Effect of Immersive Virtual Reality-based Cognitive Remediation in Patients With Mood - or Psychosis Spectrum Disorders

Depression Clinical Trial

Official title:

Effect of Immersive Virtual Reality-based Cognitive Remediation in Patients With Mood Disorders or Psychosis Spectrum Disorders: a Randomized, Controlled, Double-blinded Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06038955
• Other study ID #: H-22004153
• Secondary ID: P-2022-411
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2022
• Est. completion date: June 1, 2025

Study information

• Verified date: January 2024
• Source: Mental Health Services in the Capital Region, Denmark
• Contact: Andreas Elleby Jespersen, PhD-student
• Phone: +4528587815
• Email: andreas.elleby.jespersen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to investigate the effect of a four-weeks, intensive virtual reality (VR)-based cognitive remediation (training) programme involving simulated daily-life challenges on cognition and functional capacity in symptomatically stable patients with mood disorders (depression or bipolar disorder) or psychosis spectrum disorders (F20-F29; e.g. schizophrenia or schizotypal disorder).

The investigators hypothesize that VR-based cognitive remediation vs. a VR control treatment has a beneficial effect on cognition after four-weeks treatment completion (primary outcome assessement time) measured with a novel ecologically valid VR test of daily-life cognitive functions (The CAVIR test; primary outcome measure), a verbal learning and memory composite score based on a traditional neuropsychological test and a performance-based measure of daily functioning (secondary outcome measures). Finally, for exploratory purposes, the study will examine neuronal underpinnings of treatment effects, and effects on additional measures of cognition, functioning and self-ratings scales (tertiary outcomes).

Description:

The current study will include outpatients with a mood disorders (unipolar - or bipolar disorder) in full or partial remission at the time of inclusion (score ≤ 14 on the Hamilton Depression or a psychosis spectrum disorders (F20-F29) that have been assessed to be relatively symptom stable by their treating clinician upon referral to the study. To accommodate for an approximately 20% drop-out rate from baseline to treatment completion (the primary outcome assessement time point), the investigators will recruit up to 66 participants (33 participants per intervention arm) to obtain complete data for minimum 54 participants (27 participants per arm).

Recruitment will be carried out through the outpatient Copenhagen Affective Disorder Clinic, the outpatient, early intervention clinics for psychotic disorders (OPUS), other mental health centres in the Capital Region of Denmark, and through advertisements on relevant websites.

After inclusion, the baseline assessements are scheduled and completed over two days, one to five days apart. On day 1, the participant is assessed with the virtual cognition test (the CAVIR test) and a comprehensive neuropsychological test battery. Participants also complete questionnaires concerning subjective cognitive complaints, quality of life and general acceptance of virtual reality technology. Functional capacity is assessed using a clinician-rated interview and a performance-based assessment. For participants with mood disorders, mood symptoms are rated with the Hamilton Depression Rating Scale (HDRS-17) and Young Mania Rating Scale (YMRS). For participants with psychosis spectrum disorders, positive and negative symptoms are rated with the Scale for the Assessement of Positive symptoms (SAPS) and Brief Negative Symptom Scale (BNSS), respectively. Finally, sleep quantity and quality in the past 3 days is recorded. Later the same day an fMRI scan is carried out encompassing a spatial working memory N-back task, a word encoding paradigm in which participants must encode and subsequently recognize words of typical household items, a resting state, and a structural scan. On day 2, participants' daily life functional capacity is assessed with The Assessement of Motor and Process Skills (AMPS) by an AMPS-certified occupational therapist in a standardized test kitchen.

The virtual reality cognition test, neuropsychological assessments, questionnaires, clinical symptom ratings, assessements of functional capacity (including AMPS) and fMRI scan are repeated within 2 weeks of treatment completion (primary outcome assessement time). All assessments except for the fMRI scan are repeated again 3 months after treatment completion to assess durability.

