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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03040388
• Other study ID #: DK-ECT-MR-1
• Status: Completed
• Start date: August 9, 2017
• Est. completion date: June 11, 2020

Study information

• Verified date: September 2020
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: June 11, 2020
• Est. primary completion date: October 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease

Locations

Country	Name	City	State
Denmark	Mental Health Centre Glostrup	Glostrup	The Capital Region

Sponsors (5)

Lead Sponsor	Collaborator
University of Copenhagen	Glostrup University Hospital, Copenhagen, Mental Health Centre Amager, Mental Health Centre Copenhagen, Mental Health Centre Glostrup

Country where clinical trial is conducted

Denmark, 

References & Publications (55)

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* Note: There are 55 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Volumetric changes in the hippocampus.	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)
Primary	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)
Primary	Changes in regional cerebral blood flow (rCBF) in the frontal lobes.	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	The number of WMLs in the brain.	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)
Secondary	Changes in water diffusion in the brain.	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)
Secondary	Changes in the level of fractional anisotropy (FA) in the brain.	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)
Secondary	Changes in the level of intrinsic connectivity pattern in fronto-limbic pathways in the brain.	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)
Secondary	Changes in the glucose metabolism in the brain.	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)
Secondary	Changes in blood-brain barrier (BBB) permeability.	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)
Secondary	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)

External Links

•   Dansk Psykiatrisk Selskab: ECT-behandling. Videnskabelig rapport og klinisk vejledning. 2011
•   Ottosson J-O, Fink M. Ethics in electroconvulsive therapy. New York: Brunner-Reoutledge, 2004.
•   Sundhedsstyrelsen: Referenceprogram for Unipolar Depression hos voksne. 2007.