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

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ClinicalTrials.gov Identifier: NCT03295305
Recruitment Status : Completed
First Posted : September 27, 2017
Last Update Posted : March 4, 2020
Sponsor:
Collaborator:
Lundbeck Foundation
Information provided by (Responsible Party):
Kamilla Woznica Miskowiak, Mental Health Services in the Capital Region, Denmark

Tracking Information
First Submitted Date  ICMJE September 15, 2017
First Posted Date  ICMJE September 27, 2017
Last Update Posted Date March 4, 2020
Actual Study Start Date  ICMJE January 1, 2017
Actual Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 26, 2017)
  • Rey Auditory Verbal Learning Test [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing verbal memory
  • Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing attention
  • Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Digit Span [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing executive functions
  • Verbal fluency with the letter "D" and 'S" [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing executive functions
  • WAIS-III Letter-Number Sequencing [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing executive functions
  • Trail Making Test B [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing psychomotor speed
  • Trail Making Test A [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing executive functions
  • Rapid Visual Information Processing (RVP) from Cambridge Cognition (CANTAB) [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing sustained attention
  • Spatial Working Memory (SWM) from Cambridge Cognition [ Time Frame: Baseline, two weeks of treatment, week 11, and 6-months follow-up ]
    Neuropsychological test assessing sustained attention
  • Brief University of California, San Diego Performance-Based Skills Assessment-B (UPSA-B) [ Time Frame: Baseline, week 11, and 6-months follow-up ]
    Objective assessment of level of functioning
  • Sheehan Disability Scale [ Time Frame: Baseline, week 11, and 6-months follow-up ]
    Questionnaire on level of functioning
  • The Assessment of Quality of Life [ Time Frame: Baseline, week 11, and 6-months follow-up ]
    Questionnaire on quality of life
  • World Health Organization Quality of Life (WHOQOL-BREF) [ Time Frame: Baseline, week 11, and 6-months follow-up ]
    Questionnaire on quality of life
  • Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) [ Time Frame: Baseline, two weeks of treatment, week 11,and 6-months follow-up ]
    Questionnaire on subjective cognitive complaints
  • Work and Social Adjustment Scale (WSAS) [ Time Frame: Baseline, week 11, and 6-months follow-up ]
    Questionnaire on occupational functioning
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Effect of Action-Based Cognitive Remediation in Patients With Bipolar Disorder
Official Title  ICMJE Effect of Action-Based Cognitive Remediation on Cognition and Frontal Lobe Activity in Patients With Bipolar Disorder in Remission (PRETEC-ABC)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Bipolar Disorder
  • Cognitive Impairment
Intervention  ICMJE
  • Behavioral: Action-Based Cognitive Remediation
  • Behavioral: Unstructured support group
Study Arms  ICMJE
  • Experimental: Action Based Cognitive Remediation
    Intervention: Behavioral: Action-Based Cognitive Remediation
  • Active Comparator: Unstructured support group
    Intervention: Behavioral: Unstructured support group
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 3, 2020)
64
Original Estimated Enrollment  ICMJE
 (submitted: September 26, 2017)
116
Actual Study Completion Date  ICMJE January 25, 2020
Actual Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03295305
Other Study ID Numbers  ICMJE H-16043480
2012-58-0004 ( Registry Identifier: Danish Data Protection Agency )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kamilla Woznica Miskowiak, Mental Health Services in the Capital Region, Denmark
Study Sponsor  ICMJE Mental Health Services in the Capital Region, Denmark
Collaborators  ICMJE Lundbeck Foundation
Investigators  ICMJE
Principal Investigator: Kamilla W Miskowiak, Dr Mental Health Services, Capital Region of Denmark
PRS Account Mental Health Services in the Capital Region, Denmark
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP