Remotely Non-invasive Brain Stimulation and Videogame to Alleviate Depression

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04953208
• Other study ID #: 388-20-HMO
• Status: Recruiting
• Phase: N/A
• Start date: June 22, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: Hebrew University of Jerusalem
• Contact: Mor Nahum, PhD
• Phone: 0547326655
• Email: mor.nahum[@]mail.huji.ac.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 (structural and functional sequences, including an interleaved TMS-fMRI paradigm).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Device:
• active tDCS
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.
• sham tDCS
sham stimulation for a total of 30 treatment sessions. Every treatment session consists of 30 minutes of intervention.

Behavioral:
• cognitive and emotional control video game
a video game targeting cognitive and emotional control. total of 30 treatment sessions. Every treatment session consists of 30 minutes of intervention.
• sham video game
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.

Locations

Country	Name	City	State
Germany	Ludwig-Maximilian University	Munich
Israel	Hadassah University Hospital	Jerusalem
Latvia	Riga Stradins University (RSU)	Riga

Sponsors (4)

Lead Sponsor	Collaborator
Mor Nahum	Hadassah Medical Organization, Ludwig-Maximilians - University of Munich, Riga Stradins University

Countries where clinical trial is conducted

Germany,  Israel,  Latvia, 

References & Publications (9)

Bavelier D, Green CS. Enhancing Attentional Control: Lessons from Action Video Games. Neuron. 2019 Oct 9;104(1):147-163. doi: 10.1016/j.neuron.2019.09.031. — View Citation

Brunoni AR, Moffa AH, Sampaio-Junior B, Borrione L, Moreno ML, Fernandes RA, Veronezi BP, Nogueira BS, Aparicio LVM, Razza LB, Chamorro R, Tort LC, Fraguas R, Lotufo PA, Gattaz WF, Fregni F, Bensenor IM; ELECT-TDCS Investigators. Trial of Electrical Direc — View Citation

Calkins AW, McMorran KE, Siegle GJ, Otto MW. The Effects of Computerized Cognitive Control Training on Community Adults with Depressed Mood. Behav Cogn Psychother. 2015 Sep;43(5):578-89. doi: 10.1017/S1352465814000046. Epub 2014 Mar 3. — View Citation

De Raedt R, Koster EH. Understanding vulnerability for depression from a cognitive neuroscience perspective: A reappraisal of attentional factors and a new conceptual framework. Cogn Affect Behav Neurosci. 2010 Mar;10(1):50-70. doi: 10.3758/CABN.10.1.50. — View Citation

Hoorelbeke K, Koster EHW. Internet-delivered cognitive control training as a preventive intervention for remitted depressed patients: Evidence from a double-blind randomized controlled trial study. J Consult Clin Psychol. 2017 Feb;85(2):135-146. doi: 10.1 — View Citation

Padberg F, Bulubas L, Mizutani-Tiebel Y, Burkhardt G, Kranz GS, Koutsouleris N, Kambeitz J, Hasan A, Takahashi S, Keeser D, Goerigk S, Brunoni AR. The intervention, the patient and the illness - Personalizing non-invasive brain stimulation in psychiatry. — View Citation

Padberg F, Kumpf U, Mansmann U, Palm U, Plewnia C, Langguth B, Zwanzger P, Fallgatter A, Nolden J, Burger M, Keeser D, Rupprecht R, Falkai P, Hasan A, Egert S, Bajbouj M. Prefrontal transcranial direct current stimulation (tDCS) as treatment for major dep — View Citation

Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N E — View Citation

Wolkenstein L, Plewnia C. Amelioration of cognitive control in depression by transcranial direct current stimulation. Biol Psychiatry. 2013 Apr 1;73(7):646-51. doi: 10.1016/j.biopsych.2012.10.010. Epub 2012 Dec 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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