Crespin de Billy C, Pierrat C, Mainberger O, Schorr B, Obrecht A, Arcay H, Moreau A, Humbert I, Scarlatti F, Bertschy G, de Sousa PL, Lamy J, Weibel S, Landre L, Foucher JR. Individualizing rTMS in treatment-resistant depression from patient-specific perfusion abnormalities a proof-of-concept randomized trial in comparison to standard rTMS and tDCS. Eur Arch Psychiatry Clin Neurosci. 2025 Jun 14. doi: 10.1007/s00406-025-02027-7. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2016
• Primary Completion (Actual): January 21, 2021
• Study Completion (Actual): January 21, 2021

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 5, 2016
• First Posted (Estimated): August 11, 2016

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Functional Neuroimaging; Transcranial Magnetic Stimulation, Repetitive; Individualized Medicine; Transcranial Direct Current Stimulation Monocentric; Compariative Cross-Over 3 Arms Study Randomized, Single-Blind Method
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Therapeutics; Behavioral Disciplines and Activities; Magnetic Field Therapy; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation
• Other Study ID Numbers: 6194

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO