<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01683539</url>
  </required_header>
  <id_info>
    <org_study_id>2837E</org_study_id>
    <secondary_id>2R01MH077210-05A1</secondary_id>
    <nct_id>NCT01683539</nct_id>
  </id_info>
  <brief_title>Understanding How Cognitive Remediation Works</brief_title>
  <acronym>Cog-2</acronym>
  <official_title>A Dismantling Study of Cognitive Remediation for Supported Employment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston University Charles River Campus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston University Charles River Campus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is aimed at evaluating whether the computer-based cognitive exercises in the&#xD;
      Thinking Skills for Work (TSW) program are critical to improving work and cognitive outcomes&#xD;
      in consumers with serious mental illness and cognitive impairment enrolled in supported&#xD;
      employment (SE), or whether a streamlined version of TSW without this component (the&#xD;
      Cognitive Skills for Work (CSW) program) is equally effective for some or all consumers. An&#xD;
      RCT will be conducted at two sites (Mental Health Center of Greater Manchester in New&#xD;
      Hampshire and Thresholds Inc. in Illinois) with 244 consumers randomly assigned to one of two&#xD;
      groups (122 each, with approximately 122 participants having schizophrenia or schizoaffective&#xD;
      disorder and 122 of the participants having other diagnoses): 1) TSW, or 2) CSW. The TSW and&#xD;
      CSW programs will be delivered by the same Cognitive Specialists, who will work as members of&#xD;
      the SE team to integrate cognitive and vocational services. All participants will continue to&#xD;
      receive SE services. Participants will be assessed at baseline, post-treatment at 8 months&#xD;
      (after completion of the active teaching components of TSW or CSW), and at 16 and 24 months&#xD;
      post-baseline to evaluate cognitive functioning, symptoms, and quality of life. All work&#xD;
      outcomes will be tracked weekly.&#xD;
&#xD;
      In addition, a supplementary study, commencing in September 2015, will assess a promising&#xD;
      biomarker for understanding the mechanisms underlying the effects of cognitive remediation,&#xD;
      brain-derived neurotrophic factor (BDNF), in new enrollees in the parent R01 study. This&#xD;
      supplement will complement the aims of the parent R01 by shedding light on possible&#xD;
      mechanisms related to how TSW works and for whom, thereby informing efforts to refine and&#xD;
      improve the program, as well as targeting individuals who fail to benefit. The supplement&#xD;
      will take place at the same sites as the parent R01.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Unemployment is a major burden for people with severe mental illness (SMI) such as&#xD;
      schizophrenia, with competitive work rates typically between 10-20%. Over the past two&#xD;
      decades, supported employment (SE) has been shown to improve competitive work in persons with&#xD;
      SMI, and it is now considered an evidence-based practice (EBP). However, there is a need to&#xD;
      improve the effectiveness of SE, as 30-60% of consumers work little or not at all, and jobs&#xD;
      are often brief and end unsuccessfully. Cognitive remediation, when combined with vocational&#xD;
      rehabilitation, has shown promise for improving work outcomes, including in consumers in SE.&#xD;
      The most extensively studied approach is the Thinking Skills for Work (TSW) program,&#xD;
      developed by this research group, which incorporates computer-based cognitive exercises to&#xD;
      restore cognitive skills and teaching compensatory strategies by a Cognitive Specialist who&#xD;
      is integrated into the vocational rehabilitation team. Five randomized controlled trials&#xD;
      (RCTs), two conducted in SE programs (including one previously conducted by this research&#xD;
      group), have shown that adding the TSW program to vocational (SE) services improves work and&#xD;
      cognitive outcomes compared to vocational (SE) services alone.&#xD;
&#xD;
      The proposed study takes the next bold step of &quot;dismantling&quot; the TSW program to evaluate&#xD;
      whether the cognitive practice exercises component is critical to improving outcomes in SE,&#xD;
      or whether a more streamlined and efficient version of the program that focuses only on&#xD;
      teaching compensatory skills is sufficient. The study will also yield important information&#xD;
      about whether some consumers benefit from computer cognitive exercises, but not others,&#xD;
      permitting the TSW program to be individually tailored to consumers' personal needs.&#xD;
&#xD;
      In preparation for the proposed study we developed, standardized, and pilot tested a variant&#xD;
      of the TSW program, the Cognitive Skills for Work (CSW) program, that teaches compensatory&#xD;
      skills for managing cognitive difficulties but omits computer cognitive exercises, resulting&#xD;
      in a program that is approximately one-half the intensity of the original TSW program. A&#xD;
      small ongoing pilot study indicated that consumers in SE could be readily engaged and&#xD;
      retained in the CSW program and obtain work, supporting the feasibility of this streamlined&#xD;
      version of TSW. The proposed research will be an RCT conducted at two high fidelity SE&#xD;
      programs, comparing the effects of the TSW and CSW programs in consumers enrolled in SE.&#xD;
&#xD;
      The following hypotheses will be tested:&#xD;
&#xD;
      Primary Hypothesis: Participants in TSW will have better competitive work outcomes than those&#xD;
      in the CSW program. This hypothesis is based on the fact that virtually all cognitive&#xD;
      remediation research on SMI has included cognitive exercises designed to restore cognitive&#xD;
      skills, such as the computer-based cognitive exercises in TSW, with some programs also&#xD;
      teaching compensatory strategies. If the null hypothesis is not rejected, and TSW is found to&#xD;
      be not significantly more effective than CSW, then dissemination efforts can focus on the&#xD;
      more efficient CSW.&#xD;
&#xD;
      Secondary Hypothesis: Participants in TSW will improve more in cognitive functioning than&#xD;
      those in CSW. This hypothesis is based on the same rationale as Hypothesis #1.&#xD;
&#xD;
      Exploratory Analyses: In addition to evaluating whether the TSW and CSW programs differ&#xD;
      overall in their impact on vocational and cognitive outcomes, we will explore whether&#xD;
      consumer characteristics can be identified that predict a differential response to either&#xD;
      program. For example, it is possible that consumers with more severe cognitive impairment&#xD;
      will respond better to the full TSW program, whereas those with less severe impairment may&#xD;
      benefit equally well from the more efficient CSW program.&#xD;
&#xD;
      The proposed research has high potential impact for improving the outcomes of SE, an&#xD;
      established EBP for increasing competitive work in SMI, but whose effectiveness is limited by&#xD;
      the extent of consumers' cognitive impairment. Maximizing the efficiency of the TSW program,&#xD;
      a cognitive remediation program shown to improve work outcomes in two RCTs of SE programs, by&#xD;
      determining whether a more streamlined version of the program that requires about one-half&#xD;
      the time to implement (the CSW program) is equally effective, could reduce the costs of&#xD;
      disseminating and implementing the program, making it accessible to more consumers. This&#xD;
      study could also help identify which consumers benefit most from the cognitive exercises&#xD;
      component of TSW, thereby facilitating tailoring of the program to the individual's personal&#xD;
      needs. Ultimately, this research could play a critical role in making the dream of&#xD;
      competitive work a reality for many consumers with SMI.&#xD;
&#xD;
      In addition, a supplementary study, commencing in September 2015, will assess a promising&#xD;
      biomarker for understanding the mechanisms underlying the effects of cognitive remediation,&#xD;
      brain-derived neurotrophic factor (BDNF), in new enrollees in the parent R01 study. BDNF is a&#xD;
      widely distributed protein throughout the central nervous system that promotes neuronal&#xD;
      growth and is associated with a broad range of cognitive functions. Limited research suggests&#xD;
      that cognitive remediation increases serum BDNF levels, including one study of schizophrenia&#xD;
      and another study of Parkinson's disease. This supplemental study will provide a test of&#xD;
      whether computerized cognitive training contributes to increased BDNF levels, and whether&#xD;
      increases in BDNF are associated with improved cognitive functioning. The supplement will&#xD;
      take advantage of the ongoing parent R01 study of the TSW program by measuring BDNF levels at&#xD;
      baseline, following delivery of computerized cognitive training/teaching coping skills (6-8&#xD;
      months after baseline), and at two follow-ups (16 and 24 months after baseline) in a&#xD;
      diagnostically heterogeneous sample of 38 consumers with impaired cognitive functioning. This&#xD;
      supplement will complement the aims of the parent R01 by shedding light on possible&#xD;
      mechanisms related to how TSW works and for whom, thereby informing efforts to refine and&#xD;
      improve the program, as well as targeting individuals who fail to benefit.&#xD;
&#xD;
      The supplementary study will test the following hypotheses:&#xD;
&#xD;
      Primary Hypothesis: Participants in TSW will show greater increases in BDNF levels from&#xD;
      baseline to post-training than participants in CSW. This hypothesis is based on the&#xD;
      expectation that the computerized cognitive training exercises in TSW will lead to greater&#xD;
      improvements in cognitive functioning than training in compensatory strategies only in CSW,&#xD;
      with increases in BDNF levels associated with improved cognitive performance. We also expect&#xD;
      that greater increases in BDNF for the TSW group will be maintained at the 16- and 24 month&#xD;
      follow-up assessments.&#xD;
&#xD;
      Secondary Hypotheses: 1.) Greater improvements in cognitive functioning from baseline to the&#xD;
      post-training and follow-up assessments in TSW than CSW will be associated with stronger&#xD;
      increases in BDNF levels over the same assessment points. This hypothesis tests whether&#xD;
      greater gains in BDNF levels for TSW mediate the long-term and sustained improvements in&#xD;
      cognitive functioning for this program compare to CSW. 2.) Lower baseline BDNF levels will be&#xD;
      associated with less gain in cognitive functioning for TSW. This hypothesis tests whether&#xD;
      baseline BDNF levels moderate the effectiveness of TSW on improving cognitive functioning,&#xD;
      with lower BDNF levels predicting less benefit. BDNF could both be found to be both a&#xD;
      mediator and a moderator of the effects of cognitive remediation on improving cognitive&#xD;
      functioning.&#xD;
&#xD;
      The supplement will take place at the same sites as the parent R01: Thresholds Inc. in&#xD;
      Chicago, and the Mental Health Center of Greater Manchester, NH. Inclusion and exclusion&#xD;
      criteria for the supplemental sub-study are identical to those for parent R01 study. As&#xD;
      before, pregnancy is not a rule out for participation in the BDNF supplement study.&#xD;
      Phlebotomists associated with each site will draw one tablespoon of blood from clients at&#xD;
      each assessment timepoint, therefore, a total of up to four (4) tablespoons of blood might be&#xD;
      drawn from each client over the course of the study. Drawing BDNF specimens over the full&#xD;
      24-month course of the study will permit researchers to address several important questions&#xD;
      regarding the role of BDNF in contributing to neurocognitive functioning, both in response to&#xD;
      cognitive remediation as well as how it interacts with cognitive challenging environmental&#xD;
      demands-work.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">March 11, 2019</completion_date>
  <primary_completion_date type="Actual">March 11, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AMOUNT OF EMPLOYMENT</measure>
    <time_frame>24 MONTHS</time_frame>
    <description>TOTAL HOURS OF EMPLOYMENT FROM BASELINE TO 24 MONTHS. TOTAL WEEKS OF EMPLOYMENT FROM BASELINE TO 24 MONTHS. TOTAL NUMBER OF JOBS HELD FROM BASELINE TO 24 MONTHS.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>EXECUTIVE FUNCTIONING AND MEMORY</measure>
    <time_frame>BASELINE, 8, 16, and 24 months.</time_frame>
    <description>CHANGE FROM BASELINE IN EXECUTIVE FUNCTIONING AND MEMORY AT 8 MONTHS USING THE MATRICS COGNITIVE ASSESSMENT BATTERY.&#xD;
CHANGE FROM BASELINE IN EXECUTIVE FUNCTIONING AND MEMORY AT 16 MONTHS USING THE MATRICS COGNITIVE ASSESSMENT BATTERY.&#xD;
CHANGE FROM BASELINE IN EXECUTIVE FUNCTIONING AND MEMORY AT 24 MONTHS USING THE MATRICS COGNITIVE ASSESSMENT BATTERY.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) - AS PART OF SUPPLEMENTAL SUB-STUDY</measure>
    <time_frame>BASELINE, 8, 16, and 24 months.</time_frame>
    <description>CHANGE FROM BASELINE IN LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AT 8 MONTHS USING ABCAM'S BDNF HUMAN ELISA (ENZYME-LINKED IMMUNOSORBENT ASSAY) KIT.&#xD;
