NCT01561859

Brief 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 followed-up at 1-year post-treatment.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
102

participants targeted

Target at P50-P75 for not_applicable schizophrenia

Timeline
Completed

Started Jun 2012

Longer than P75 for not_applicable schizophrenia

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 21, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 23, 2012

Completed
2 months until next milestone

Study Start

First participant enrolled

June 1, 2012

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed
Last Updated

February 26, 2021

Status Verified

February 1, 2021

Enrollment Period

6 years

First QC Date

March 21, 2012

Last Update Submit

February 25, 2021

Conditions

SchizophreniaSchizoaffective Disorder

Keywords

Early Course SchizophreniaCognitive Enhancement TherapyEnriched Supportive Therapy

Outcome Measures

Primary Outcomes (3)

  • 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.

    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.

    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.

    1 year post-treatment

Secondary Outcomes (1)

  • Explore the effects of a fronto-temporal structural and functional reserve on CET treatment response.

    18 Months

Study Arms (2)

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

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.

Behavioral: Enriched Supportive Therapy

Interventions

Cognitive Enhancement TherapyBEHAVIORAL

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
Enriched Supportive TherapyBEHAVIORAL

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

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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;
  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Massachusetts Institute of Technology

Cambridge, Massachusetts, 02139, United States

Location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Western Psychiatry Institute and Clinic

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (8)

  • Keshavan MS, Hogarty GE. Brain maturational processes and delayed onset in schizophrenia. Dev Psychopathol. 1999 Summer;11(3):525-43. doi: 10.1017/s0954579499002199.

    PMID: 10532623BACKGROUND

  • 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.

    PMID: 20439824BACKGROUND

  • 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.

    PMID: 19188534BACKGROUND

  • 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.

    PMID: 34470506DERIVED

  • 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.

    PMID: 33621908DERIVED

  • 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.

    PMID: 33183362DERIVED

  • 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.

    PMID: 32919288DERIVED

  • 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.

    PMID: 29524918DERIVED

MeSH Terms

Conditions

SchizophreniaPsychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Study Officials

  • Matcheri Keshavan, MD

    Beth Israel Deaconess Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Stanley Cobb Professor of Psychiatry

Study Record Dates

First Submitted

March 21, 2012

First Posted

March 23, 2012

Study Start

June 1, 2012

Primary Completion

June 1, 2018

Study Completion

June 1, 2018

Last Updated

February 26, 2021

Record last verified: 2021-02

Locations

US(5)