Remotely Non-invasive Brain Stimulation and Videogame to Alleviate Depression

Study Overview
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Brief Summary
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Major depressive disorder (MDD) is a common, recurrent, and frequent chronic disorder. Treatment is often challenging; up to 40% of patients do not benefit sufficiently from existing antidepressant interventions including trials of medication and psychotherapy. Up to 25% of patients manifest a chronic course of illness, resulting in a need for additional treatment options. The DiSCoVeR trial is a multi-site, double-blind, sham-controlled, proof-of concept randomized controlled trial (RCT). The study aims to investigate the feasibility and efficacy of an innovative, combined treatment approach, incorporating transcranial direct current stimulation (tDCS) along with a custom-made video game designed to enhance cognitive control in patients with major depressive disorder (MDD). Patients diagnosis of MDD receive a 6-weeks treatment with prefrontal tDCS along with an active videogame or sham tDCS + sham game for 6 weeks. Follow-up per patient is 6 weeks following treatment. Before, during and after the treatment period different assessment scales will be conducted to record neuropsychological features and the course of symptom changes.

Detailed Description
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Major Depressive Disorder (MDD) is a prevalent, seriously impairing, and often recurrent mental disorder. It has been ranked as a leading cause of disability worldwide by the World Health Organization (WHO) as measured by years lived with disability. A considerable number of patients with MDD experience a chronic course of illness and approximately one third of MDD patients do not respond sufficiently to pharmacological treatment, calling for treatment alternatives. Non-invasive brain stimulation techniques (NIBS) such as tDCS targeting prefrontal cortical areas have emerged as a safe, promising, and cost-effective alternative to traditional treatment options in patients with MDD. This study focuses not only on an overall reduction of depressive symptoms, but also an alleviation of cognitive control deficits in particular, since patients with MDD often suffer from cognitive control deficits. tDCS has been shown to directly modulate cognitive control functions in healthy participants and in depressed patients. Another approach to directly modulate cognitive control functions is cognitive control training. In the present study, an engaging and captivating cognitive control training designed as an action video game will be employed. The primary objective is to test the feasibility and efficacy of this innovative, combined treatment approach for self application, concurrently applying both interventions (tDCS + cognitive control training) in patients suffering from MDD. Additionally, participants have the opportunity to choose to take part in two adjunctive assessments: a biological assessment which includes salivary samples and a multimodal imaging paradigm (fMRI).

Official Title
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The DiSCoVeR Project: Examining the Synergistic Effects of a Cognitive Control Videogame and a Self-administered Non-invasive Brain Stimulation on Alleviating Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: active tDCS
* Device: sham tDCS
* Behavioral: cognitive and emotional control video game
* Behavioral: sham video game


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Men and woman 18-65 years of age. Primary Diagnostic and Statistical Manual (DSM-5) diagnosis of Major Depressive Disorder (MDD), with a single or recurrent episode with the additional requirement of a current episode with a duration of ≥4 weeks. Current depressive episode lasts less than 5 years (the current and previous depressive episodes are demarcated by a period of ≥2 months in which the patient did not meet full criteria for the DSM-5 definition of MDD). Total Hamilton-21 score ≥ 13 at screening visit. Capable and willing to provide informed consent. Patients without antidepressant medication or patients on an adequate (i.e., at least lowest effective) and stable (i.e., for ≥ 6 weeks) dosage of SSRI (Escitalopram, Citalopram, Sertralin, Paroxetin, Fluvoxamin, Fluoxetin), SSNRI (Duloxetin, Venlafaxin) or Others (Mirtazapin, Agomelatin, Vortioxetine) Concomitant psychotherapy is allowed if ongoing for at least 3 months prior to baseline. Exclusion Criteria: Investigators, site personnel directly affiliated with this study, and their immediate families (immediate family is defined as a spouse, parent, child or sibling, whether by birth or legal adoption). Addiction to gaming as assessed by the Gaming Disorder Test (GDT). Individuals diagnosed with the following psychiatric conditions (current unless otherwise stated): Depression assessed as secondary to a general medical condition or substance-induced Substance abuse or substance dependence (except nicotine, caffeine) in the last 6 months Psychotic disorder (lifetime) Bipolar disorder (I and II; lifetime) Eating disorder if stated as primary diagnosis Obsessive compulsive disorder if stated as primary diagnosis Post-traumatic stress disorder if stated as primary diagnosis Generalized anxiety disorder if stated as primary diagnosis Panic disorder/ social anxiety if stated as primary diagnosis Personality disorder if stated as primary diagnosis Individuals diagnosed with a significant neurological disorder or insult including, but not limited to: Increased intracranial pressure Space occupying brain lesion History of cerebrovascular accident Transient ischemic attack within two years Cerebral aneurysm, dementia Parkinson's disease Huntington's chorea Multiple sclerosis Epilepsy Electroconvulsive therapy (ECT) treatment in current episode History of tDCS, except for single tDCS sessions in experimental studies Use of any investigational drug within 6 weeks from baseline Suicidal risk based on MADRS item 10 score of 4-6 or attempted suicide in current episode Acute, unstable cardiac disease Intracranial implant or any other metal object within or near the head (excluding the mouth) that cannot be safely removed; implanted neuro-stimulators Known or suspected pregnancy (according to pregnancy test), and women of childbearing potential not using effective contraception History of seizures Treatment with deep brain stimulation or vagus nerve stimulation and/or any other intracranial implants (clips, cochlear implants) Any relevant unstable medical condition (e.g. acute, unstable cardiac disease)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active treatment<br>active tDCS (using the Neuroelectrics Starstim tCS 5G kit) and cognitive and emotional control video game | Device: active tDCS<br>* Treatment will be applied daily 5 days/week for a period of 6 weeks, which equals a tDCS stimulation for a total of 30 treatment sessions. Every treatment session consists of 30 minutes of intervention.<br>Behavioral: cognitive and emotional control video game<br>* a video game targeting cognitive and emotional control. total of 30 treatment sessions. Every treatment session consists of 30 minutes of intervention.<br>|
| Sham Comparator: Sham treatment<br>sham tDCS (using the Neuroelectrics Starstim tCS 5G kit) and non-active videogame | Device: sham tDCS<br>* sham stimulation for a total of 30 treatment sessions. Every treatment session consists of 30 minutes of intervention.<br>Behavioral: sham video game<br>* a video game which does not target cognitive control, played for total of 30 treatment sessions. Every treatment session consists of 30 minutes of intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of treatment | Feasibility is met if a patient will complete 20 sessions per protocol with a probability of more than 50.00%.Completion per protocol is achieved, if the patient completes 20 sessions per protocol with a probability of more than 50 percent. | Six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy-Improvement on the MADRS scores compared to baseline. | Change from baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) scores at week 6 post-randomization compared to baseline. The MADRS scores severity of depression on a scale from 0-60. Higher scores indicate worse depression. A total score between 0-6 indicates that the patient is in the normal range (no depression), 7-19 indicates mild depression, 20-34 indicates moderate depression, and a score of 35 and greater indicates severe depression. | six weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognitive control, non-invasive brain stimulation, transcranial direct current stimulation, VideoGame, self-application, home-based, feasibility, efficacy