CHANGE FROM BASELINE IN LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AT 16 MONTHS USING ABCAM'S BDNF HUMAN ELISA (ENZYME-LINKED IMMUNOSORBENT ASSAY) KIT.&#xD;
CHANGE FROM BASELINE IN LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AT 24 MONTHS USING ABCAM'S BDNF HUMAN ELISA (ENZYME-LINKED IMMUNOSORBENT ASSAY) KIT.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">203</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Schizoaffective Disorder</condition>
  <condition>Chronic Mental Disorder</condition>
  <condition>Major Depression</condition>
  <condition>Bipolar Disorder</condition>
  <arm_group>
    <arm_group_label>The Thinking Skills for Work Program</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The Thinking Skills for Work Program includes 5 components delivered by a Cognitive Specialist who works collaboratively with the consumer's Employment Specialist: a) assessing the consumer's strengths and weaknesses in cognitive functioning, and analysis of the contribution of cognitive impairments and other factors to job losses and difficulties obtaining a job; b) teaching coping strategies for dealing with cognitive challenges associated with job search or maintaining a job; c) computer cognitive training involving cognitive exercises with a commercially available software program, which is designed to improve the broad range of cognitive skills through a combination of practice and strategy coaching by the Cognitive Specialist; d) job search planning; and e) job support consultation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>The Cognitive Skills for Work Program</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The Cognitive Skills for Work Program includes 4 components delivered by a Cognitive Specialist who works with the consumer's Employment Specialist: a) assessing the consumer's cognitive strengths and weaknesses their relation to job history b) teaching coping strategies for cognitive challenges associated with job search or maintenance c)job search planning, in which the consumer and the Cognitive and Employment Specialists help identify job leads based on the consumer's interests, and identify cognitive coping strategies and supports the consumer may need to succeed at the workplace; and d) job support consultation, in which the Cognitive and Employment Specialists consult with the consumer on additional cognitive coping strategies to enable the consumer to meet the demands of the job.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>The Thinking Skills for Work Program</intervention_name>
    <description>The Thinking Skills for Work includes assessment of cognitive strengths and weaknesses and their relationship with work history, computerized cognitive practice, compensatory strategy training, and integration of cognitive and work services.</description>
    <arm_group_label>The Thinking Skills for Work Program</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>The Cognitive Skills for Work Program</intervention_name>
    <description>The Cognitive Skills for Work includes assessment of cognitive strengths and weaknesses and their relationship with work history, compensatory strategy training, and integration of cognitive and work services.</description>
    <arm_group_label>The Cognitive Skills for Work Program</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic mental disorder&#xD;
&#xD;
          -  Minimum age 18.&#xD;
&#xD;
          -  Unemployed&#xD;
&#xD;
          -  Wants employment&#xD;
&#xD;
          -  Must be a recipient of services at one of two participating agencies&#xD;
&#xD;
          -  Fluent in English.&#xD;
&#xD;
          -  Cognitively impaired, as defined by 1.0 SD below normative scores in memory or&#xD;
             executive functioning&#xD;
&#xD;
          -  Willing and legally able to provide informed consent to participate in study. Subjects&#xD;
             with court appointed legal guardians will be included.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -History of neurological conditions that impair cognition&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susan McGurk, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center for Psychiatric Rehabilitation, Boston University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Thresholds</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Mental Health Center of Greater Manchester</name>
      <address>
        <city>Manchester</city>
        <state>New Hampshire</state>
        <zip>03103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2012</study_first_posted>
  <last_update_submitted>March 12, 2019</last_update_submitted>
  <last_update_submitted_qc>March 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Boston University</investigator_affiliation>
    <investigator_full_name>Susan Mcgurk</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Chronic Mental Disorder</keyword>
  <keyword>Employment</keyword>
  <keyword>Cognitive remediation</keyword>
  <keyword>Vocational rehabilitation</keyword>
  <keyword>Brain-derived Neurotrophic Factor (BDNF)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Bipolar Disorder</mesh_term>
    <mesh_term>Mental Disorders</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01683539
org study id: 2837E
secondary id: 2R01MH077210-05A1
nct id: NCT01683539
lead sponsor: 
collaborator: 
has dmc: Yes
This study is aimed at evaluating whether the computer-based cognitive exercises in the
      Thinking Skills for Work (TSW) program are critical to improving work and cognitive outcomes
      in consumers with serious mental illness and cognitive impairment enrolled in supported
      employment (SE), or whether a streamlined version of TSW without this component (the
      Cognitive Skills for Work (CSW) program) is equally effective for some or all consumers. An
      RCT will be conducted at two sites (Mental Health Center of Greater Manchester in New
      Hampshire and Thresholds Inc. in Illinois) with 244 consumers randomly assigned to one of two
      groups (122 each, with approximately 122 participants having schizophrenia or schizoaffective
      disorder and 122 of the participants having other diagnoses): 1) TSW, or 2) CSW. The TSW and
      CSW programs will be delivered by the same Cognitive Specialists, who will work as members of
      the SE team to integrate cognitive and vocational services. All participants will continue to
      receive SE services. Participants will be assessed at baseline, post-treatment at 8 months
      (after completion of the active teaching components of TSW or CSW), and at 16 and 24 months
      post-baseline to evaluate cognitive functioning, symptoms, and quality of life. All work
      outcomes will be tracked weekly.

      In addition, a supplementary study, commencing in September 2015, will assess a promising
      biomarker for understanding the mechanisms underlying the effects of cognitive remediation,
      brain-derived neurotrophic factor (BDNF), in new enrollees in the parent R01 study. This
      supplement will complement the aims of the parent R01 by shedding light on possible
      mechanisms related to how TSW works and for whom, thereby informing efforts to refine and
      improve the program, as well as targeting individuals who fail to benefit. The supplement
      will take place at the same sites as the parent R01.
Unemployment is a major burden for people with severe mental illness (SMI) such as
      schizophrenia, with competitive work rates typically between 10-20%. Over the past two
      decades, supported employment (SE) has been shown to improve competitive work in persons with
      SMI, and it is now considered an evidence-based practice (EBP). However, there is a need to
      improve the effectiveness of SE, as 30-60% of consumers work little or not at all, and jobs
      are often brief and end unsuccessfully. Cognitive remediation, when combined with vocational
      rehabilitation, has shown promise for improving work outcomes, including in consumers in SE.
      The most extensively studied approach is the Thinking Skills for Work (TSW) program,
      developed by this research group, which incorporates computer-based cognitive exercises to
      restore cognitive skills and teaching compensatory strategies by a Cognitive Specialist who
      is integrated into the vocational rehabilitation team. Five randomized controlled trials
      (RCTs), two conducted in SE programs (including one previously conducted by this research
      group), have shown that adding the TSW program to vocational (SE) services improves work and
      cognitive outcomes compared to vocational (SE) services alone.

      The proposed study takes the next bold step of "dismantling" the TSW program to evaluate
      whether the cognitive practice exercises component is critical to improving outcomes in SE,
      or whether a more streamlined and efficient version of the program that focuses only on
      teaching compensatory skills is sufficient. The study will also yield important information
      about whether some consumers benefit from computer cognitive exercises, but not others,
      permitting the TSW program to be individually tailored to consumers' personal needs.

      In preparation for the proposed study we developed, standardized, and pilot tested a variant
      of the TSW program, the Cognitive Skills for Work (CSW) program, that teaches compensatory
      skills for managing cognitive difficulties but omits computer cognitive exercises, resulting
      in a program that is approximately one-half the intensity of the original TSW program. A
      small ongoing pilot study indicated that consumers in SE could be readily engaged and
      retained in the CSW program and obtain work, supporting the feasibility of this streamlined
      version of TSW. The proposed research will be an RCT conducted at two high fidelity SE
      programs, comparing the effects of the TSW and CSW programs in consumers enrolled in SE.

      The following hypotheses will be tested:

      Primary Hypothesis: Participants in TSW will have better competitive work outcomes than those
      in the CSW program. This hypothesis is based on the fact that virtually all cognitive
      remediation research on SMI has included cognitive exercises designed to restore cognitive
      skills, such as the computer-based cognitive exercises in TSW, with some programs also
      teaching compensatory strategies. If the null hypothesis is not rejected, and TSW is found to
      be not significantly more effective than CSW, then dissemination efforts can focus on the
      more efficient CSW.

      Secondary Hypothesis: Participants in TSW will improve more in cognitive functioning than
      those in CSW. This hypothesis is based on the same rationale as Hypothesis #1.

