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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03040388
Other study ID # DK-ECT-MR-1
Secondary ID
Status Completed
Phase
First received
Last updated
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
Health authority
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

Study Design


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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Jorgensen A, Magnusson P, Hanson LG, Kirkegaard T, Benveniste H, Lee H, Svarer C, Mikkelsen JD, Fink-Jensen A, Knudsen GM, Paulson OB, Bolwig TG, Jorgensen MB. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression. Acta Psychiatr Scand. 2016 Feb;133(2):154-164. doi: 10.1111/acps.12462. Epub 2015 Jul 3. — View Citation

Joshi SH, Espinoza RT, Pirnia T, Shi J, Wang Y, Ayers B, Leaver A, Woods RP, Narr KL. Structural Plasticity of the Hippocampus and Amygdala Induced by Electroconvulsive Therapy in Major Depression. Biol Psychiatry. 2016 Feb 15;79(4):282-92. doi: 10.1016/j.biopsych.2015.02.029. Epub 2015 Mar 5. — View Citation

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Lyden H, Espinoza RT, Pirnia T, Clark K, Joshi SH, Leaver AM, Woods RP, Narr KL. Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression. Transl Psychiatry. 2014 Apr 8;4:e380. doi: 10.1038/tp.2014.21. — View Citation

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Nobler MS, Oquendo MA, Kegeles LS, Malone KM, Campbell CC, Sackeim HA, Mann JJ. Decreased regional brain metabolism after ect. Am J Psychiatry. 2001 Feb;158(2):305-8. — View Citation

Nobuhara K, Okugawa G, Minami T, Takase K, Yoshida T, Yagyu T, Tajika A, Sugimoto T, Tamagaki C, Ikeda K, Sawada S, Kinoshita T. Effects of electroconvulsive therapy on frontal white matter in late-life depression: a diffusion tensor imaging study. Neuropsychobiology. 2004;50(1):48-53. — View Citation

Nordanskog P, Dahlstrand U, Larsson MR, Larsson EM, Knutsson L, Johanson A. Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study. J ECT. 2010 Mar;26(1):62-7. doi: 10.1097/YCT.0b013e3181a95da8. — View Citation

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Palmio J, Huuhka M, Laine S, Huhtala H, Peltola J, Leinonen E, Suhonen J, Keränen T. Electroconvulsive therapy and biomarkers of neuronal injury and plasticity: Serum levels of neuron-specific enolase and S-100b protein. Psychiatry Res. 2010 May 15;177(1-2):97-100. doi: 10.1016/j.psychres.2009.01.027. Epub 2010 Apr 8. — View Citation

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* Note: There are 55 references in allClick 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)
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