SchizophreniaBICEPSNCT01561859
Brain Imaging, Cognitive Enhancement and Early Schizophrenia
A study testing Cognitive Enhancement Therapy and Enriched Supportive Therapy in people with Schizophrenia and Schizoaffective Disorder, run by Beth Israel Deaconess Medical Center at 5 sites in United States.
Trial summary
The proposed project is designed to examine the effects of cognitive rehabilitation on brain structure and function in a randomized trial of 102 early course schizophrenia patients treated for 18 months with either cognitive enhancement therapy (CET) or an Enriched Supportive Therapy (EST) control, and then… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Cognitive Enhancement Therapy and Enriched Supportive Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2012to Jun 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients will be included if they have:
- a diagnosis of schizophrenia or schizoaffective disorder verified by the SCID (in our data patients with both conditions respond similarly to CET);
- duration since first psychotic symptom of < 10 years;
- stable positive symptoms based on medical record review and SCID for at least 2 months;
- are currently maintained on and compliant with prescribed antipsychotic medication;
- age 18-55 years;
Show all 9Show fewer
- significant social and cognitive disability based on the Cognitive Style and Social Cognition Eligibility Interview utilized in previous CET studies;
- current IQ >= 80; and
- 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.
Who cannot join
- In order to avoid confounders likely to affect cognition and limit response to cognitive rehabilitation, we will exclude those with:
- significant neurological or medical disorders that may produce cognitive impairment (e.g., seizure disorder, traumatic brain injury);
- persistent suicidal or homicidal behavior;
- a recent (within the past 3 months) history of substance abuse or dependence; and
- any MRI contraindications such as ferromagnetic objects in the body.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Massachusetts Institute of Technology
Cambridge, Massachusetts, 02139
Massachusetts General Hospital
Charlestown, Massachusetts, 02129
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Western Psychiatry Institute and Clinic
Pittsburgh, Pennsylvania, 15213
About this study
The proposed project is designed to examine the effects of cognitive rehabilitation on brain structure and function in a randomized trial of 102 early course schizophrenia patients treated for 18 months with either cognitive enhancement therapy (CET) or an Enriched Supportive Therapy (EST) control, and then followed-up at 1-year post-treatment.
Read the detailed description
Schizophrenia is a chronic and highly disabling disorder, making it imperative to apply interventions that alter its deleterious effects as early as possible. Impairments in neurocognition and social cognition, which appear to be linked to impaired structural and functional integrity in key brain regions, are the strongest predictors of functional disability in early course schizophrenia,making them key targets for early intervention. Although pharmacologic treatment of cognitive impairments is currently limited,our studies and others, including meta-analyses have shown that cognitive rehabilitation can be effective for addressing cognitive impairment in chronic patients. Most notably, Cognitive Enhancement Therapy (CET), a unique integrated approach to the rehabilitation of social and non-social cognitive impairments developed and tested by Hogarty and colleagues in our group, has shown substantial and lasting effects in chronic schizophrenia patients. Recently, the investigators have shown that the beneficial effects of CET can be successfully extended to those in the early phase of the disorder, resulting in large functional improvements.
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
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Cognitive Enhancement Therapy, Enriched Supportive Therapy
- Keywords
- Early Course Schizophrenia, Cognitive Enhancement Therapy, Enriched Supportive Therapy
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Enhancement TherapyBehavioural
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 TherapyBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive enhancement therapy | Experimental | 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 Receives: Behavioral: Cognitive Enhancement Therapy |
| Enriched Supportive Therapy | Active comparator | 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. Receives: Behavioral: Enriched Supportive Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirm the neuroprotective effects of CET on frontal and temporal brain structure
Aim #1: Confirm the neuroprotective effects of CET on frontal and 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 frontal and temporal gray matter relative to EST, and that this neuroprotection will be a mechanism of cognitive and functional improvement.
Measured: 18 months
Examine the effects of CET on fronto-temporal brain function.
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.
Measured: 18 Months
Examine the durability of CET effects on fronto-temporal brain structure and function, cognition, and functional outcome at 1 year post-treatment
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.
Measured: 1 year post-treatment
Secondary outcomes (1)
Explore the effects of a fronto-temporal structural and functional reserve on CET treatment response.
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.
Measured: 18 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2012 (estimated)
- Study startJun 2012
- Primary completionJun 2018
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh, Massachusetts General Hospital, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Matcheri S. Keshavan MD, Beth Israel Deaconess Medical Center
- Investigators
- Matcheri Keshavan, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01561859
- Sponsor's protocol ID
- 2011P000267
- Other IDs
- R01MH092440
- Acronym
- BICEPS
- Status last verified
- Feb 2021
- First submitted
- 21 Mar 2012
- Last updated
- 26 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Keshavan MS, Hogarty GE. Brain maturational processes and delayed onset in schizophrenia. Dev Psychopathol. 1999 Summer;11(3):525-43. doi: 10.1017/s0954579499002199.
PubMed 10532623Eack 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.
PubMed 20439824Insel 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.
PubMed 19188534Murphy SM, Flores AT, Sarpal DK, Keshavan MS, Eack SM. Quality of life in schizophrenia: Symptomatic markers of improvement over time. Psychiatr Rehabil J. 2026 Sep;49(3):247-252. doi: 10.1037/prj0000690. Epub 2026 May 18.
PubMed 42149541Wojtalik 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.
PubMed 34470506Hegde 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.
PubMed 33621908Guimond 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.
PubMed 33183362Hegde 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.
PubMed 32919288Guimond 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.
PubMed 29524918
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Imaging, Cognitive Enhancement and Early Schizophrenia
- ClinicalTrials.gov ID
- NCT01561859
- Acronym / sponsor ID
- BICEPS / 2011P000267
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- Early Course Schizophrenia, Cognitive Enhancement Therapy, Enriched Supportive Therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- University of Pittsburgh, Massachusetts General Hospital, National Institute of Mental Health (NIMH)
- Study start
- Jun 2012
- Primary completion
- Jun 2018 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 23 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed project is designed to examine the effects of cognitive rehabilitation on brain structure and function in a randomized trial of 102 early course schizophrenia patients treated for 18 months with either cognitive enhancement therapy (CET) or an Enriched Supportive Therapy (EST) control, and then followed-up at 1-year post-treatment.
Detailed description
Schizophrenia is a chronic and highly disabling disorder, making it imperative to apply interventions that alter its deleterious effects as early as possible. Impairments in neurocognition and social cognition, which appear to be linked to impaired structural and functional integrity in key brain regions, are the strongest predictors of functional disability in early course schizophrenia,making them key targets for early intervention. Although pharmacologic treatment of cognitive impairments is currently limited,our studies and others, including meta-analyses have shown that cognitive rehabilitation can be effective for addressing cognitive impairment in chronic patients. Most notably, Cognitive Enhancement Therapy (CET), a unique integrated approach to the rehabilitation of social and non-social cognitive impairments developed and tested by Hogarty and colleagues in our group, has shown substantial and lasting effects in chronic schizophrenia patients. Recently, the investigators have shown that the beneficial effects of CET can be successfully extended to those in the early phase of the disorder, resulting in large functional improvements.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cognitive enhancement therapy | Experimental | Behavioral: Cognitive Enhancement TherapyCognitive 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 | Active comparator | Behavioral: Enriched Supportive TherapyEnriched 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- a diagnosis of schizophrenia or schizoaffective disorder verified by the SCID (in our data patients with both conditions respond similarly to CET);
- duration since first psychotic symptom of < 10 years;
- stable positive symptoms based on medical record review and SCID for at least 2 months;
- are currently maintained on and compliant with prescribed antipsychotic medication;
- age 18-55 years;
Key exclusion criteria (5 listed)
- In order to avoid confounders likely to affect cognition and limit response to cognitive rehabilitation, we will exclude those with:
- significant neurological or medical disorders that may produce cognitive impairment (e.g., seizure disorder, traumatic brain injury);
- persistent suicidal or homicidal behavior;
- a recent (within the past 3 months) history of substance abuse or dependence; and
- any MRI contraindications such as ferromagnetic objects in the body.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Enhancement TherapyCognitive 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. | Behavioural | Cognitive enhancement therapy |
| Enriched Supportive TherapyEnriched 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. | Behavioural | Enriched Supportive Therapy |
Primary outcome
Confirm the neuroprotective effects of CET on frontal and temporal brain structure
Time frame: 18 months
Aim #1: Confirm the neuroprotective effects of CET on frontal and 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 frontal and temporal gray matter relative to EST, and that this neuroprotection will be a mechanism of cognitive and functional improvement.
Examine the effects of CET on fronto-temporal brain function.
Time frame: 18 Months
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.
Examine the durability of CET effects on fronto-temporal brain structure and function, cognition, and functional outcome at 1 year post-treatment
Time frame: 1 year post-treatment
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.
1 secondary outcome
Explore the effects of a fronto-temporal structural and functional reserve on CET treatment response.
Time frame: 18 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2021.
- Background: PubMed 10532623Keshavan MS, Hogarty GE. Brain maturational processes and delayed onset in schizophrenia. Dev Psychopathol. 1999 Summer;11(3):525-43. doi: 10.1017/s0954579499002199.
- Background: PubMed 20439824Eack 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.
- Background: PubMed 19188534Insel 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.
- Derived from this study: PubMed 42149541Murphy SM, Flores AT, Sarpal DK, Keshavan MS, Eack SM. Quality of life in schizophrenia: Symptomatic markers of improvement over time. Psychiatr Rehabil J. 2026 Sep;49(3):247-252. doi: 10.1037/prj0000690. Epub 2026 May 18.
- Derived from this study: PubMed 34470506Wojtalik 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.
- Derived from this study: PubMed 33621908Hegde 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.
- Derived from this study: PubMed 33183362Guimond 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.
- Derived from this study: PubMed 32919288Hegde 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.
- Derived from this study: PubMed 29524918Guimond 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matcheri Keshavan, MD principal investigator
Beth Israel Deaconess Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Enhancement Therapy and Enriched Supportive Therapy in people with Schizophrenia and Schizoaffective Disorder, run by Beth Israel Deaconess Medical Center at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirm the neuroprotective effects of CET on frontal and temporal brain structure (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01561859, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2021.