An interventional study of Virtual Reality-based cognitive remediation therapy (VR-CRT) and Virtual Reality-based control treatment (VR-CT) in Bipolar Disorder (BD), Depression - Major Depressive Disorder and Cognitive Impairment, sponsored by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital. Recruiting at 1 site in Denmark. Open to participants aged 35 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-10-07.
Sponsored by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital · Not applicable, Interventional, and Treatment
The aim of this clinical trial is to investigate the effects of a three-week virtual reality-based cognitive remediation training (VR-CRT) programme in combination with daily intake of a histone deacetylase inhibitor (HDACi) sodium butyrate on cognition in symptomatically stable patients with mood (depression or bipolar disorder; MD) or schizophrenia spectrum disorders.
The investigators hypothesize that the VR-based cognitive remediation training (VR-CRT) combined with HDACi butyrate vs. a VR-based control treatment combined with placebo will improve global cognition (primary outcome measure) over three weeks.
Secondly, the investigators hypothesize that VR-CRT with placebo will improve cognition relative to the VR control treatment with placebo, although to a lesser extent than VR-CRT with HDACi butyrate.
Thirdly, the investigators hypothesize that the HDACi butyrate with VR control treatment will not produce cognitive improvements relative to placebo with VR control treatment.
Finally, the investigators hypothesize that the combined treatment (VR-CRT + HDACi butyrate) will enhance neuroplasticity (exploratory outcome) vs. VR control with placebo, as indicated by increase in hippocampal volume and/or memory-related activity shown with structural and functional MRI.
The present study will include middle-age to older (35-75) outpatients with mood (major depressive disorder or bipolar disorder) or schizophrenia spectrum disorders (F20-spectrum) in full or partial remission (symptomatically stable) or mild depression at the time of inclusion (≤ 18 on the Hamilton Depression Rating Scale - HDRS-17 and ≤ 14 on the Young Mania Rating Scale - YMRS). To accommodate an approximated drop-out rate of 15% from baseline to treatment completion (primary outcome assessment time point), the investigators will recruit up to 160 participants until full data sets are obtained for 120 participants (30 participants per arm).
Recruitment will be carried out through the outpatient Copenhagen Affective Disorder Clinic, other mental health centers in the Capital Region of Denmark, through consultant psychiatrists in the Capital Region and through advertisements on relevant websites.
After inclusion, baseline assessments are scheduled and completed over two days, one to five days apart. Participants are assessed with a VR-based virtual cognition test (CAVIR), and a comprehensive neuropsychological cognitive test battery. Participants also complete questionnaires concerning subjective cognitive complaints, quality of life, and personality traits. Psychosocial functioning is assessed using a clinician-rated interview and a performance-based assessment. Finally, sleep quantity and quality in the past 3 days is recorded. Within +/- 3 days an fMRI scan is carried out encompassing a spatial working memory N-back task, a word encoding paradigm in which participants encode and recall words of typical household items, an affective picture encoding test, in which participants denote the orientation (left/right) of emotionally valent pictures (incidental encoding), resting state, and a structural scan. After the scan, participants are asked to recall the emotional pictures encoded during the scan.
The virtual reality cognition test, neuropsychological assessments, questionnaires, clinical symptom ratings, assessment of psychosocial functioning and fMRI scan are repeated within 2 weeks of treatment completion (primary outcome assessment time). All assessments but fMRI are repeated again 1 month (4 weeks) after treatment completion.
Block randomization is 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 ≥ 60 years) and diagnosis (major depressive disorder or bipolar disorder).
1,683 studies on the registry are indexed under Bipolar Disorder; 266 are open to participants now.
This study's planned enrollment of 160 is above the median of 64 across 1,279 interventional studies indexed under Bipolar Disorder.
Browse Bipolar Disorder studies →Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital is the lead sponsor of 19 studies on the registry; 7 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Oct 7, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
VR high intensity: Virtual reality Based Cognitive Remediation Therapy (VR-CRT). The cognitive remediation programme has a duration of three weeks and involves weekly virtual reality-based cognitive training sessions with a therapist accompanied by additional between session homework assignments consisting of cognitively challenging daily life tasks. In this arm, VR high intensity (VR-CRT) is combined with daily intake of HDACi sodium butyrate.
Behavioral: Virtual Reality-based cognitive remediation therapy (VR-CRT) · Dietary Supplement: HDACi butyrate
VR high intensity (VR-CRT): Same as above. In this arm, VR high intensity (VR-CRT) is combined with placebo.
Behavioral: Virtual Reality-based cognitive remediation therapy (VR-CRT) · Dietary Supplement: Placebo
VR low intensity: A virtual reality-based control treatment (VR-CT). This alternate treatment programme also has a duration of three weeks and involves one weekly 2-hour session with a therapist. In this arm, VR-based control treatment (VR-CT) is combined with daily intake of HDACi sodium butyrate.
Behavioral: Virtual Reality-based control treatment (VR-CT) · Dietary Supplement: HDACi butyrate
VR low intensity (VR-CT): Same as above. In this arm, VR-based control treatment (VR-CT) is combined with placebo.