      Exploratory Analyses: In addition to evaluating whether the TSW and CSW programs differ
      overall in their impact on vocational and cognitive outcomes, we will explore whether
      consumer characteristics can be identified that predict a differential response to either
      program. For example, it is possible that consumers with more severe cognitive impairment
      will respond better to the full TSW program, whereas those with less severe impairment may
      benefit equally well from the more efficient CSW program.

      The proposed research has high potential impact for improving the outcomes of SE, an
      established EBP for increasing competitive work in SMI, but whose effectiveness is limited by
      the extent of consumers' cognitive impairment. Maximizing the efficiency of the TSW program,
      a cognitive remediation program shown to improve work outcomes in two RCTs of SE programs, by
      determining whether a more streamlined version of the program that requires about one-half
      the time to implement (the CSW program) is equally effective, could reduce the costs of
      disseminating and implementing the program, making it accessible to more consumers. This
      study could also help identify which consumers benefit most from the cognitive exercises
      component of TSW, thereby facilitating tailoring of the program to the individual's personal
      needs. Ultimately, this research could play a critical role in making the dream of
      competitive work a reality for many consumers with SMI.

      In addition, a supplementary study, commencing in September 2015, will assess a promising
      biomarker for understanding the mechanisms underlying the effects of cognitive remediation,
      brain-derived neurotrophic factor (BDNF), in new enrollees in the parent R01 study. BDNF is a
      widely distributed protein throughout the central nervous system that promotes neuronal
      growth and is associated with a broad range of cognitive functions. Limited research suggests
      that cognitive remediation increases serum BDNF levels, including one study of schizophrenia
      and another study of Parkinson's disease. This supplemental study will provide a test of
      whether computerized cognitive training contributes to increased BDNF levels, and whether
      increases in BDNF are associated with improved cognitive functioning. The supplement will
      take advantage of the ongoing parent R01 study of the TSW program by measuring BDNF levels at
      baseline, following delivery of computerized cognitive training/teaching coping skills (6-8
      months after baseline), and at two follow-ups (16 and 24 months after baseline) in a
      diagnostically heterogeneous sample of 38 consumers with impaired cognitive functioning. This
      supplement will complement the aims of the parent R01 by shedding light on possible
      mechanisms related to how TSW works and for whom, thereby informing efforts to refine and
      improve the program, as well as targeting individuals who fail to benefit.

      The supplementary study will test the following hypotheses:

      Primary Hypothesis: Participants in TSW will show greater increases in BDNF levels from
      baseline to post-training than participants in CSW. This hypothesis is based on the
      expectation that the computerized cognitive training exercises in TSW will lead to greater
      improvements in cognitive functioning than training in compensatory strategies only in CSW,
      with increases in BDNF levels associated with improved cognitive performance. We also expect
      that greater increases in BDNF for the TSW group will be maintained at the 16- and 24 month
      follow-up assessments.

      Secondary Hypotheses: 1.) Greater improvements in cognitive functioning from baseline to the
      post-training and follow-up assessments in TSW than CSW will be associated with stronger
      increases in BDNF levels over the same assessment points. This hypothesis tests whether
      greater gains in BDNF levels for TSW mediate the long-term and sustained improvements in
      cognitive functioning for this program compare to CSW. 2.) Lower baseline BDNF levels will be
      associated with less gain in cognitive functioning for TSW. This hypothesis tests whether
      baseline BDNF levels moderate the effectiveness of TSW on improving cognitive functioning,
      with lower BDNF levels predicting less benefit. BDNF could both be found to be both a
      mediator and a moderator of the effects of cognitive remediation on improving cognitive
      functioning.

      The supplement will take place at the same sites as the parent R01: Thresholds Inc. in
      Chicago, and the Mental Health Center of Greater Manchester, NH. Inclusion and exclusion
      criteria for the supplemental sub-study are identical to those for parent R01 study. As
      before, pregnancy is not a rule out for participation in the BDNF supplement study.
      Phlebotomists associated with each site will draw one tablespoon of blood from clients at
      each assessment timepoint, therefore, a total of up to four (4) tablespoons of blood might be
      drawn from each client over the course of the study. Drawing BDNF specimens over the full
      24-month course of the study will permit researchers to address several important questions
      regarding the role of BDNF in contributing to neurocognitive functioning, both in response to
      cognitive remediation as well as how it interacts with cognitive challenging environmental
      demands-work.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: AMOUNT OF EMPLOYMENT
time frame: 24 MONTHS
description: TOTAL HOURS OF EMPLOYMENT FROM BASELINE TO 24 MONTHS. TOTAL WEEKS OF EMPLOYMENT FROM BASELINE TO 24 MONTHS. TOTAL NUMBER OF JOBS HELD FROM BASELINE TO 24 MONTHS.
measure: EXECUTIVE FUNCTIONING AND MEMORY
time frame: BASELINE, 8, 16, and 24 months.
description: CHANGE FROM BASELINE IN EXECUTIVE FUNCTIONING AND MEMORY AT 8 MONTHS USING THE MATRICS COGNITIVE ASSESSMENT BATTERY.
CHANGE FROM BASELINE IN EXECUTIVE FUNCTIONING AND MEMORY AT 16 MONTHS USING THE MATRICS COGNITIVE ASSESSMENT BATTERY.
CHANGE FROM BASELINE IN EXECUTIVE FUNCTIONING AND MEMORY AT 24 MONTHS USING THE MATRICS COGNITIVE ASSESSMENT BATTERY.
measure: BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) - AS PART OF SUPPLEMENTAL SUB-STUDY
time frame: BASELINE, 8, 16, and 24 months.
description: CHANGE FROM BASELINE IN LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AT 8 MONTHS USING ABCAM'S BDNF HUMAN ELISA (ENZYME-LINKED IMMUNOSORBENT ASSAY) KIT.
CHANGE FROM BASELINE IN LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AT 16 MONTHS USING ABCAM'S BDNF HUMAN ELISA (ENZYME-LINKED IMMUNOSORBENT ASSAY) KIT.
CHANGE FROM BASELINE IN LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AT 24 MONTHS USING ABCAM'S BDNF HUMAN ELISA (ENZYME-LINKED IMMUNOSORBENT ASSAY) KIT.
arm group label: The Thinking Skills for Work Program
arm group type: Experimental
description: The Thinking Skills for Work Program includes 5 components delivered by a Cognitive Specialist who works collaboratively with the consumer's Employment Specialist: a) assessing the consumer's strengths and weaknesses in cognitive functioning, and analysis of the contribution of cognitive impairments and other factors to job losses and difficulties obtaining a job; b) teaching coping strategies for dealing with cognitive challenges associated with job search or maintaining a job; c) computer cognitive training involving cognitive exercises with a commercially available software program, which is designed to improve the broad range of cognitive skills through a combination of practice and strategy coaching by the Cognitive Specialist; d) job search planning; and e) job support consultation.
arm group label: The Cognitive Skills for Work Program
arm group type: Active Comparator
description: The Cognitive Skills for Work Program includes 4 components delivered by a Cognitive Specialist who works with the consumer's Employment Specialist: a) assessing the consumer's cognitive strengths and weaknesses their relation to job history b) teaching coping strategies for cognitive challenges associated with job search or maintenance c)job search planning, in which the consumer and the Cognitive and Employment Specialists help identify job leads based on the consumer's interests, and identify cognitive coping strategies and supports the consumer may need to succeed at the workplace; and d) job support consultation, in which the Cognitive and Employment Specialists consult with the consumer on additional cognitive coping strategies to enable the consumer to meet the demands of the job.
intervention type: Behavioral
intervention name: The Thinking Skills for Work Program
description: The Thinking Skills for Work includes assessment of cognitive strengths and weaknesses and their relationship with work history, computerized cognitive practice, compensatory strategy training, and integration of cognitive and work services.
arm group label: The Thinking Skills for Work Program
intervention type: Behavioral
intervention name: The Cognitive Skills for Work Program
description: The Cognitive Skills for Work includes assessment of cognitive strengths and weaknesses and their relationship with work history, compensatory strategy training, and integration of cognitive and work services.
arm group label: The Cognitive Skills for Work Program
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Susan McGurk, Ph.D.
role: Principal Investigator
affiliation: Center for Psychiatric Rehabilitation, Boston University
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Boston University
investigator full name: Susan Mcgurk
investigator title: Associate Professor
mesh term: Schizophrenia
mesh term: Bipolar Disorder
mesh term: Mental Disorders
mesh term: Psychotic Disorders
sharing ipd: No