Participants are randomized upon full completion of the baseline assessement with allocation being carried out using the automated randomization module in the online Research Electronic Data Capture (REDcap) system based on an uploaded blocked randomization list stratified by age (< or ≥ 35 years) and diagnosis (mood disorders v. psychosis spectrum disorder)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Fluent Danish skills

• Meet the International Classification of Diseases 10th edition (ICD-10) diagnosis of unipolar disorder, bipolar disorder (types I and II) or a psychosis spectrum disorder (i.e. F20-F29) confirmed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview

• Patients must have objective and subjective cognitive impairment at the time of inclusion. Objective cognitive impairment is defined a total score on the Screen for Cognitive Impairment in Psychiatry - Danish version (SCIP-D) = 0.5 standard deviations (SD) below the expected total score based on age, education, and gender or as a score = 0.5 SD below the expected score on a minimum of two out of the five subtests (verbal learning test - immediate, working memory test, verbal fluency test, verbal learning, test - delayed, and processing speed test). Subjective cognitive impairment is defined as a score = 14 on the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA).

Exclusion Criteria:

• Current drug or substance abuse

• A daily use of benzodiazepines >22.5 mg oxazepam or >7.5 mg diazepam (cutoffs for doses with limited cognitive side effects)

• Comorbid neurological disorder

• Previous serious head trauma

• Dyslexia

• Pregnancy

• Claustrophobia (fMRI scan)

• Having a pacemaker or other metal implants inside the body (fMRI scan)

• Having had electroconvulsive therapy in the 3 months prior to inclusion

Related Conditions & MeSH terms

• Bipolar Disorder
• Cognitive Dysfunction
• Cognitive Impairment
• Depression
• Mental Disorders
• Psychotic Disorders
• Schizophrenia
• Schizotypal Disorder

Intervention

Behavioral:
• Virtual reality Based Cognitive Remediation
The main component of the intervention is a virtual reality training platform in 360° Oculus Quest 2-software in which participants train their cognitive abilities guided by the therapist. The platform includes four immersive daily-life scenarios in which patients have consistently reported that they often experience cognitive difficulties: (1) a kitchen scenario focusing on planning and cooking a meal, (2) a supermarket scenario focusing on grocery shopping, (3) a restaurant scenario focusing on remembering names and personal information and (4) an office scenario focusing on planning, initiating, and completing work assignments. The virtual reality training is supported by a psychoeducation program that focuses on application of learned cognitive strategies in daily life.
• Virtual reality control training
The virtual reality control training involves completing different virtual reality games that are available through the Oculus Quest games store.The chosen games involve no direct training of cognitive abilities such as planning skills og strategic learning, but merely involves simple reaction time and interaction with an entertaining environment that is meaningful to the participant and gives the impression of training cognitive skills.

Locations

Country	Name	City	State
Denmark	Neurocognition and Emotion in Affective Disorders (NEAD) Centre, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Frederiksberg hospital	Frederiksberg	Capital Region Of Copenhagen

Sponsors (4)

Lead Sponsor	Collaborator
Mental Health Services in the Capital Region, Denmark	Rigshospitalet, Denmark, TrygFonden, Denmark, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

Miskowiak KW, Jespersen AE, Kessing LV, Aggestrup AS, Glenthoj LB, Nordentoft M, Ott CV, Lumbye A. Cognition Assessment in Virtual Reality: Validity and feasibility of a novel virtual reality test for real-life cognitive functions in mood disorders and psychosis spectrum disorders. J Psychiatr Res. 2021 Dec 12;145:182-189. doi: 10.1016/j.jpsychires.2021.12.002. Online ahead of print. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	One Touch Stocking of Cambridge	A computerised neuropsychological test assessing executive function. Score range 0-15. Higher scores mean a better outcome	Baseline, treatment completion and 3-months follow-up
Other	Spatial Working Memory test	A computerised neuropsychological test assessing spatial working memory. Score range 2-14. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up
Other	Rapid Visual Information Processing	A computerised neuropsychological test assessing sustained attention. Score range 0-1. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up
Other	Wechsler Adult Intelligence Scale Third edition (WAIS-III) letter-number sequencing	Neuropsychological test assessing executive function. Score range 0-21. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up
Other	Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) Digit Span	Neuropsychological test assessing attention. Score range 0-16. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up
Other	Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) Coding	Neuropsychological test assessing processing speed. Score range 0-89. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up
Other	Verbal Fluency with the letter "D" and "S"	Neuropsychological test assessing executive function. No score range. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up
Other	Trail Making Test A	Neuropsychological test assessing attention. Scored as time to complete. A higher time means a worse outcome.	Baseline, treatment completion and 3-months follow-up
Other	Trail Making Test B	Neuropsychological test assessing executive function. Scored as time to complete. A higher time means a worse outcome.	Baseline, treatment completion and 3-months follow-up
Other	Brief University of California, San Diego Performance-Based Skills Assessment-B (UPSA-B)	Objective assessment of level of functioning. Score range 0-100. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up
Other	Wisconsin Card Sorting Task	Computerized neuropsychological test assessing executive function. No score range. Higher scores mean a worse outcome.	Baseline, treatment completion and 3-months follow-up
Other	Functional Assessment Short Test	Observer-based rating of level of functioning. Score range 0-72. Higher scores mean a worse outcome.	Baseline, treatment completion and 3-months follow-up
Other	Cognitive Complaints in Bipolar Disorder Rating Assessement (COBRA)	Questionnaire on subjective cognitive complaints. Score range 0-48. Higher scores mean a worse outcome.	Baseline, treatment completion and 3-months follow-up
Other	World Health Organization Quality of Life (WHOQOL-BREF)	Questionnaire on quality of life. Score range 26-130. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up
Other	Cognitive Difficulties in Everyday Life (CODEL)	Questionnaire on subjective cognitive complaints. Score range 0-48. Higher scores mean a worse outcome	Baseline, treatment completion and 3-months follow-up
Other	Perceived Competence Scale (PCS)	Questionnaire on self-efficacy. Score range 0-49. Higher scores mean a better outcome	Baseline, treatment completion and 3-months follow-up
Primary	Cognition Assessement in Virtual Reality (CAVIR) test: cognitive composite score	The primary outcome measure is a broad cognitive composite score spanning all five subtasks on a novel virtual reality test of daily-life cognitive functions, the Cognition Assessement in Virtual Reality (CAVIR) test. The CAVIR test is a self-administered 360º immersive VR test in a kitchen, where the participant's abilities to plan and prepare a meal are assessed. The test has a duration of 15 minutes and involves five subtasks probing verbal memory, executive functions, processing speed, working memory and sustained attention, respectively. The cognitive composite score is calculated by averaging the z-transformed scores on the five CAVIR subtasks. No score range. Higher scores mean a better outcome.	Baseline, treatment completion (primary outcome assessement time point) and 3-months follow-up
Secondary	Rey Auditory Verbal Learning Test (RAVLT): verbal learning and memory domain composite score	A domain composite of 'verbal learning and memory' comprising the following subtests on the Rays Verbal Learning (RAVLT) Test: RAVLT total recall lists I-V, RAVLT immediate recall, RAVLT delayed recall. Score range 0-120. Higher scores mean a better outcome	Baseline, treatment completion and 3-months follow-up
Secondary	Assessement of Motor and Process skills (AMPS)	A recommended measure of functioning (i.e. Activity of Daily Living) in individuals with psychiatric illness and cognitive impairment conducted by an AMPS-certificated occupational therapist a standardized test apartment. During an AMPS-evaluation, two domains of performance are evaluated: ADL motor skills (16 items) and ADL process skills (20 items). Scoring of the AMPS assessment is conducted using t available software Occupational Therapy Assessment Package (OTAP) reporting software. OTAP is based on a many-faceted Rasch measurement model making it possible to convert ordinal raw scores into overall linear ADL motor and process ability measures adjusted for severity of the task, skill item difficulty, and rater severity (determined based on rater calibration). A clinically relevant difference has been determined as =0.3 logit on the ADL motor or process ability scales. Higher scores mean a better outcome.	Baseline, treatment completion and 3-months follow-up