Behavioral: Virtual Reality-based control treatment (VR-CT) · Dietary Supplement: Placebo
VR-CRT on 360° Meta Quest 2-software in which participants train cognitive abilities guided by a therapist. The platform includes three immersive scenarios: (1) a kitchen scenario focusing on planning and cooking a meal, (2) a supermarket scenario focusing on grocery shopping and (3) a restaurant scenario focusing on remembering names and personal information. The virtual reality training is supported by a psychoeducation program that focuses on application of learned cognitive strategies in daily life.
VR-CT: The virtual reality control training involves completing different virtual reality games that are available through the Meta 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.
Daily intake of sodium butyrate.
Daily intake of placebo.
Cognitive composite measure
A global composite score based on the neuropsychological test across several cognitive domains: the Rey Auditory Verbal Learning Test (RAVLT)66 (verbal learning and memory), WAIS-III Letter-Number Sequencing 67 and Spatial Working Memory Test (CANTAB, SWM) (working memory), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)68 Coding (psychomotor speed), phonemic fluency and One Touch Stockings of Cambridge (CANTAB69, OTS) (executive function), RBANS Digit Span Test and Rapid Visual Information Processing (CANTAB69 , RVP), (attention) and Emotion Recognition Task (CANTAB69, emotional processing). No score range. higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion. Primary outcome assessment time point) and week 8 (follow-up)
Verbal memory composite
A composite score of RAVLT based on three subtests: total recall, immediate recall, and delayed recall (verbal learning and memory). No score range. higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Cognition Assessment in Virtual Reality (CAVIR)
The total score on our newly developed virtual reality-based daily-life real-world functioning test, Cognition Assessment in Virtual Reality (CAVIR). CAVIR includes 5 tests of verbal memory, executive functions, processing speed, working memory and attention, respectively. No score range. higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Functional Assessment Short Test (FAST)
A semi-structured interview assessing level of psychosocial functioning. Score range 0-72. Higher scores mean a worse outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Rey Auditory Verbal Learning Test
Neuropsychological test assessing verbal memory. Outcomes include total recall (score range 0-75), immediate recall (score range 0-15), and delayed recall (score range 0-15). Higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing
Neuropsychological test assessing working memory. Score range 0-21. Higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Spatial Working Memory Test from Cambridge Cognition (CANTAB)
Computerized neuropsychological test assessing working memory. Outcomes include errors (score range 0-153, higher scores mean a worse outcome) and strategy (score range 3-26, higher scores mean a worse outcome).
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding
Neuropsychological test assessing psychomotor speed. Score range 0-89. Higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Verbal fluency with letters "S" and "D"
Neuropsychological test assessing executive functions. No score range. Higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
One Touch Stockings of Cambridge (OTS) from Cambridge Cognition (CANTAB)
Computerized neuropsychological test assessing executive functions. Outcomes include mean choices to correct (no score range, low scores mean a better outcome), problems solved on first choice (score range 1-15, higher scores mean a better outcome) and latency to correct (no score range, higher scores mean a worse outcome).
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Digit Span Test
Neuropsychological test assessing attention. Score range 0-16. Higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Rapid Visual Information Processing from Cambridge Cognition (CANTAB)
Computerized neuropsychological test assessing attention. Outcomes include signal detection (score range 0-1, higher scores mean a better outcome), probability of hit (score range 0-1, higher scores mean a better outcome), total false alarms (score range 0-546, higher scores mean a worse outcome), and latency to correct (score range 100-1900, higher scores mean a worse outcome).
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Emotion Recognition Task
Computerized neuropsychological test assessing emotion recognition. Outcomes include reaction time (no score range, higher scores mean a worse outcome) and hit rate (score range 0-1, higher scores mean a better outcome).
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA)
Questionnaire on subjective cognitive complaints. Score range 0-48. Higher scores means worse outcome
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Cognitive Difficulties in Everyday Life (CODEL)
Questionnaire on subjective cognitive complaints. Score range 0-48. Higher scores means worse outcome
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Hamilton Depression Rating Scale (HDRS-17)
Rating inventory assessing depressive symptoms. Score range 0-52. Higher scores mean a worse outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Young Mania Rating Scale (YMRS)
Rating inventory assessing (hypo)manic symptoms. Score range 0-60. Higher scores mean a worse outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Assessment of Quality of Life (AQoL-8D)
Questionnaire assessing quality of life. Score range 33-176. Higher scores mean a worse outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
World Health Organization Quality of Life (WHOQOL-BREF)
Questionnaire assessing quality of life. Score range 26-130. Higher scores mean a better outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Work and Social Adjustment Scale (WSAS)
Questionnaire assessing occupational functioning. Score range 0-40. Higher scores mean a worse outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Sheehan's Disability Scale (SDS)
Questionnaire assessing everyday functioning. Score range 0-30. Higher scores mean a worse outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Pittsburgh Sleep Quality Index (PSQI)
Questionnaire assessing quality of sleep. Score range 0-21. Higher scores mean a worse outcome.
Time frame: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Plan to share: No
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Started Nov 2025 (actual). Primary completion is estimated for Jul 2027, 19 months after the start.
Of 352 non-industry interventional studies with no phase under Bipolar Disorder, half reached primary completion within 37 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 58. This study's planned 19 months is below that.
Counting every sponsor, half of 354 studies reached it within 37 months; a quarter within 23 and three quarters within 58.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital