Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

Effect of action-based cognitive remediation on cognition and neural activity in bipolar disorder: study protocol for a randomized controlled trial

Authors: Caroline V. Ott, Maj Vinberg, Christopher R. Bowie, Ellen Margrethe Christensen, Gitte M. Knudsen, Lars V. Kessing, Kamilla W. Miskowiak

Published in: Trials | Issue 1/2018

Login to get access

Abstract

Background

Cognitive impairment is present in bipolar disorder (BD) during the acute and remitted phases and hampers functional recovery. However, there is currently no clinically available treatment with direct and lasting effects on cognitive impairment in BD. We will examine the effect of a novel form of cognitive remediation, action-based cognitive remediation (ABCR), on cognitive impairment in patients with BD, and explore the neural substrates of potential treatment efficacy on cognition.

Methods/design

The trial has a randomized, controlled, parallel-group design. In total, 58 patients with BD in full or partial remission aged 18–55 years with objective cognitive impairment will be recruited. Participants are randomized to 10 weeks of ABCR or a control group. Assessments encompassing neuropsychological testing and mood ratings, and questionnaires on subjective cognitive complaints, psychosocial functioning, and quality of life are carried out at baseline, after 2 weeks of treatment, after the end of treatment, and at a six-month-follow-up after treatment completion. Functional magnetic resonance imaging scans are performed at baseline and 2 weeks into treatment. The primary outcome is a cognitive composite score spanning verbal memory, attention, and executive function. Two complete data sets for 52 patients will provide a power of 80% to detect a clinically relevant between-group difference on the primary outcome. Behavioral data will be analyzed using mixed models in SPSS while MRI data will be analyzed with the FMRIB Expert Analysis Tool (FEAT). Early treatment-related changes in neural activity from baseline to week 2 will be investigated for the dorsal prefrontal cortex and hippocampus as the regions of interest and with an exploratory whole-brain analysis.

Discussion

The results will provide insight into whether ABCR has beneficial effects on cognition and functioning in remitted patients with BD. The results will also provide insight into early changes in neural activity associated with improvement of cognition, which can aid future treatment development.

Trial registration

Clinicaltrials.​gov, NCT03295305. Registered on 26 September 2017.
Appendix
Available only for authorised users
Literature
1.
Cullen B, Ward J, Graham NA, Deary IJ, Pell JP, Smith DJ, et al. Prevalence and correlates of cognitive impairment in euthymic adults with bipolar disorder: a systematic review. J Affect Disord. 2016;205:165–81.CrossRef
2.
Jensen JH, Knorr U, Vinberg M, Kessing LV, Miskowiak KW. Discrete neurocognitive subgroups in fully or partially remitted bipolar disorder: associations with functional abilities. J Affect Disord. 2016;205:378–86.CrossRef
3.
Burdick KE, Russo M, Frangou S, Mahon K, Braga RJ, Shanahan M, et al. Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications. Psychol Med. 2014;44:3083.CrossRef
4.
Baune BT, Malhi GS. A review on the impact of cognitive dysfunction on social, occupational, and general functional outcomes in bipolar disorder. Bipolar Disord. 2015;17:41–55.CrossRef
5.
Tse S, Chan S, Ng KL, Yatham LN. Meta-analysis of predictors of favorable employment outcomes among individuals with bipolar disorder. Bipolar Disord. 2014;16:217–29.CrossRef
6.
Olesen J, Gustavsson A, Svensson M, Wittchen H, Jönsson B. The economic cost of brain disorders in Europe. Eur J Neurol. 2012;19:155–62.CrossRef
7.
Miskowiak KW, Carvalho AF, Vieta E, Kessing LV. Cognitive enhancement treatments for bipolar disorder: a systematic review and methodological recommendations. Eur Neuropsychopharmacol. 2016;26:1541–61.CrossRef
8.
Miskowiak K, Kjaerstad H, Støttrup M, Svendsen A, Demant K, Hoeffding L, et al. The catechol-O-methyltransferase (COMT) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder. Bipolar Disord. 2017;19:214–24.CrossRef
9.
Miskowiak KW, Burdick KE, Martinez Aran A, Bonnin CM, Bowie CR, Carvalho AF, et al. Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force. Press. 2017.
10.
Nathan PJ, Phan KL, Harmer CJ, Mehta MA, Bullmore ET. Increasing pharmacological knowledge about human neurological and psychiatric disorders through functional neuroimaging and its application in drug discovery. Curr Opin Pharmacol. 2014;14:54–61.CrossRef
11.
Miskowiak KW, Kessing LV. Cognitive enhancement in bipolar disorder: current evidence and methodological considerations. In: Carvalho A, Vieta E, editors. Treat. Bipolar Disord. - Integr. Treat. Strateg. Future Dir. Oxford: Oxford University Press; 2015.
12.
Anaya C, Martinez Aran A, Ayuso-Mateos JL, Wykes T, Vieta E, Scott J. A systematic review of cognitive remediation for schizo-affective and affective disorders. J Affect Disord. 2012;142:13–21.CrossRef
13.
Veeh J, Kopf J, Kittel-Schneider S, Deckert J, Reif A. Cognitive remediation for bipolar patients with objective cognitive impairment: a naturalistic study. Int J Bipolar Disord. 2017;5:8.CrossRef
14.
Lewandowski KE, Sperry SH, Cohen BM, Norris LA, Fitzmaurice GM, Ongur D, et al. Treatment to enhance cognition in bipolar disorder (TREC-BD): efficacy of a randomized controlled trial of cognitive remediation versus active control. J. Clin. Psychiatry. 2017;78(9):e1242–9.CrossRef
15.
Demant KM, Vinberg M, Kessing LV, Miskowiak KW. Effects of short-term cognitive remediation on cognitive dysfunction in partially or fully remitted individuals with bipolar disorder: results of a randomised controlled trial. PLoS One. 2015;10:e0127955.CrossRef
16.
Demant KM, Vinberg M, Kessing LV, Miskowiak KW. Assessment of subjective and objective cognitive function in bipolar disorder: correlations, predictors and the relation to psychosocial function. Psychiatry Res. 2015;229:565–71.CrossRef
17.
Jensen JH, Støttrup MM, Nayberg E, Knorr U, Ullum H, Purdon SE, et al. Optimising screening for cognitive dysfunction in bipolar disorder: validation and evaluation of objective and subjective tools. J Affect Disord. 2015;187:10–9.CrossRef
18.
19.
McGurk SR, Twamley EW, Sitzer DI, McHugo GJ, Mueser KT. A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry. 2007;164:1791–802.CrossRef
20.
Cremaschi L, Penzo B, Palazzo M, Dobrea C, Cristoffanini M, Dell’Osso B, et al. Assessing working memory via N-back task in euthymic bipolar I disorder patients: a review of functional magnetic resonance imaging studies. Neuropsychobiology. 2013;68:63–70.CrossRef
21.
Monks PJ, Thompson JM, Bullmore ET, Suckling J, Brammer MJ, Williams SC, et al. A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction. Bipolar Disord. 2004;6:550–64.CrossRef
22.
Ramsay IS, MacDonald AW. Brain correlates of cognitive remediation in schizophrenia: activation likelihood analysis shows preliminary evidence of neural target engagement. Schizophr Bull. 2015;41:1276–84.CrossRef
23.
Miskowiak KW, Macoveanu J, Vinberg M, Assentoft E, Randers L, Harmer CJ, et al. Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders. Acta Psychiatr Scand. 2016;134:249–59.CrossRef
24.
Miskowiak KW, Vinberg M, Glerup L, Paulson OB, Knudsen GM, Ehrenreich H, et al. Neural correlates of improved executive function following erythropoietin treatment in mood disorders. Psychol Med. 2016;46:1679–91.CrossRef
25.
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.CrossRef
26.
Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry J Ment Sci. 1978;133:429–35.CrossRef
27.
Kessing LV, Munkholm K, Faurholt-Jepsen M, Miskowiak KW, Nielsen LB, Frikke-Schmidt R, et al. The bipolar illness onset study: research protocol for the BIO cohort study. BMJ Open. 2017;7:e015462.CrossRef
28.
