Clinical trial NCT06391723: Clinical, Cognitive and Neural Effects of Potentiation of ECT by rTMS in Treatment-Resistant Depression
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Major Depressive Disorder
Keywords: Treatment-resistant-depression
repetitive transcranial magnetic stimulation (rTMS)
electroconvulsive therapy (ECT)
combination of neurostimulation techniques
Lead sponsor: Centre Hospitalier du Rouvray
Sponsor class: OTHER_GOV
Collaborators: name: University Hospital, Rouen
name: Centre Hospitalier Sainte Anne, Paris
First posted: 2024-04-30
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized, double-blind, sham-controlled trial
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Response rate after 10 ECT
timeFrame: Day 0 and Day 40
Secondary outcomes:
measure: The relative improvement of depressive symptoms throughout the study (assessed by a clinician)
timeFrame: Day 0, Day 4, Day 19, Day 26, Day 40
measure: The relative improvement of depressive symptoms throughout the study (self-reported)
timeFrame: Day 0, Day 4, Day 19, Day 26, Day 40
measure: Adverse effects
timeFrame: Day 4, Day 19, Day 26, Day 40
measure: Subjective assessment of memory
timeFrame: Day 4, Day 19, Day 26, Day 40
measure: Subjective assessment of cognitive functioning
timeFrame: Day 4, Day 19, Day 26, Day 40
measure: Global cognitive functioning (objective)
timeFrame: Day 0 and Day 40
measure: Verbal memory performances (objective)
timeFrame: Day 0 and Day 40
measure: Attention (objective)
timeFrame: Day 0 and Day 40
measure: Visuospatial and constructional ability (objective)
timeFrame: Day 0 and Day 40
measure: Autobiographical memory (objective)
timeFrame: Day 0 and Day 40
measure: Seizure threshold
timeFrame: Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37
measure: Seizure duration
timeFrame: Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37
measure: Postictal Suppression
timeFrame: Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37
measure: Dose of medication
timeFrame: Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37
measure: Changes in regional gray matter density
timeFrame: Day 0 and Day 40
measure: Changes in cortical thickness
timeFrame: Day 0 and Day 40
measure: Brain activity and biochemical changes
timeFrame: Day 0 and Day 40
Other outcomes:
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