Multimodal Magnetic Resonance Imaging-based Study of Electroconvulsive Efficacy Prediction in Adolescents With Depression: a Multicenter Prospective Cohort Study

Study Overview
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Brief Summary
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The aim of this project is to investigate the multimodal magnetic resonance brain imaging changes in adolescents with major depressive disorder (MDD) before and after electroconvulsive therapy. Development of a predictive model for the efficacy of electroconvulsive therapy in adolescent MDD.

Detailed Description
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This is a multicenter, prospective, observational study. We will divide the adolescent MDD patients into two groups according to the treatment modality as follows: Group 1 (Modified Electroconvulsive Therapy (MECT), n=60); Group 2 (Non-Modified Electroconvulsive Therapy (Non-MECT), n=60). Patients in group 1 will be treated with MECT according to standard clinical care. Group 2 will receive conventional drug therapy. A healthy control group (n=60) will also be recruited. The most modern MRI sequences examining brain structure and function are used at 4 time points: at baseline (just before MECT series), the second examination (just after MECT series) and the third and forth (follow-up) examination (3 and 6 months after MECT series). Blood, urine and feces samples and the evaluation of clinical effect and side-effects to MECT are performed at the same time points. The primary outcome for the treatment phase is the treatment remission rate and response rate. The secondary outcomes included: symptom scale, Quality of life, Sleep therapy, Symptoms of anxiety, Rumination and safety assessment.

Official Title
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Multimodal Magnetic Resonance Imaging-based Study of Electroconvulsive Efficacy Prediction in Adolescents With Depression: a Multicenter Prospective Cohort Study

Conditions
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Major Depressive Disorder, Magnetic Resonance Imaging, Electroconvulsive Therapy

Intervention / Treatment
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* Device: Modified Electroconvulsive Therapy
* Drug: Conventional pharmacotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for the modified electroconvulsive therapy (MECT) and non-modified electroconvulsive therapy (Non-MECT) groups: Age 13-18 years. Meeting a diagnosis of depression (MDD) from the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) based the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). A score of ≥40 on the Childhood Depression Rating Scale-Revised (CDRS-R). Adequate audiovisual level to be able to complete this study. Signed informed consent and signed by the subject and guardian. Healthy control group inclusion criteria. Age 13-18 years. Sufficient audio-visual level to be able to complete the study. Signed informed consent form and signed by the subject and guardian. Exclusion criteria for the modified electroconvulsive therapy (MECT) and non-modified electroconvulsive therapy (Non-MECT) groups: The presence or previous presence of a serious medical, neurological or psychiatric condition (except in patients with MDD; anxiety co-morbidity is not considered an exclusion criterion, provided that MDD is the primary diagnosis and the main reason for seeking life-saving treatment). Patients who have received electroconvulsive therapy within the last 12 months. Patients with a history of substance, drug abuse. Contraindications to anaesthesia or MRI. Lactating women or pregnant women. Left-handedness. Exclusion criteria for healthy controls: Presence or previous serious medical, neurological or psychiatric illness. Patients with a history of substance or drug abuse. Contraindications to MRI. Lactating women or pregnant women. Left-handedness.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Modified electroconvulsive therapy group<br>The adolescent MDD receiving modified electroconvulsive therapy and conventional medication. | Device: Modified Electroconvulsive Therapy<br>* MECT is performed using the Thymatron System IV (Somatics LLC, LakeBluff, IL, USA) electroconvulsive therapy (ECT) machine. Prior to ECT, all patients undergo laboratory tests such as routine blood, liver, kidney and thyroid function and an ECG and remain fasted for 12 hours. Initial treatment power is considered by age: percentage of power = age x 0.7. Stimulation power is adjusted according to seizure duration. If the seizure duration is less than 25 seconds, the energy is increased by 5% in the subsequent treatments. Anaesthesia and muscle relaxation were administered with propofol (1.5-2 mg/kg) and succinylcholine (0.5-1 mg/kg), respectively, and subjects were awakened after ECT treatment and adverse effects, such as subjective memory impairment, headache or nausea/vomiting, were recorded. Frequency of ECT treatment: 3-4 times per week for a total of 6-8 sessions<br>Drug: Conventional pharmacotherapy<br>* Conventional pharmacotherapy: SSRIs including fluoxetine, paroxetine, sertraline, cetinopram, fluvoxamine, vortioxetine, escitalopram; SNRIs including venlafaxine, duloxetine; NaSSA including mirtazapine; other antidepressants including trazodone, bupropion, agomelatine; potentiators including aripiprazole, olanzapine, quetiapine, risperidone.<br>|
| Non-modified electroconvulsive therapy group<br>The adolescent MDD receiving only conventional medication. | Drug: Conventional pharmacotherapy<br>* Conventional pharmacotherapy: SSRIs including fluoxetine, paroxetine, sertraline, cetinopram, fluvoxamine, vortioxetine, escitalopram; SNRIs including venlafaxine, duloxetine; NaSSA including mirtazapine; other antidepressants including trazodone, bupropion, agomelatine; potentiators including aripiprazole, olanzapine, quetiapine, risperidone.<br>|
| Healthy controls group<br>Healthy adolescents. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in CDRS-R (Children's Depression Rating Scale, Revised) scores | Clinical response (≥ 50% reduction in CDRS-R scores from baseline). | The treatment period was baseline, 2-4 weeks. The follow-up period was 1 month, 3 months, 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in BDI (Beck's Depression Inventory) scores | The severity of depression symptom. | The treatment period was baseline, 2-4 weeks. The follow-up period was 1 month, 3 months, 6 months. | 
| Changes in SCARED (Screen for Child Anxiety Related Disorders) scores | The severity of Anxiety symptom. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Changes in suicide risk on C-SSRS (Columbia Suicide Severity Rating Scale) scores | The severity of the suicide risk. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Changes in PSQI (Pittsburgh Sleep Quality Index) scores | Measures of sleep status. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Changes in PedsQL4.0 (The Pediatric Quality of Life Inventory 4.0) scores | Measures of children's quality of life. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Changes in CGI-S (Clinical Global Impressions-Severity Scales) scores | Measures of clinical impression severity. | Baseline of treatment period, 2-4 weeks | 
| Changes in CGI-I (Clinical Global Impressions-Improvement Scales) scores | Measures of clinical general Impression scale. | The treatment period was 2-4 weeks | 
| Changes in RSS (Ruminative Responses Scale) scores | Measures of negative thinking. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Assessment of CTQ（Childhood Trauma Questionnaire） | Measures of childhood trauma. | Baseline of treatment period | 
| Assessment of OB/VQ（Olweus Bully/Victim Questionnaire） | Measures of bully/victim problems. | Baseline of treatment period | 
| Changes in AE（Adverse Event）Scale | Measures of any untoward medical orrurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. | The treatment period was 2-4 weeks; The follow-up period was 1 month, 3 months, 6 months. | 
| Assessment of SAE（Serious Adverse Event）Scale | Measures of adverse medical events. | The treatment period was 2-4 weeks; The follow-up period was 1 month, 3 months, 6 months. | 
| Changes in THINC-it | Measures of cognition function. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Changes in functional MRI | Resting state MRI, measurement of functional connectivity. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Changes in structural MRI T1 and T2 | Measures of brain structure. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Changes in Cerebral Blood Flow | Estimated by Arterial Spin Labeling MRI. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 
| Changes in concentration of Glu and GABA in ACC | MR Spectroscopy og the ACC, measures of neuronal integrity. | Baseline of treatment period, 2-4 weeks; The follow-up period was 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adolescent MDD, MECT, Multimodal MRI