Epigenetic Enhancement of Cognitive Training in Aging Mood Disorder Populations

NCT07404085 | Recruiting

• 2 other identifiers: H-25020884P-2025-18923
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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 disorders (depression or bipolar disorder). 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.

Conditions

Bipolar Disorder (BD); Depression - Major Depressive Disorder; Cognitive Impairment

Keywords

Cognition; Cognitive impairment; Mood disorders; Cognitive decline; Neuroplasticity

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, week 4 (treatment completion. Primary outcome assessment time point) and week 8 (follow-up)

Secondary Outcomes (3)

• Verbal memory composite

  Baseline, week 4 (treatment completion) and week 8 (follow-up)

• Cognition Assessment in Virtual Reality (CAVIR)

  Baseline, week 4 (treatment completion) and week 8 (follow-up)

• Functional Assessment Short Test (FAST)

  Baseline, week 4 (treatment completion) and week 8 (follow-up)

Other Outcomes (18)

• Rey Auditory Verbal Learning Test

  Baseline, week 4 (treatment completion) and week 8 (follow-up)

• Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing

  Baseline, week 4 (treatment completion) and week 8 (follow-up)

• Spatial Working Memory Test from Cambridge Cognition (CANTAB)

  Baseline, week 4 (treatment completion) and week 8 (follow-up)

Study Arms (4)

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.

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.

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.

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.

Behavioral: Virtual Reality-based control treatment (VR-CT); Dietary Supplement: Placebo

Interventions

Virtual Reality-based cognitive remediation therapy (VR-CRT) BEHAVIORAL

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.

Group 1/4: VR high intensity + sodium butyrate; Group 2/4: VR high intensity + placebo

Virtual Reality-based control treatment (VR-CT) BEHAVIORAL

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.

Group 3/4: VR low intensity + sodium butyrate; Group 4/4: VR low intensity + placebo

HDACi butyrate DIETARY_SUPPLEMENT

Daily intake of sodium butyrate.

Group 1/4: VR high intensity + sodium butyrate; Group 3/4: VR low intensity + sodium butyrate

Placebo DIETARY_SUPPLEMENT

Daily intake of placebo.

Group 2/4: VR high intensity + placebo; Group 4/4: VR low intensity + placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• Diagnosis of schizophrenia
• Neurological disorders (including dementia)
• Dyslexia
• Severe Physical illness
• Kidney disease
• Cardiovascular disease
• Diabetes
• Alcohol or substance abuse
• Previous severe head trauma
• History of epilepsy
• Pregnancy or breastfeeding
• BMI \>30
• Bodyweight \< 45kg
• Daily use of benzodiazepines \> 22.5 mg. oxazepam or \> 7.5 mg. diazepam per day
• Serum lithium levels \> 0.8 mmol/L

Sponsors & Collaborators

• Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital: lead

Study Sites (1)

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, Denmark

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder; Cognitive Dysfunction; Mood Disorders

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Study Officials

• Kamilla Woznica Miskowiak, DMSc, DPhil

  Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

  PRINCIPAL INVESTIGATOR

• Julian Macoveanu, PhD

  Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

  STUDY DIRECTOR

Central Study Contacts

Bjørn Ole Barkholt Nordseth, Ph.D.-student

CONTACT

+4527134653; bjoern.ole.barkholt.nordseth@regionh.dk

Kamilla Woznica Miskowiak, DMSc, DPhil

CONTACT

+4522771617; kamilla.woznica.miskowiak@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 11, 2025
• First Posted: February 11, 2026
• Study Start: November 14, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)