Purdon SE. The Screen for Cognitive Impairment in Psychiatry: Administration and Psychometric Properties. Edmonton: PNL, Inc.; 2005.
29.
Wing JK, Babor T, Brugha T, Burke J, Cooper JE, Giel R, et al. SCAN. Schedules for clinical assessment in neuropsychiatry. Arch. Gen. Psychiatry. 1990;47:589–93.
30.
Colom F, Vieta E, Martinez-Aran A, Reinares M, Goikolea JM, Benabarre A, et al. A randomized trial on the efficacy of group psychoeducation in the prophylaxis of recurrences in bipolar patients whose disease is in remission. Arch Gen Psychiatry. 2003;60:402–7.CrossRef
31.
32.
Randolph C. RBANS manual: repeatable battery for the assessment of neuropsychological status. San Antonio: The Psychological Corporation; 1998.
33.
Borkowski JG, Benton AL, Spreen O. Word fluency and brain damage. Neuropsychologia. 1967;5:135–40.CrossRef
34.
Wechsler D. Wechsler Adult Intelligence Scale-III. San Antonio: The Psychological Corporation; 1997.
35.
Army Individual Test Battery. Manual of directions and scoring. Washington, DC: War Department, Adjutant General’s Office; 1944.
36.
Rosa AR, Sánchez-Moreno J, Martínez-Aran A, Salamero M, Torrent C, Reinares M, et al. Validity and reliability of the functioning assessment short test (FAST) in bipolar disorder. Clin Pract Epidemiol Ment Health. 2007;3:5.CrossRef
37.
Patterson TL, Goldman S, McKibbin CL, Hughs T, Jeste DV. UCSD performance-based skills assessment: development of a new measure of everyday functioning for severely mentally ill adults. Schizophr Bull. 2001;27:235–45.CrossRef
38.
Vesterager L, Christensen TØ, Olsen BB, Krarup G, Forchhammer HB, Melau M, et al. Cognitive training plus a comprehensive psychosocial programme (OPUS) versus the comprehensive psychosocial programme alone for patients with first-episode schizophrenia (the NEUROCOM trial): A study protocol for a centrally randomised, observer-blinded multi-centre clinical trial. Trials [Internet]. 2011 [cited 2016 Sep 21];12. Available from: http://​trialsjournal.​biomedcentral.​com/​articles/​10.​1186/​1745-6215-12-35.
39.
Sheehan DV. The anxiety disease. New York: Charles Scribner’s Sons; 1983.
40.
Hawthorne G, Richardson J, Osborne R. The assessment of quality of life (AQoL) instrument: a psychometric measure of health-related quality of life. Qual Life Res Int J Qual Life Asp Treat Care Rehabil. 1999;8:209–24.CrossRef
41.
42.
Rosa AR, Mercadé C, Sánchez-Moreno J, Solé B, Mar Bonnin CD, Torrent C, et al. Validity and reliability of a rating scale on subjective cognitive deficits in bipolar disorder (COBRA). J Affect Disord. 2013;150:29–36.CrossRef
43.
Mundt JC, Marks IM, Shear MK, Greist JM. The work and social adjustment scale: a simple measure of impairment in functioning. Br J Psychiatry. 2002;180:461–4.CrossRef
44.
Miskowiak KW, Burdick KE, Martinez-Aran A, Bonnin CM, Bowie CR, Carvalho AF, et al. Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force. Bipolar Disord. 2017;19(8):614–26.CrossRef
45.
Chang HH, Lee IH, Gean PW, Lee S-Y, Chi MH, Yang YK, et al. Treatment response and cognitive impairment in major depression: association with C-reactive protein. Brain Behav Immun. 2012;26:90–5.CrossRef
46.
Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Yolken R. Elevated C-reactive protein and cognitive deficits in individuals with bipolar disorder. J Affect Disord. 2013;150:456–9.CrossRef
47.
Grassi-Oliveira R, Bauer ME, Pezzi JC, Teixeira AL, Brietzke E. Interleukin-6 and verbal memory in recurrent major depressive disorder. Neuro Endocrinol Lett. 2011;4:540–4.
48.
Rosenblat JD, Brietzke E, Mansur RB, Maruschak NA, Lee Y, McIntyre RS. Inflammation as a neurobiological substrate of cognitive impairment in bipolar disorder: evidence, pathophysiology and treatment implications. J Affect Disord. 2015;188:149–59.CrossRef
49.
Uyanik V, Tuglu C, Gorgulu Y, Kunduracilar H, Uyanik MS. Assessment of cytokine levels and hs-CRP in bipolar I disorder before and after treatment. Psychiatry Res. 2015;228:386–92.CrossRef
50.
Ott CV, Vinberg M, Kessing LV, Miskowiak KW. The effect of erythropoietin on cognition in affective disorders – associations with baseline deficits and change in subjective cognitive complaints. Eur Neuropsychopharmacol. 2016;26:1264–73.CrossRef
Metadata
Title
Effect of action-based cognitive remediation on cognition and neural activity in bipolar disorder: study protocol for a randomized controlled trial
Authors
Caroline V. Ott
Maj Vinberg
Christopher R. Bowie
Ellen Margrethe Christensen
Gitte M. Knudsen
Lars V. Kessing
Kamilla W. Miskowiak
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2860-8

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Study protocol

Follow-up study regarding the medium-term effectiveness of the home-visiting program “Pro Kind” at age 7 years: study protocol for a randomized controlled trial

Study protocol

The efficacy of adding group behavioral activation to usual care in patients with fibromyalgia and major depression: design and protocol for a randomized clinical trial

Methodology

Improved adherence adjustment in the Coronary Drug Project

Study protocol

Engaging family supporters of adult patients with diabetes to improve clinical and patient-centered outcomes: study protocol for a randomized controlled trial

Review

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials

Study protocol

Hypertension management for community-dwelling older people with diabetes in Nanchang, China: study protocol for a cluster randomized controlled trial