Effect of Action-Based Cognitive Remediation in Patients With Bipolar Disorder (PRETEC-ABC)

Effect of Action-Based Cognitive Remediation on Cognition and Frontal Lobe Activity in Patients With Bipolar Disorder in Remission (PRETEC-ABC)

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Bipolar Disorder
• Intervention / Treatment: Behavioral: Action-Based Cognitive Remediation; Behavioral: Unstructured support group

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Mental Health Services, Capital Region of Denmark, Copenhagen University Hospital, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Action Based Cognitive Remediation	Behavioral: Action-Based Cognitive Remediation
Active Comparator: Unstructured support group	Behavioral: Unstructured support group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive composite score	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).	Change from baseline and week 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One Touch Stockings of Cambridge	A computerized neuropsychological test assessing executive functions	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Functional Assessment Short Test	A semi-structured interview assessing level of functioning	Baseline, week 11, and 6-months follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rey Auditory Verbal Learning Test	Neuropsychological test assessing verbal memory	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding	Neuropsychological test assessing attention	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Digit Span	Neuropsychological test assessing executive functions	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Verbal fluency with the letter "D" and 'S"	Neuropsychological test assessing executive functions	Baseline, two weeks of treatment, week 11, and 6-months follow-up
WAIS-III Letter-Number Sequencing	Neuropsychological test assessing executive functions	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Trail Making Test B	Neuropsychological test assessing psychomotor speed	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Trail Making Test A	Neuropsychological test assessing executive functions	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Rapid Visual Information Processing (RVP) from Cambridge Cognition (CANTAB)	Neuropsychological test assessing sustained attention	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Spatial Working Memory (SWM) from Cambridge Cognition	Neuropsychological test assessing sustained attention	Baseline, two weeks of treatment, week 11, and 6-months follow-up
Brief University of California, San Diego Performance-Based Skills Assessment-B (UPSA-B)	Objective assessment of level of functioning	Baseline, week 11, and 6-months follow-up
Sheehan Disability Scale	Questionnaire on level of functioning	Baseline, week 11, and 6-months follow-up
The Assessment of Quality of Life	Questionnaire on quality of life	Baseline, week 11, and 6-months follow-up
World Health Organization Quality of Life (WHOQOL-BREF)	Questionnaire on quality of life	Baseline, week 11, and 6-months follow-up
Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA)	Questionnaire on subjective cognitive complaints	Baseline, two weeks of treatment, week 11,and 6-months follow-up
Work and Social Adjustment Scale (WSAS)	Questionnaire on occupational functioning	Baseline, week 11, and 6-months follow-up

Collaborators and Investigators

• Sponsor: Mental Health Services in the Capital Region, Denmark
• Collaborators: Lundbeck Foundation
• Investigators: Principal Investigator: Kamilla W Miskowiak, Dr, Mental health services, Capital Region of Denmark

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: Trials. 2019 Apr 8;20(1):201.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): January 25, 2020

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 26, 2017
• First Posted (Actual): September 27, 2017

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Biomarker; functional magnetic resonance imaging; Bipolar Disorder; Cognitive Impairment; Cognition; cognitive remediation; pro-cognitive effect
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Bipolar and Related Disorders; Disease; Cognitive Dysfunction; Bipolar Disorder
• Other Study ID Numbers: H-16043480; 2012-58-0004 (Danish Data Protection Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No