Clinical trial NCT02667353: Neurorestorative Effects of Electroconvulsive Therapy (ECT) in Patients With Severe Late Life Depression
Official title: Structural Brain Plasticity in Elderly Depressed Patients Following Electroconvulsive Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Keywords: electroconvulsive
hippocampus
elderly
working mechanism
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: VU University of Amsterdam
First posted: 2016-01-28
Enrollment: 110
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: To study the potential neurorestorative effects of electroconvulsive therapy (ECT) in depressed patients by measuring brain derived neurotrophic factor (BDNF) serum levels and hippocampal volumes in severely depressed patients receiving ECT.

Detailed description: The investigators want to study the potential neurorestorative effects of electroconvulsive therapy (ECT) in depressed patients by measuring brain derived neurotrophic factor (BDNF) serum levels and hippocampal volumes in severely depressed patients receiving ECT.

Clinical studies in severely depressed patients have shown that antidepressants and ECT can increase Brain Derived Neurotrophic Factor (BDNF) serum levels. BDNF serum levels will be measured before, during and after ECT. In animal studies this increase in serum BDNF was shown to induce hippocampal mossy fiber sprouting and the investigators want to study this phenomenon in humans. Recently, a volumetric magnetic resonance imaging study showed increased hippocampal volume in patients with depression. Hippocampal volumes will be determined with magnetic resonance imaging scannings including voxel based morphometry. Severe depression is accompanied by a dysfunction of the hypothalamus pituitary adrenal (HPA) axis. Cortisol and several other hormones have psychotropic effects, and their excesses or deficiencies induce states of mania or depression. High levels of cortisol suppress hippocampal neurogenesis. Animal models have shown that this suppressive effect of cortisol on hippocampal neurogenesis could be reversed to normal levels by electroconvulsive stimulation, the animal model for ECT. This animal study is in good accordance with clinical findings.

The investigators hypothesize the following: Increase of brain-derived neurotrophic factor serum levels induced by electroconvulsive therapy are associated with remission and is correlated with a neurorestorative effect, which is an increase of hippocampal volume. Non- response to ECT is explained by either low BDNF serum levels regardless of hippocampus size, or by (more advanced) medial temporal lobe atrophy (beyond a point of no return) despite increased BDNF serum levels.

Additionally, four relevant functional candidate genes will be examined, based on their putative role in neurotrophic processes and/or in treatment response in depression: the brain derived neurotrophic factor gene, the serotonin transporter gene, the vascular endothelial growth factor gene and the apolipoprotein gene.

The investigators will also evaluate cognitive and psychomotor changes following electroconvulsive therapy given their clinical relevance in late life depression.

Eligibility criteria: Inclusion Criteria:

* Patients are considered suitable after they were diagnosed as having severe depression according to Diagnostic and Statistical Manual IV (DSM-IV criteria) and were above 55 years of age.

Exclusion Criteria:

* another major psychiatric illness, (a history of) a major neurological illness (including Parkinson's disease, stroke, and dementia) and metal implants precluding Magnetic Resonance Imaging (MRI).

Subjects were included at the University Psychiatric Center Katholieke Universiteit Leuven (KU Leuven), Belgium and Geestelijke Gezondheidszorg in Geest (GGZinGeest), Amsterdam, the Netherlands. The project is part of the project Mood Disorders in Elderly and Electroconvulsive therapy (MODECT).

Primary outcomes:
measure: change in hippocampal volume as assessed by manual delineation following an initial automatic segmentation
timeFrame: 6 months
measure: change in brain derived neurotrophic factor as assessed by the Emax Immuno Assay system
timeFrame: 4 weeks
measure: change of mood as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: up to 1 year
Secondary outcomes:
measure: change of cognition as assessed by the mini mental state examination
timeFrame: up to 1 year
measure: change of psychomotor symptoms as assessed by the CORE (not an acronym)
timeFrame: up to 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Mathieu Vandenbulcke, MD PhD
role: STUDY_DIRECTOR
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