Clinical trial NCT06038955: Effect of Immersive Virtual Reality-based Cognitive Remediation in Patients With Mood - or Psychosis Spectrum Disorders
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bipolar Disorder
Depression
Psychotic Disorders
Cognitive Impairment
Schizophrenia
Schizotypal Disorder
Keywords: Cognition
Cognitive Impairment
Cognitive Remediation
Depression
Bipolar Disorder
Schizophrenia
Schizotypal Disorder
Psychotic Disorders
Virtual Reality
Lead sponsor: Mental Health Services in the Capital Region, Denmark
Sponsor class: OTHER
Collaborators: name: TrygFonden, Denmark
name: University of Copenhagen
name: Rigshospitalet, Denmark
First posted: 2023-09-15
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, double-blinded, parallel-group design
Primary purpose: TREATMENT

Brief 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).

Detailed 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)

Eligibility criteria: 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

Primary outcomes:
measure: Cognition Assessement in Virtual Reality (CAVIR) test: cognitive composite score
timeFrame: Baseline, treatment completion (primary outcome assessement time point) and 3-months follow-up
Secondary outcomes:
measure: Rey Auditory Verbal Learning Test (RAVLT): verbal learning and memory domain composite score
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Assessement of Motor and Process skills (AMPS)
timeFrame: Baseline, treatment completion and 3-months follow-up
Other outcomes:
measure: One Touch Stocking of Cambridge
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Spatial Working Memory test
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Rapid Visual Information Processing
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Wechsler Adult Intelligence Scale Third edition (WAIS-III) letter-number sequencing
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) Digit Span
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) Coding
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Verbal Fluency with the letter "D" and "S"
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Trail Making Test A
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Trail Making Test B
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Brief University of California, San Diego Performance-Based Skills Assessment-B (UPSA-B)
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Wisconsin Card Sorting Task
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Functional Assessment Short Test
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Cognitive Complaints in Bipolar Disorder Rating Assessement (COBRA)
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: World Health Organization Quality of Life (WHOQOL-BREF)
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Cognitive Difficulties in Everyday Life (CODEL)
timeFrame: Baseline, treatment completion and 3-months follow-up
measure: Perceived Competence Scale (PCS)
timeFrame: Baseline, treatment completion and 3-months follow-up
Locations:
city: Frederiksberg
country: Denmark
facility: Neurocognition and Emotion in Affective Disorders (NEAD) Centre, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Frederiksberg hospital
state: Capital Region Of Copenhagen
Study officials:
affiliation: Mental Health Services in the Capital Region, Denmark
name: Kamilla Woznica Miskowiak, DMSc, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.