Clinical trial NCT04160286: The Danish Neuropsychological Study of the Adverse Effects of ECT
Official title: The Danish Neuropsychological Study of the Adverse Effects of ECT
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Depressive Disorder
Depression
Cognitive Dysfunction
Electroconvulsive Therapy
Keywords: Hippocampus
Depression
Electroconvulsive therapy
Brain-Derived Neurotrophic Factor
Magnetic Resonance Imaging
Autobiographical memory
Cognitive side-effects
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Mental Health Centre Glostrup
First posted: 2019-11-12
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of two groups of inpatients admitted to one of the recruiting Mental Health Centres (MHC) in the Capital Region of Denmark, diagnosed with depression according to the 10th version of the International Classification of Diseases (ICD-10) and scheduled to ECT series. Patients in the other group does not received ECT and is thus a control group.

Brief summary: The main purpose of this study is to investigate the adverse cognitive side-effects of electroconvulsive therapy (ECT). The second aim is to investigate the mechanisms of effect of ECT.

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. 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.

DANSECT is a prospective, observational follow-up study with the aim of examining why cognitive side-effects of ECT occur and potentially find predictors for whom they may affect by investigating the ECT-associated cognitive disturbances, structural brain changes and clinical outcomes. Second, DANSECT examines the mechanisms of effect of ECT.

DANSECT comprises an ECT-group (30 patients) and a clinical control group (30 patients). The former consists of patients with depression receiving ECT, and the latter consists of matched patients with depression treated pharmacologically. The examinations will take place at three time-points; before, immediately after ECT or just before discharge, and 6 months after. DANSECT is a naturalistic clinical project. This means that the number of ECT sessions given to the patients in the ECT-group is up to the referring physician.

The aim of DANSECT is to investigate the cognitive side-effects of ECT. Specifically, the research project aims to examine:

1. Prevalence, extent and persistence of adverse cognitive effects following ECT.
2. Associations between neuroimaging findings and cognitive changes following ECT.
3. Predictors of adverse cognitive effects of ECT.

Hypotheses:

1. Consistency in autobiographical memories will be reduced over time in both study groups. However, the reduction will be significantly larger for the ECT patients after ECT compared to the control group. The group difference is expected to be present at both short-term and long-term.
2. Autobiographical memory deterioration is expected to correlate with volumetric changes of the hippocampi.
3. Processing speed, anterograde memory and executive functions will be temporarily deteriorated after ECT. The cognitive changes will correlate with volumetric brain changes and changes in structural connectivity.
4. Baseline atrophy, age, years of education and cognitive reserve will predict the cognitive side-effects following ECT.
5. Machine learning will reveal patterns and inference enabling the development of a predictive model of clinical and cognitive outcome after treatment with ECT, by combining neuropsychological tests, structural and functional neuroimaging (MRI) and other neurobiological measures.

In addition, the aim of DANSECT is to investigate the mechanisms of effect of ECT. The secondary aims of the project are thus to examine:

1. Clinical, biochemical and neurobiological predictors of response to ECT
2. Clinical, biochemical and neurobiological predictors of relapse of depression after ECT
3. Biochemical and neurobiological mechanisms of response to ECT

Hypotheses:

1. Smaller baseline hippocampal volume is associated with a larger post-pre reduction of depressive symptoms
2. Thinner cortical thickness predicts better clinical improvement
3. The cortisol trajectory before ECT is associated with clinical outcome
4. Elevated peripheral baseline VEGF is associated with a larger post-pre reduction of depressive symptoms
5. Baseline microRNA levels are associated with clinical outcome
6. A higher baseline structural connectivity predicts better clinical improvement
7. A larger post-ECT increase in hippocampal volume, cortical thickness, BDNF and VEGF predicts a lower risk of relapse within six months after an ECT series

Eligibility criteria: 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 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
* 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

Primary outcomes:
measure: Columbia Autobiographical Memory Interview - Short Form
timeFrame: at baseline (before ECT series)
measure: Columbia Autobiographical Memory Interview - Short Form
timeFrame: at 5 (+/- 2) days after completion of the ECT series
measure: Columbia Autobiographical Memory Interview - Short Form
timeFrame: at follow-up (6 (+/-2) months after the ECT series
Secondary outcomes:
measure: Hamilton Depression Rating Scale
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: The Screen for Cognitive Impairment for Psychiatry
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Reys complex figure task
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Trail Making Test A
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Trail Making Test B
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Digit span (WAIS-IV)
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Five Point Test
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Color-Word Interference Test (D-KEFS)
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Symbol Digit Modalities Test
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Vividness of Visual Imagery Questionnaire - Danish version
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Vocabulary (WAIS-IV)
timeFrame: at one time point: at 5 (+/- 2) days after completion of the ECT series
measure: Cognitive complaints in bipolar disorder rating assessment
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Squire Subjective Memory Questionnaire
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: Paired Associates Learning (CANTAB)
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
measure: WHO-5
timeFrame: at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Mental Health Services of the Capital Region of Denmark
Study officials:
affiliation: University of Copenhagen & Mental Health Centre Glostrup
name: Poul Videbech, Professor
role: PRINCIPAL_INVESTIGATOR
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