Exploring Effects of Electroconvulsive Therapy on the Human Brain in Depression - The Danish ECT/MRI Study

Sponsor

University of Copenhagen (Other)

Overall Status

Completed

CT.gov ID

NCT03040388

Collaborator

Mental Health Centre Glostrup (Other), Glostrup University Hospital, Copenhagen (Other), Mental Health Centre Amager (Other), Mental Health Centre Copenhagen (Other)

Enrollment

Location

34.1

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to determine whether electroconvulsive therapy (ECT) causes any structural or functional brain changes and thus indicating its mechanism of action. The second aim is to find predictors of an immediate response, sustained remission, relapse and side-effects. Thirdly, this study aims to explore whether ECT causes any changes in blood-brain barriers permeability and whether these changes correlate to memory problems. The fourth objective is to examine whether ECT causes any brain tissue damage.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder Depression Depressive Disorder, Major

Detailed Description

ECT has been the most effective treatment of depression for decades. Despite of this, neither the mechanism of action or side-effects are fully elucidated. The reason why some patients relapse shortly after remission is still not completely understood. Thus, there is a need to find predictors of the favourable clinical effect, relapse and side-effects. ECT is considered by professionals to be a safe procedure. However, this view is based on rather old and small studies. Additionally, many patients do not consent to this treatment because they fear a permanent loss of memory or that they will contract a brain damage after the completed ECT series. Therefore, it is very important to examine whether ECT might have negative effects on the structure or function of the brain, using state of the art Magnetic Resonance Imaging (MRI) techniques on a greater study population.

The study consists of 60 inpatients, diagnosed with depression, admitted to one of the recruiting Mental Health Centres, and scheduled to ECT. The most modern MRI sequences examining brain structure and function are used at 3 time points: at baseline (just before ECT series), the second examination (just after ECT series) and the third (follow-up) examination (6 months after ECT series). Blood samples (measurements of Brain-Derived Neurotrophic Factor - BDNF, Vascular Endothelial Growth Factor - VEGF along with the marker of brain injury - S100B-protein) and the evaluation of clinical effect and side-effects to ECT are performed at the same time points.

The study has 4 main hypotheses. The first hypothesis assumes that the immediate and sustained response to ECT can be predicted by combining neuroimaging findings and blood-samples results. The second hypothesis is based on the assumption that ECT modulates the microstructure and connectivity in the fronto-limbic pathways (FLPs) and that this modulation correlates with the clinical effect. Thus, the altered microstructure of the FLPs in depression is normalised by an ECT series. Furthermore, the depression-associated increased resting state connectivity in FLPs is normalised by ECT. The third hypothesis is that ECT will induce changes in blood-brain barrier (BBB) permeability, which will correlate with the severity of memory problems. The last hypothesis assumes that ECT does not cause any brain tissue damage (including brain atrophy and white matter lesions - WMLs).

Study Design

Study Type:

Observational

Actual Enrollment :

26 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Predicting Effects and Risk of Relapse Into Depression - The Danish ECT/MRI Project

Actual Study Start Date :

Aug 9, 2017

Actual Primary Completion Date :

Oct 30, 2019

Actual Study Completion Date :

Jun 11, 2020

Outcome Measures

Primary Outcome Measures

Volumetric changes in the hippocampus. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
This outcome will be measured by means of voxel-based morphometry (VBM).
Changes in BDNF concentration in the blood. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
Changes in regional cerebral blood flow (rCBF) in the frontal lobes. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
Pseudo-continuous arterial spin-labelling (PSCAL) will be used to measure this outcome.

Secondary Outcome Measures

The number of WMLs in the brain. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
FLAIR sequences of MRI will be used to measure this outcome.
Changes in water diffusion in the brain. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
Diffusion-weighted imaging (DWI) will be used to measure this outcome.
Changes in the level of fractional anisotropy (FA) in the brain. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
Diffusion tensor imaging (DTI) will be used to measure this outcome.
Changes in the level of intrinsic connectivity pattern in fronto-limbic pathways in the brain. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
Resting state functional MRI will be used to measure this outcome.
Changes in the glucose metabolism in the brain. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
Cerebral Metabolic Rate of Oxygen ( CMRO2) will be used to measure this outcome.
Changes in blood-brain barrier (BBB) permeability. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]
Dynamic Contrast Enhanced (DCE)T1-weighted imaging will be used to measure this outcome.
Changes in S100B-protein concentration in the blood. [at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 95 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

age 18-95 years
admitted at the MHC Glostrup, MHC Amager or MHC Copenhagen (or other Mental Health Centres in the Capital Region)
fulfilling the criteria for depression according to ICD-10 and major depression according to DSM-IV and where ECT is planned.
must be able to give informed consent to participate in the study

Exclusion Criteria:

Schizophrenia or any other psychotic disorder except for psychotic depression
Dependency syndrome according to ICD-10.
Severe somatic or neurological condition (e.g. stroke) confounding results
Head trauma resulting in unconsciousness for more than 5 minutes
Severe psychotic symptoms or suicide impulses making transportation hazardous
Contraindications against MRI or Gadovist infusion
Pregnancy
Maintenance ECT or ECT received during the last 6 months
Any form of compulsory treatment
Subjects who do not consent to be informed of incidental findings that could have healthcare implications will not be scanned and can thus not be included