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.
Full Title of Study: “Effect of Action-Based Cognitive Remediation on Cognition and Frontal Lobe Activity in Patients With Bipolar Disorder in Remission (PRETEC-ABC)”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: Single (Outcomes Assessor)
- Study Primary Completion Date: July 1, 2021
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.
- Behavioral: Action-Based Cognitive Remediation
- Behavioral: Unstructured support group
Arms, Groups and Cohorts
- Experimental: Action Based Cognitive Remediation
- Active Comparator: Unstructured support group
Clinical Trial Outcome Measures
- Cognitive composite score
- Time Frame: Change from baseline and week 11
- A cognitive composite based on an average of the Rey Auditory Verbal Learning Test (RAVLT), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding, verbal fluency with the letter “D”, WAIS-III Letter-Number Sequencing, Trail Making Test B (TMT B) and Rapid Visual Information Processing (RVP) from Cambridge Cognition (CANTAB).
- One Touch Stockings of Cambridge
- Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up
- A computerized neuropsychological test assessing executive functions
- Functional Assessment Short Test
- Time Frame: Baseline, week 11, and 6-months follow-up
- A semi-structured interview assessing level of functioning
Participating in This Clinical Trial
- 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.
- 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.
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: 55 Years
Are Healthy Volunteers Accepted: Accepts Healthy Volunteers
- Lead Sponsor
- Mental Health Services in the Capital Region, Denmark
- Lundbeck Foundation
- Provider of Information About this Clinical Study
- Principal Investigator: Kamilla Woznica Miskowiak, Professor – Mental Health Services in the Capital Region, Denmark
- Overall Official(s)
- Kamilla W Miskowiak, Dr, Principal Investigator, Mental Health Services, Capital Region of Denmark
- Overall Contact(s)
- Kamilla W Miskowiak, Dr, +45 35336608, firstname.lastname@example.org
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