Epigenetic Enhancement of Cognitive Training in Aging Mood Disorder Populations

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

Interventions

BEHAVIORAL

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

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.

BEHAVIORAL

Virtual Reality-based control treatment (VR-CT)

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.

DIETARY_SUPPLEMENT

HDACi butyrate

Daily intake of sodium butyrate.

DIETARY_SUPPLEMENT

Placebo

Daily intake of placebo.

Sponsors & Collaborators

• Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

  lead OTHER

Principal Investigators

• Kamilla Woznica Miskowiak, DMSc, DPhil · Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

• Julian Macoveanu, PhD · Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-11-14

Primary Completion

2027-07-01

Completion

2028-07-01

Countries

• Denmark

Study Locations