Cognitive Remediation in Schizophrenia: Efficacy and Role of Neuroplasticity in "Top-down" and "Bottom-up" Mechanisms

NCT06482918 | Recruiting

• 1 other identifier: Fondecyt 11231216
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Schizophrenia patients have deficits of different degrees in several cognitive domains, impacting their social functioning and quality of life. Cognitive remediation strategies are useful to treat cognitive deficits in patients with schizophrenia. There are at least two different cognitive remediation strategies: one has a "top-down" approach, and is aimed at higher-order cognitive processes, focusing on the training of executive functions. The other one has a "bottom-up" approach, aiming to first recovering the perceptual processing alterations that may affect performance in higher-order cognitive functions. This study addresses in parallel two research questions, one of clinical interest (Are both strategies effective in improving neurocognitive performance?) and another one focused on the psychological / neurobiological mechanisms of neurocognitive remediation (Which cognitive remediation strategies are related to changes in BDNF levels?). The specific objectives are: (1) Evaluate the effectiveness of two cognitive remediation strategies. (2) Study the critical moments of neuroplasticity for each cognitive remediation strategy, observing changes in BDNF levels at the end of the intervention and 12 weeks after the intervention. (3) Identify potential clinical and/or molecular predictors (BDNF levels or val66met polymorphism) of response for each cognitive remediation strategy. For these objectives, two randomized controlled trials with two arms will be carried out in parallel, one where patients will receive cognitive remediation and another consisting of a control group (with usual treatment). The control group subjects will remain on a waiting and observation list for 10 weeks, to later enter the active arm, which will also last 10 weeks. In one of the trials the active arm will consist of cognitive remediation therapy with a "bottom-up" approach (focused on perceptual training), while in the other trial the active arm will consist of cognitive remediation with a "top-down" approach (focused on executive skills training). Neurocognitive and clinical assessments will be carried out along with the measurement of BDNF levels at four evaluation times: one at baseline, one at the end of the observation period with treatment-as-usual, another at the end of cognitive remediation, and another after a 12 week follow-up period.

Conditions

Schizophrenia

Keywords

Cognitive Remediation; Cognitive Training; Cognition; Brain-Derived Neurotrophic Factor

Outcome Measures

Primary Outcomes (2)

• MCCB Global Cognition

  Global Cognition Composite T Score in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)

  After 10 weeks of cognitive remediation and at 12 week follow-up assessment

• BDNF levels in peripheral blood

  Brain-Derived Neurotrophic Factor levels in peripheral blood measured with ELISA

  After 10 weeks of cognitive remediation and at 12 weeks follow-up assessment

Study Arms (3)

Top-Down Cognitive Remediation

EXPERIMENTAL

Executive functions training

Behavioral: Cognitive Remediation

Bottom-Up Cognitive Remediation

EXPERIMENTAL

Perceptual training

Behavioral: Cognitive Remediation

Treatment-As-Usual

NO INTERVENTION

Treatment as usual

Interventions

Cognitive Remediation BEHAVIORAL

Computer-assisted top-down or bottom-up cognitive remediation using tablets

Bottom-Up Cognitive Remediation; Top-Down Cognitive Remediation

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of schizophrenia according to Diagnostic and Statistical Manual (DSM)-5
• Age between 18 and 59 years
• Clinically stable outpatients
• Current treatment with at least one antipsychotic medication

You may not qualify if:

• Significant medical or neurological comorbidity
• Substance use disorder with illegal drugs in active use
• Participation in a cognitive remediation program in the last 6 months

Sponsors & Collaborators

• University of Chile: lead

Study Sites (1)

Clinica Psiquiatrica Universitaria, Hospital Clinico de la Universidad de Chile

Santiago, RM, Chile

RECRUITING

Related Publications (18)

• Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016 Jul 2;388(10039):86-97. doi: 10.1016/S0140-6736(15)01121-6. Epub 2016 Jan 15.

  PMID: 26777917 BACKGROUND

• Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, O'Donovan M, Correll CU, Kane JM, van Os J, Insel TR. Schizophrenia. Nat Rev Dis Primers. 2015 Nov 12;1:15067. doi: 10.1038/nrdp.2015.67.

  PMID: 27189524 BACKGROUND

• Schaefer J, Giangrande E, Weinberger DR, Dickinson D. The global cognitive impairment in schizophrenia: consistent over decades and around the world. Schizophr Res. 2013 Oct;150(1):42-50. doi: 10.1016/j.schres.2013.07.009. Epub 2013 Aug 2.

  PMID: 23911259 BACKGROUND

• Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996 Mar;153(3):321-30. doi: 10.1176/ajp.153.3.321.

  PMID: 8610818 BACKGROUND

• Kuo SS, Almasy L, Gur RC, Prasad K, Roalf DR, Gur RE, Nimgaonkar VL, Pogue-Geile MF. Cognition and community functioning in schizophrenia: The nature of the relationship. J Abnorm Psychol. 2018 Feb;127(2):216-227. doi: 10.1037/abn0000326.

