The Neurobiological Fundaments of Depression and Its Relief Through Neurostimulation Treatments

Recruiting

• Conditions: Major Depressive Disorder; Major Depressive Disorder 1; Healthy
• Interventions: Device: Electroconvulsive therapy; Device: rTMS

• Registration Number: NCT05135897
• Lead Sponsor: Haukeland University Hospital

Brief Summary

The study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS).

Detailed Description

As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT and TMS

Sample, three groups:

ECT: n = 50 patients in a major depressive episode (bipolar and major depressive disorder) who have accepted treatment with ECT.

TMS: n = 50 patients in a major depressive episode (bipolar and major depressive disorder) who have accepted treatment with TMS.

HC: = 50 age and gender matched healthy volunteers not receiving ECT nor TMS.

Observation time: six months, with the time points as specified below. ECT is typically given three times weekly, but exceptions may occur. Hence, time points are specified as the number of ECT treatments given rather than an exact number of days which will vary.

Tp1: 2 hours before the first treatment session (day 1, baseline), Tp2: 2 hours after the first treatment session (day 1), Tp3: before the 7th ECT session and corresponding time point for TMS (\~ day 15), Tp4: 1-2 weeks after last treatment session (\~ day 30 - 50), Tp5: 6 months after treatment (\~ day 180),

Healthy controls are only assessed at Tp1,2,4,5

Study Timeline

• Study Start: 2021-09-27
• Status Verified: 2021-10
• Study First Submitted: 2021-10-08
• Study First Submitted QC: 2021-11-16
• Last Update Submitted: 2021-11-16
• Study First Posted: 2021-11-26
• Last Update Posted: 2021-11-26
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

ECT:

• Patients (>18) referred to the center of ECT and accepted for treatment
• because of moderate and severe depression
• fulfilling the criteria for the following ICD-10 diagnosis: F 31.3 and F31.4; F32.1 and F32.2 and F32.3; F33.1 and F33.2 and F33.3.
• In addition, the symptom intensity must be verified by a MADRS score ≥ 25.
• There is no upper age for participation, however, the responsible clinician will consider if patients are eligible for inclusion (functioning, enabled to give informed consent).

TMS:

• Patients (>18) referred to the center of TMS and accepted for treatment
• because of moderate and severe depression
• fulfilling the criteria for the following ICD-10 diagnosis: F 31.3 and F31.4; F32.1 and F32.2 and F32.3; F33.1 and F33.2 and F33.3.
• In addition, the symptom intensity must be verified by a MADRS score ≥ 25.
• There is no upper age for participation, however, the responsible clinician will consider if patients are eligible for inclusion (functioning, enabled to give informed consent).

Healthy controls:

• Age and gender matched (to the patient groups).
• No history of psychiatric illness and no current depression.
• No contraindication for MRI scanning.

Exclusion Criteria

• ECT / TMS treatment within the last 12 months.
• Patients unable to give informed consent (according to the responsible clinician or ECT / TMS responsible).
• Patients who cannot participate in the MR scanning

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients, depression, ECT	Electroconvulsive therapy	Patients in major depressive episode undergoing ECT
Patients, depression, TMS	rTMS	Patients in major depressive episode undergoing TMS

Primary Outcome Measures

Name	Time	Method
Change in Cerebral Blood Flow from baseline	Baseline, day1 (after 1 ECT), ~ day 15 (after 6 ECTs), ~ day 30 - 50 (1-2 weeks after last ECT), ~ day 180 (6 months after treatment)	Estimated by Arterial Spin Labeling MRI
Change in MADRS from baseline	Baseline, day1 (after 1 ECT), ~ day 15 (after 6 ECTs), ~ day 30 - 50 (1-2 weeks after last ECT), ~ day 180 (6 months after treatment)	Depression rating by MADRS score

Secondary Outcome Measures

Name	Time	Method
Changes in functional MRI	Baseline, day1 (after 1 ECT), ~ day 15 (after 6 ECTs), ~ day 30 - 50 (1-2 weeks after last ECT), ~ day 180 (6 months after treatment)	Resting state MRI, measurement of functional connectivity
Change in performance on test of spatial navigation	Baseline, day1 (after 1 ECT), ~ day 15 (after 6 ECTs), ~ day 30 - 50 (1-2 weeks after last ECT), ~ day 180 (6 months after treatment)	Neurocognitive assessments of spatial navigation
Change fraction of in Isotropic hindered water	Baseline, day1 (after 1 ECT), ~ day 15 (after 6 ECTs), ~ day 30 - 50 (1-2 weeks after last ECT), ~ day 180 (6 months after treatment)	Measured by Restriction spectrum imaging. Increase in the fraction of isotropic hindered water as a sign of oedema / disruptive effects of ECT seen on Imaging at 2 hours after first ECT.
Changes in structural MRI T1 and T2 and RSI	Baseline, day1 (after 1 ECT), ~ day 15 (after 6 ECTs), ~ day 30 - 50 (1-2 weeks after last ECT), ~ day 180 (6 months after treatment)	Measures of brain structure
Change in concentration of NAA, Choline, myo Inositol	Baseline, day1 (after 1 ECT), ~ day 15 (after 6 ECTs), ~ day 30 - 50 (1-2 weeks after last ECT), ~ day 180 (6 months after treatment)	MR Spectroscopy og the amygdala, measures of neuronal integrity.

Trial Locations

Locations (1)

Haukeland University Hospital; 🇳🇴 Bergen, Vestland, Norway