Clinical trial NCT03295305: Effect of Action-Based Cognitive Remediation in Patients With Bipolar Disorder
Official title: Effect of Action-Based Cognitive Remediation on Cognition and Frontal Lobe Activity in Patients With Bipolar Disorder in Remission (PRETEC-ABC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bipolar Disorder
Cognitive Impairment
Keywords: Biomarker
Bipolar Disorder
Cognition
Cognitive Impairment
cognitive remediation
functional magnetic resonance imaging
pro-cognitive effect
Lead sponsor: Mental Health Services in the Capital Region, Denmark
Sponsor class: OTHER
Collaborators: name: Lundbeck Foundation
First posted: 2017-09-27
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: PRETEC-ABC aims to assess the effect of a new form of cognitive remediation, Action-Based Cognitive Remediation (ABCR), in patients with bipolar disorder in remission on cognition, and to assess the neural assays for treatment effects with the purpose of identifying a neural biomarker for pro-cognitive effect. It is hypothesized (i) that ABCR vs. a control treatment has a beneficial effect on cognition in remitted patients with bipolar disorder remission. It is hypothesized (ii) that this treatment-associated improvement of cognition translates into better functional capacity at a six months follow-up assessment (secondary outcome). Finally, as an exploratory measure, it is hypothesized that ABCR will produce an early change in frontal activity and that this activity will correlate with ABCR-associated improvements in cognitive function.

Detailed description: The trial will include outpatients with BD in full or partial remission (a score ≤14 on the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Recruitment will be carried out through the ongoing Bipolar Illness Onset (BIO) study, the Copenhagen Affective Disorder Clinic, Psychiatric Centre Copenhagen, Rigshospitalet, other mental health centres, consultant psychiatrists in the Capital Region of Denmark, and through advertisements on relevant websites.

Participants will undergo an eligibility assessment followed by randomisation. When 4 - 6 participants have been randomised to either the ABCR or the control group, the baseline assessments are carried out. The baseline assessment is completed over two days, 1 - 3 days apart. A fMRI scan is carried out on day 1 encompassing spatial and verbal working memory N-back tasks, a picture encoding task, a resting state and a structural scan. On day 2, a blood sample is drawn in the morning, followed by administration of a comprehensive neuropsychological test battery. Participants fill in questionnaires concerning subjective cognitive complaints, psychosocial functioning and quality of life and functional capacity is assessed using a clinician-rated interview and a performance based assessment. Sleep quantity and quality in the past three days is assessed. After two weeks of ABCR or control treatment, functional MRI, neuropsychological testing an assessment of mood and subjective cognition are repeated. These assessments, as well as assessments of functional capacity and quality of life, are repeated within two weeks after treatment completion and six months after treatment completion.

Block randomisation is carried out by Pharma Consulting Group, stratified by gender and age (patients \< or ≥ 35 years).

Power calculation was also carried out by Pharma Consulting Group based on findings from a previous RCT in our group assessing the effect of 8 weeks of EPO treatment on the same cognitive composite score. In PreTEC-ABC, a clinically relevant difference between the ABCR and the control groups following 10 weeks of treatment is assumed to be 0.4 SD (corresponding to a medium effect size) on the primary outcome, with a mean change in the cognitive composite score of 0.5 SD. Assuming a 10% drop-out rate, we will recruit up to N=58 in order to achieve complete datasets for N=52 participants.

Data will be analysed using mixed models using intention-to-treat (ITT) analyses.

Functional MRI-data will be pre-processed and analysed with the FMRIB Expert Analysis Tool (FEAT) and the "randomize" algorithm implemented in FMRIB Software Library (FSL). Functional MRI data will be analysed using a Region of interest (ROI) analysis to assess differences between the ABCR and control group in neural activity in the dlPFC and the hippocampi after 2 weeks. Exploratory whole-brain analyses will be conducted to investigate any effects in other brain regions. Any differences in neural activity will be correlated with potential changes in the cognitive composite score at weeks 2 and post-treatment. If there is a significant correlation with cognition at post-treatment, multiple regression analysis will be carried out, adjusting for mood and demographic characteristics, to assess whether early change in neural activity is predictive of pro-cognitive effects.

Eligibility criteria: Inclusion Criteria:

* Fluent Danish skills and objective cognitive impairment (a total score below cutoff, or scores below cutoff 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) on the Screen for Cognitive Impairment in Psychiatry - Danish version (SCIP-D).
* Patients must meet the ICD-10 diagnosis of BD (type I and II) confirmed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview.

Exclusion Criteria:

* Daily use of benzodiazepines \> 22.5 mg oxazepam, pregnancy, current drug or substance abuse (three months prior to inclusion), previous serious head trauma, severe physical illness, neurological illness, schizophrenia or schizoaffective disorder, dyslexia, claustrophobia, having a pacemaker or other metal implants inside the body and electroconvulsive therapy in the three months prior to inclusion.

Primary outcomes:
measure: Cognitive composite score
timeFrame: Change from baseline and week 11
Secondary outcomes:
measure: One Touch Stockings of Cambridge
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Functional Assessment Short Test
timeFrame: Baseline, week 11, and 6-months follow-up
Other outcomes:
measure: Rey Auditory Verbal Learning Test
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Digit Span
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Verbal fluency with the letter "D" and 'S"
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: WAIS-III Letter-Number Sequencing
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Trail Making Test B
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Trail Making Test A
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Rapid Visual Information Processing (RVP) from Cambridge Cognition (CANTAB)
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Spatial Working Memory (SWM) from Cambridge Cognition
timeFrame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
measure: Brief University of California, San Diego Performance-Based Skills Assessment-B (UPSA-B)
timeFrame: Baseline, week 11, and 6-months follow-up
measure: Sheehan Disability Scale
timeFrame: Baseline, week 11, and 6-months follow-up
measure: The Assessment of Quality of Life
timeFrame: Baseline, week 11, and 6-months follow-up
measure: World Health Organization Quality of Life (WHOQOL-BREF)
timeFrame: Baseline, week 11, and 6-months follow-up
measure: Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA)
timeFrame: Baseline, two weeks of treatment, week 11,and 6-months follow-up
measure: Work and Social Adjustment Scale (WSAS)
timeFrame: Baseline, week 11, and 6-months follow-up
Locations:
city: Copenhagen
country: Denmark
facility: Mental Health Services, Capital Region of Denmark, Copenhagen University Hospital, Rigshospitalet
Study officials:
affiliation: Mental Health Services, Capital Region of Denmark
name: Kamilla W Miskowiak, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ott CV, Vinberg M, Kessing LV, Bowie CR, Forman JL, Miskowiak KW. Effect of Action-Based Cognitive Remediation on cognitive impairment in patients with remitted bipolar disorder: A randomized controlled trial. Bipolar Disord. 2021 Aug;23(5):487-499. doi: 10.1111/bdi.13021. Epub 2020 Oct 29.
citation: Ott CV, Vinberg M, Bowie CR, Christensen EM, Knudsen GM, Kessing LV, Miskowiak KW. Effect of action-based cognitive remediation on cognition and neural activity in bipolar disorder: study protocol for a randomized controlled trial. Trials. 2018 Sep 12;19(1):487. doi: 10.1186/s13063-018-2860-8.