  PMID: 29528675 BACKGROUND

• Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA; CATIE Investigators; Neurocognitive Working Group. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007 Jun;64(6):633-47. doi: 10.1001/archpsyc.64.6.633.

  PMID: 17548746 BACKGROUND

• Hori H, Noguchi H, Hashimoto R, Nakabayashi T, Omori M, Takahashi S, Tsukue R, Anami K, Hirabayashi N, Harada S, Saitoh O, Iwase M, Kajimoto O, Takeda M, Okabe S, Kunugi H. Antipsychotic medication and cognitive function in schizophrenia. Schizophr Res. 2006 Sep;86(1-3):138-46. doi: 10.1016/j.schres.2006.05.004. Epub 2006 Jun 21.

  PMID: 16793238 BACKGROUND

• Moncrieff J, Cohen D, Mason JP. The subjective experience of taking antipsychotic medication: a content analysis of Internet data. Acta Psychiatr Scand. 2009 Aug;120(2):102-11. doi: 10.1111/j.1600-0447.2009.01356.x. Epub 2009 Feb 15.

  PMID: 19222405 BACKGROUND

• McCleery A, Nuechterlein KH. Cognitive impairment in psychotic illness: prevalence, profile of impairment, developmental course, and treatment considerations . Dialogues Clin Neurosci. 2019 Sep;21(3):239-248. doi: 10.31887/DCNS.2019.21.3/amccleery.

  PMID: 31749648 BACKGROUND

• Marder SR, Fenton W. Measurement and Treatment Research to Improve Cognition in Schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia. Schizophr Res. 2004 Dec 15;72(1):5-9. doi: 10.1016/j.schres.2004.09.010.

  PMID: 15531402 BACKGROUND

• Green MF, Nuechterlein KH. The MATRICS initiative: developing a consensus cognitive battery for clinical trials. Schizophr Res. 2004 Dec 15;72(1):1-3. doi: 10.1016/j.schres.2004.09.006. No abstract available.

  PMID: 15531401 BACKGROUND

• Best MW, Milanovic M, Iftene F, Bowie CR. A Randomized Controlled Trial of Executive Functioning Training Compared With Perceptual Training for Schizophrenia Spectrum Disorders: Effects on Neurophysiology, Neurocognition, and Functioning. Am J Psychiatry. 2019 Apr 1;176(4):297-306. doi: 10.1176/appi.ajp.2018.18070849. Epub 2019 Mar 8.

  PMID: 30845819 BACKGROUND

• McGurk SR, Twamley EW, Sitzer DI, McHugo GJ, Mueser KT. A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry. 2007 Dec;164(12):1791-802. doi: 10.1176/appi.ajp.2007.07060906.

  PMID: 18056233 BACKGROUND

• Wykes T, Huddy V, Cellard C, McGurk SR, Czobor P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry. 2011 May;168(5):472-85. doi: 10.1176/appi.ajp.2010.10060855. Epub 2011 Mar 15.

  PMID: 21406461 BACKGROUND

• Lejeune JA, Northrop A, Kurtz MM. A Meta-analysis of Cognitive Remediation for Schizophrenia: Efficacy and the Role of Participant and Treatment Factors. Schizophr Bull. 2021 Jul 8;47(4):997-1006. doi: 10.1093/schbul/sbab022.

  PMID: 33772310 BACKGROUND

• Vita A, Barlati S, Ceraso A, Nibbio G, Ariu C, Deste G, Wykes T. Effectiveness, Core Elements, and Moderators of Response of Cognitive Remediation for Schizophrenia: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Psychiatry. 2021 Aug 1;78(8):848-858. doi: 10.1001/jamapsychiatry.2021.0620.

  PMID: 33877289 BACKGROUND

• Adcock RA, Dale C, Fisher M, Aldebot S, Genevsky A, Simpson GV, Nagarajan S, Vinogradov S. When top-down meets bottom-up: auditory training enhances verbal memory in schizophrenia. Schizophr Bull. 2009 Nov;35(6):1132-41. doi: 10.1093/schbul/sbp068. Epub 2009 Sep 10.

  PMID: 19745022 BACKGROUND

• Vinogradov S. Has the Time Come for Cognitive Remediation in Schizophrenia...Again? Am J Psychiatry. 2019 Apr 1;176(4):262-264. doi: 10.1176/appi.ajp.2019.19020160. No abstract available.

  PMID: 30929502 BACKGROUND

MeSH Terms

Conditions

Schizophrenia

Interventions

Cognitive Remediation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Rodrigo R. Nieto, MD PhD

  University of Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rodrigo R. Nieto, MD PhD

CONTACT

+56229788601; rnieto@uchile.cl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: June 19, 2024
• First Posted: July 1, 2024
• Study Start: June 1, 2024
• Primary Completion: March 15, 2026
• Study Completion: March 15, 2026
• Last Updated: July 1, 2024

Record last verified: 2024-06

Locations

CL (1)