Clinical, Cognitive and Neural Effects of Potentiation of ECT by rTMS in Treatment-Resistant Depression (STIMAGNECT2)

Clinical, Cognitive and Neural Effect of Potentiation of Electroconvulsive Therapy (ECT) by Repetitive Transcranial Magnetic Stimulation (rTMS) at 10 ECT in Patients With Characterized Pharmacoresistant Depressive Episode

Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. In this multicenter, randomized, double-blind, sham-controlled study, our objective is to assess the priming effect of rTMS sessions before ECT on clinical, cognitive and neural response in patients with TRD.

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: Active rTMS; Device: Sham rTMS

Detailed Description

80 patients with TRD will be assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham rTMS will be administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Then, from the sixth ECT session, an rTMS session will occur the day before each ECT session. Clinical assessment, cognitive assessment and brain imaging (structural MRI, resting state functional MRI, MR spectroscopy) will take place before and after 10 ECT sessions. Clinical, cognitive and neural changes will be compared between both groups after 10 ECT sessions.

The primary outcome will be the response rate after 10 ECT, i.e. the percentage of patients who achieved a reduction of 50% or more from their initial Hamilton Depression Scale score (HAMD-21 items).

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maud Rotharmel; Phone Number: +33232956825; Email: maud.rotharmel@ch-lerouvray.fr
• Study Contact Backup: Name: Virginie Moulier; Email: virginie.moulier@ch-lerouvray.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with Major Depressive Disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria
• HAMD score ≥15
• In case of unipolar disorder: no remission after at least two different antidepressants prescribed at a dose and duration sufficient for the current episode
• In the case of bipolar disorder: no remission despite lithium at an adequate plasma level combined with lamotrigine or quetiapine monotherapy at full dose
• No change of antidepressant or mood stabilizer treatment for at least 15 days
• To be rTMS-naive
• Without benzodiazepine or antiepileptic treatment for at least 15 days
• To understand spoken and written French
• Having given their informed, written consent

Exclusion Criteria:

• Contraindication to Electroconvulsive therapy (ECT), repeated Transcranial Magnetic Stimulation (rTMS), Magnetic Resonance Imaging (MRI), anesthesia
• Patients who have received ECT in the last 6 months
• Patients suffering from poorly stabilized epilepsy, serious neurological or systemic disorders
• Patients with a serious substance use disorder (other than nicotine or caffeine) according to DSM-5 criteria
• Patients suffering from severe hearing problems
• Subjects already treated with an electrical or magnetic stimulation technique
• Women who do not have adequate contraception, pregnant or breastfeeding women
• Being deprived of liberty by an administrative or judicial decision
• Patients participating or having participated in an interventional clinical trial within 30 days before the inclusion visit

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active rTMS group; 5 active rTMS before starting ECT, then from the sixth ECT session, an active rTMS session will occur the day before each ECT session	Device: Active rTMS; rTMS will be administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session)
Placebo Comparator: Sham rTMS group; 5 sham rTMS before starting ECT, then from the sixth ECT session, a sham rTMS session will occur the day before each ECT session	Device: Sham rTMS; Sham rTMS will be administered over the left dorsolateral prefrontal cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate after 10 ECT	the percentage of patients who achieved a reduction of 50% or more from their initial Hamilton Depression Scale score (HAMD-21 items)	Day 0 and Day 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The relative improvement of depressive symptoms throughout the study (assessed by a clinician)	the relative variation of HAMD-21	Day 0, Day 4, Day 19, Day 26, Day 40
The relative improvement of depressive symptoms throughout the study (self-reported)	Quick Inventory of Depressive Symptomatology	Day 0, Day 4, Day 19, Day 26, Day 40
Adverse effects	Assessment of adverse effects with the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale adapted to rTMS (adapted UKU)	Day 4, Day 19, Day 26, Day 40
Subjective assessment of memory	Scores and variations in memory assessed with the Squire Subjective Memory Questionnaire (SSMQ)	Day 4, Day 19, Day 26, Day 40
Subjective assessment of cognitive functioning	Scores and variations in cognitive functioning assessed with the Cognitive Failures Questionnaire (CFQ)	Day 4, Day 19, Day 26, Day 40
Global cognitive functioning (objective)	Scores and variations assessed with the Mini Mental Status Examination	Day 0 and Day 40
Verbal memory performances (objective)	Scores and variations assessed with the RL/RI-16 test	Day 0 and Day 40
Attention (objective)	Scores and variations assessed the D2 test of attention	Day 0 and Day 40
Visuospatial and constructional ability (objective)	Scores and variations assessed with the Rey-Osterrieth complex figure test	Day 0 and Day 40
Autobiographical memory (objective)	Scores and variations assessed with the autobiographical memory test (TEMPau)	Day 0 and Day 40
Seizure threshold	Seizure threshold during ECT	Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37
Seizure duration	Seizure duration during ECT	Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37
Postictal Suppression	Postictal Suppression during ECT	Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37
Dose of medication	Dose of medication during ECT	Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37
Changes in regional gray matter density	Changes in regional gray matter density measured with 3D MRI	Day 0 and Day 40
Changes in cortical thickness	Changes in cortical thickness measured with 3D MRI	Day 0 and Day 40
Brain activity and biochemical changes	Changes measured with Resting state functional MRI and spectroscopy MRI	Day 0 and Day 40

Collaborators and Investigators

• Sponsor: Centre Hospitalier du Rouvray
• Collaborators: University Hospital, Rouen; Centre Hospitalier Sainte Anne, Paris

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: repetitive transcranial magnetic stimulation (rTMS); electroconvulsive therapy (ECT); Treatment-resistant-depression; combination of neurostimulation techniques
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 2023-A01813-42

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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