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

September 21, 2020 updated by: Poul Videbech, University of Copenhagen

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

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

26

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • The Capital Region
      • Glostrup, The Capital Region, Denmark, 2600
        • Mental Health Centre Glostrup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 95 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population consists of the inpatients admitted to one of the recruiting Mental Health Centres (MHC) in the Capital Region of Denmark (Mental Health Centre Glostrup or Amager or Copenhagen or others), diagnosed with either depression according to the 10th version of the International Classification of Diseases (ICD-10) or major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV) and scheduled to ECT series.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Volumetric changes in the hippocampus.
Time Frame: 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).
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 BDNF concentration in the blood.
Time Frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
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.
Time Frame: 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.
at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of WMLs in the brain.
Time Frame: 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.
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 water diffusion in the brain.
Time Frame: 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.
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 the level of fractional anisotropy (FA) in the brain.
Time Frame: 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.
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 the level of intrinsic connectivity pattern in fronto-limbic pathways in the brain.
Time Frame: 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.
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 the glucose metabolism in the brain.
Time Frame: 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.
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 blood-brain barrier (BBB) permeability.
Time Frame: 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.
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 S100B-protein concentration in the blood.
Time Frame: at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)
at 3 time points: at baseline (before ECT series), after an ECT series (+3 day), at follow-up (6 months after the ECT series)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Copenhagen

Collaborators

Glostrup University Hospital, Copenhagen
Mental Health Centre Copenhagen
Mental Health Centre Glostrup
Mental Health Centre Amager

Investigators

  • Principal Investigator: Poul Videbech, Professor, Mental Health Centre Glostrup

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 9, 2017

Primary Completion (ACTUAL)

October 30, 2019

Study Completion (ACTUAL)

June 11, 2020

Study Registration Dates

First Submitted

January 30, 2017

First Submitted That Met QC Criteria

February 1, 2017

First Posted (ESTIMATE)

February 2, 2017

Study Record Updates

Last Update Posted (ACTUAL)

September 22, 2020

Last Update Submitted That Met QC Criteria

September 21, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DK-ECT-MR-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to share Individual Patient Data.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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