Brain Imaging, Cognitive Enhancement and Early Schizophrenia
NCT ID: NCT01561859
Last Updated: 2021-02-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
NA
102 participants
INTERVENTIONAL
2012-06-30
2018-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Cognitive Enhancement Therapy for Early-Stage Schizophrenia
NCT00167362
Brain Imaging, Attention, and Auditory Processing in Schizophrenia
NCT03068806
Feasibility of Providing Cognitive Remediation to People With Schizophrenia in a Clinical Network
NCT00930150
Neuropsychiatric Evaluation of Healthy Volunteers and Adults With Schizophrenia
NCT00001323
Cognitive Remediation of Schizophrenia in a Community Mental Health Setting
NCT01988714
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The investigators have posited that CET can be particularly effective as an early intervention strategy by capitalizing on a fronto-temporal plasticity reserve, and the investigators are now observing compelling, albeit preliminary evidence that CET can indeed slow the progression of gray matter loss in these very regions of the brain, which is associated with significantly improved cognition (see Preliminary Studies). Preserved structural integrity and improved brain function in fronto-temporal regions may be the critical mechanisms for supporting cognitive improvement in early course schizophrenia, yet remarkably little is known about the neurobiologic effects of cognitive rehabilitation, the durability of these effects post-treatment, and whether an initial fronto-temporal reserve portends a greater treatment response. Our exciting preliminary findings of the neuroprotective effects of CET represent the first study to demonstrate that the structural integrity of the brain in the early course of schizophrenia can be altered using cognitive rehabilitation. It is critical that these morphologic findings are examined with more advanced imaging techniques in larger samples to gain a precise understanding of the underlying neurobiologic mechanisms and predictors of cognitive and functional enhancement in early course schizophrenia. These goals are reflective of the strategic plan of NIMH to identify underlying neural mechanisms of mental disorders that can facilitate treatment, and personalize care to optimize treatment response. To accomplish this, the investigators propose to use comprehensive structural and functional imaging methods to study 102 new early course schizophrenia patients treated for 18 months in a randomized trial of CET or Enriched Supportive Therapy (EST) and: Aim #1: Confirm the neuroprotective effects of CET on fronto-temporal brain structure. Structural magnetic resonance imaging (MRI) assessments will be collected along with cognitive and functional outcome data at baseline, 9, and 18 months. It is hypothesized that patients treated with CET will demonstrate decreased loss of fronto-temporal gray matter relative to EST, and that this neuroprotection will be a mechanism of cognitive and functional improvement. Effects on other key brain regions will also be explored; Aim #2: Examine the effects of CET on fronto-temporal brain function. Functional MRI data using established executive and social cognition paradigms will be collected at baseline, 9, and 18 months along with cognitive and functional outcome data. It is hypothesized that CET patients will demonstrate enhanced fronto-temporal brain activity during these tasks relative to EST (see Section 3C.6.2 for specific predictions), and that this enhanced brain activity will be a mechanism of cognitive and functional improvement. Changes in fronto-temporal functional connectivity and their relations with improved brain structure and cognition will also be explored; and Aim #3: Examine the durability of CET effects on fronto-temporal brain structure and function, cognition, and functional outcome at 1 year post-treatment. Identical neuroimaging, cognitive, and behavioral data will be collected as those assessed during active treatment. It is hypothesized that the differential neurobiologic benefits of CET relative to EST observed in Aims 1 and 2, and the cognitive and functional benefits of CET observed during active treatment will be sustained 1 year post-treatment.
Exploratory Aim: Explore the effects of a fronto-temporal structural and functional reserve on CET treatment response. Moderator analyses will examine whether pre-treatment fronto-temporal structural and functional brain reserves (operationalized in Section 3C.8.2) predict larger cognitive and functional gains in CET. Exploratory analyses will also examine the degree to which later (18 mo) treatment improvement is dependent upon early (9 mo) neuroprotection and increased brain function, which may reflect plasticity.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Cognitive enhancement therapy
Cognitive Enhancement Therapy (CET) consists of approximately 60 hours of computer-assisted neurocognitive training in attention, memory, and problem-solving; and 45 social-cognitive group sessions that employ in vivo learning experiences to foster the development of social wisdom and success in interpersonal interactions. CET begins with 3 months of weekly 1-hour neurocognitive training in attention, after which patients begin the weekly 1.5-hour social-cognitive groups. Neurocognitive training then proceeds concurrently with the socialcognitive groups
Cognitive Enhancement Therapy
Cognitive Enhancement Therapy (CET) consists of approximately 60 hours of computer-assisted neurocognitive training in attention, memory, and problem-solving; and 45 social-cognitive group sessions that employ in vivo learning experiences to foster the development of social wisdom and success in interpersonal interactions. CET begins with 3 months of weekly 1-hour neurocognitive training in attention, after which patients begin the weekly 1.5-hour social-cognitive groups. Neurocognitive training then proceeds concurrently with the socialcognitive groups.
Enriched Supportive Therapy
Enriched Supportive Therapy is an individual approach that includes the established principles of supportive therapy previously tested by our group, which are "enriched" by selected practice principles from the effective Personal Therapy. These manualized supportive therapeutic practices include active listening, correct empathy, appropriate reassurance, basic psychoeducation, including computer-based educational programs, reinforcement of health-promoting initiatives, the provision of case management, and reliance on the advocacy and advice of the therapist in times of crisis.
Enriched Supportive Therapy
Enriched Supportive Therapy is an individual approach that includes the established principles of supportive therapy previously tested by our group, which are "enriched" by selected practice principles from the effective Personal Therapy. These manualized supportive therapeutic practices include active listening, correct empathy, appropriate reassurance, basic psychoeducation, including computer-based educational programs, reinforcement of health-promoting initiatives, the provision of case management, and reliance on the advocacy and advice of the therapist in times of crisis.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Cognitive Enhancement Therapy
Cognitive Enhancement Therapy (CET) consists of approximately 60 hours of computer-assisted neurocognitive training in attention, memory, and problem-solving; and 45 social-cognitive group sessions that employ in vivo learning experiences to foster the development of social wisdom and success in interpersonal interactions. CET begins with 3 months of weekly 1-hour neurocognitive training in attention, after which patients begin the weekly 1.5-hour social-cognitive groups. Neurocognitive training then proceeds concurrently with the socialcognitive groups.
Enriched Supportive Therapy
Enriched Supportive Therapy is an individual approach that includes the established principles of supportive therapy previously tested by our group, which are "enriched" by selected practice principles from the effective Personal Therapy. These manualized supportive therapeutic practices include active listening, correct empathy, appropriate reassurance, basic psychoeducation, including computer-based educational programs, reinforcement of health-promoting initiatives, the provision of case management, and reliance on the advocacy and advice of the therapist in times of crisis.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. a diagnosis of schizophrenia or schizoaffective disorder verified by the SCID (in our data patients with both conditions respond similarly to CET);
2. duration since first psychotic symptom of \< 10 years;
3. stable positive symptoms based on medical record review and SCID for at least 2 months;
4. are currently maintained on and compliant with prescribed antipsychotic medication;
5. age 18-55 years;
6. significant social and cognitive disability based on the Cognitive Style and Social Cognition Eligibility Interview utilized in previous CET studies;
7. current IQ \>= 80; and
8. the ability to read (sixth grade level or higher) and speak fluent English. This is a study of early course schizophrenia, not first-episode schizophrenia. A duration of illness since first psychotic symptom of \< 10 years is adequate to define the early phase of the illness, particularly given that the average duration of untreated psychosis is a year or more. Eligibility criteria regarding IQ are justified from previous experience with CET indicating that individuals with severe mental incapacity are better served with less cognitively advanced programs.
Exclusion Criteria
1. significant neurological or medical disorders that may produce cognitive impairment (e.g., seizure disorder, traumatic brain injury);
2. persistent suicidal or homicidal behavior;
3. a recent (within the past 3 months) history of substance abuse or dependence; and
4. any MRI contraindications such as ferromagnetic objects in the body.
18 Years
55 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Pittsburgh
OTHER
Massachusetts General Hospital
OTHER
National Institute of Mental Health (NIMH)
NIH
Beth Israel Deaconess Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Matcheri S. Keshavan MD
Stanley Cobb Professor of Psychiatry
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Matcheri Keshavan, MD
Role: PRINCIPAL_INVESTIGATOR
Beth Israel Deaconess Medical Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Massachusetts Institute of Technology
Cambridge, Massachusetts, United States
Massachusetts General Hospital
Charlestown, Massachusetts, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Western Psychiatry Institute and Clinic
Pittsburgh, Pennsylvania, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Keshavan MS, Hogarty GE. Brain maturational processes and delayed onset in schizophrenia. Dev Psychopathol. 1999 Summer;11(3):525-43. doi: 10.1017/s0954579499002199.
Eack SM, Hogarty GE, Cho RY, Prasad KM, Greenwald DP, Hogarty SS, Keshavan MS. Neuroprotective effects of cognitive enhancement therapy against gray matter loss in early schizophrenia: results from a 2-year randomized controlled trial. Arch Gen Psychiatry. 2010 Jul;67(7):674-82. doi: 10.1001/archgenpsychiatry.2010.63. Epub 2010 May 3.
Insel TR. Translating scientific opportunity into public health impact: a strategic plan for research on mental illness. Arch Gen Psychiatry. 2009 Feb;66(2):128-33. doi: 10.1001/archgenpsychiatry.2008.540.
Wojtalik JA, Mesholam-Gately RI, Hogarty SS, Greenwald DP, Litschge MY, Sandoval LR, Shashidhar G, Guimond S, Keshavan MS, Eack SM. Confirmatory Efficacy of Cognitive Enhancement Therapy for Early Schizophrenia: Results From a Multisite Randomized Trial. Psychiatr Serv. 2022 May;73(5):501-509. doi: 10.1176/appi.ps.202000552. Epub 2021 Sep 2.
Hegde RR, Guimond S, Bannai D, Zeng V, Padani S, Eack SM, Keshavan MS. Theory of Mind impairments in early course schizophrenia: An fMRI study. J Psychiatr Res. 2021 Apr;136:236-243. doi: 10.1016/j.jpsychires.2021.02.010. Epub 2021 Feb 13.
Guimond S, Ling G, Drodge J, Matheson H, Wojtalik JA, Lopez B, Collin G, Brady R, Mesholam-Gately RI, Thermenos H, Eack SM, Keshavan MS. Functional connectivity associated with improvement in emotion management after cognitive enhancement therapy in early-course schizophrenia. Psychol Med. 2022 Sep;52(12):2245-2254. doi: 10.1017/S0033291720004110. Epub 2020 Nov 13.
Hegde RR, Kelly S, Lutz O, Guimond S, Karayumak SC, Mike L, Mesholam-Gately RI, Pasternak O, Kubicki M, Eack SM, Keshavan MS. Association of white matter microstructure and extracellular free-water with cognitive performance in the early course of schizophrenia. Psychiatry Res Neuroimaging. 2020 Nov 30;305:111159. doi: 10.1016/j.pscychresns.2020.111159. Epub 2020 Aug 14.
Guimond S, Padani S, Lutz O, Eack S, Thermenos H, Keshavan M. Impaired regulation of emotional distractors during working memory load in schizophrenia. J Psychiatr Res. 2018 Jun;101:14-20. doi: 10.1016/j.jpsychires.2018.02.028. Epub 2018 Mar 2.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2011P000267
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.