Bipolar Disorder (BD)EPICNCT07404085
Epigenetic Enhancement of Cognitive Training in Aging Mood and Schizophrenia Spectrum Disorder Populations
A study testing Virtual Reality-based cognitive remediation therapy (VR-CRT) and HDACi butyrate in people with Bipolar Disorder (BD) and Depression - Major Depressive Disorder, run by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital at 1 site in Denmark.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Bipolar Disorder (BD), Depression - Major Depressive Disorder, Cognitive Impairment
- What is being tested?
- Virtual Reality-based cognitive remediation therapy (VR-CRT) and HDACi butyrate
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteDenmark
- Study dates
- 14 Nov 2025to 1 Jul 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed ICD-10 diagnosis of BD or recurrent UD in partial, or full remission (Hamilton Depression Rating Scale-17 items and Young Mania Rating Scale scores ≤14) or SSD assessed relatively stable by primary clinician at time of inclusion.
- Subjective cognitive complaints (self-reported: COBRA ≥12) or objectively-verified cognitive impairment (measured using Screening for Cognitive Impairment in Psychiatry SCIP: total score or at least two subscores ≥ 0.5 SD below expected norms)
- Fluency in Danish language
Who cannot join
- Neurological disorders (including dementia)
- Dyslexia
- Severe Physical illness
- Kidney disease
- Cardiovascular disease
- Diabetes
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- Alcohol or substance abuse
- Previous severe head trauma
- History of epilepsy
- Pregnancy or breastfeeding
- BMI >35
- Bodyweight < 45kg
- Daily use of benzodiazepines > 22.5 mg. oxazepam or > 7.5 mg. diazepam per day
- Serum lithium levels > 0.8 mmol/L
- Received electroconvulsive therapy < 2 months prior to participation
- Hypertension (>140 systolic or > 90 diastolic mm Hg)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Bjørn Ole Barkholt Nordseth, Ph.D.-student contact
Denmark1 site, 1 recruiting
- Recruiting
Neurocognition and Emotion Across Disorders (NEAD Brain Centre, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Frederiksberg Hospital
Frederiksberg, Capital Region of Denmark, 2000
Kamilla Woznica Miskowiak, DMSc, DPhil, +4522771617, kamilla.woznica.miskowiak@regionh.dk
About this study
Official title: Epigenetic Priming to Enhance Cognitive Training Gains and Neuroplasticity in Middle-age and Older Adults With Mood or Schizophrenia Spectrum Disorders (EPIC)
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.
Read more
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.
Read the detailed description
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).
- Conditions
- Bipolar Disorder (BD), Depression - Major Depressive Disorder, Cognitive Impairment, Schizophrenia Disorders
- Being tested
- Virtual Reality-based cognitive remediation therapy (VR-CRT), Virtual Reality-based control treatment (VR-CT), HDACi butyrate, Placebo
- Keywords
- Cognition, Cognitive impairment, Mood disorders, Cognitive decline, Neuroplasticity, Schizophrenia spectrum disorders
- Medical subject headings
- Bipolar Disorder, Cognitive Dysfunction, Schizophrenia, Mood Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Virtual Reality-based cognitive remediation therapy (VR-CRT)Behavioural
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.
Virtual Reality-based control treatment (VR-CT)Behavioural
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.
HDACi butyrateDietary supplement
Daily intake of sodium butyrate.
PlaceboDietary supplement
Daily intake of placebo.
| Study group | Role | What they receive |
|---|---|---|
| Group 1/4: VR high intensity + sodium butyrate | Experimental | 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. Receives: Behavioral: Virtual Reality-based cognitive remediation therapy (VR-CRT); Dietary Supplement: HDACi butyrate |
| Group 2/4: VR high intensity + placebo | Active comparator | VR high intensity (VR-CRT): Same as above.
In this arm, VR high intensity (VR-CRT) is combined with placebo. Receives: Behavioral: Virtual Reality-based cognitive remediation therapy (VR-CRT); Dietary Supplement: Placebo |
| Group 3/4: VR low intensity + sodium butyrate | Sham comparator | 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. Receives: Behavioral: Virtual Reality-based control treatment (VR-CT); Dietary Supplement: HDACi butyrate |
| Group 4/4: VR low intensity + placebo | Sham comparator | VR low intensity (VR-CT): Same as above.
In this arm, VR-based control treatment (VR-CT) is combined with placebo. Receives: Behavioral: Virtual Reality-based control treatment (VR-CT); Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, week 4 (treatment completion. Primary outcome assessment time point) and week 8 (follow-up)
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Baseline, week 4 (treatment completion) and week 8 (follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study start14 Nov 2025
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar Disorder (BD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kamilla Woznica Miskowiak, Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
- Investigators
- Kamilla Woznica Miskowiak, DMSc, DPhil, Principal investigator, Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg HospitalJulian Macoveanu, PhD, Study director, Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07404085
- Sponsor's protocol ID
- H-25020884
- Other IDs
- P-2025-18923
- Acronym
- EPIC
- Status last verified
- Feb 2026
- First submitted
- 11 Dec 2025
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No