<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/NCT04418570</url>
  </required_header>
  <id_info>
    <org_study_id>PI15/01386</org_study_id>
    <nct_id>NCT04418570</nct_id>
  </id_info>
  <brief_title>Hormonal and Inflammatory Biomarkers and Response to Cognitive Remediation in Recent-onset Psychosis</brief_title>
  <official_title>Hormonal and Inflammatory Biomarkers and Response to a Cognitive Remediation Therapy in Recent-onset Psychosis: Randomized, Cross-over, Single-blind, Pilot Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Corporacion Parc Tauli</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Instituto de Salud Carlos III</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Corporacion Parc Tauli</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to explore whether hormones or inflammatory markers are associated with&#xD;
      cognitive changes following cognitive remediation therapy (CRT) in people with a recent-onset&#xD;
      psychotic disorder.&#xD;
&#xD;
      The following biomarkers for treatment response will be considered: hormones related to the&#xD;
      hypothalamic-pituitary-adrenal (HPA) axis (plasma cortisol, cortisol awakening response,&#xD;
      diurnal cortisol slope, salivary cortisol at assessment), free thyroxine (F-T4), prolactin,&#xD;
      or inflammatory markers.&#xD;
&#xD;
      This study was designed as a pilot clinical trial in order to know the feasibility of the&#xD;
      intervention and to calculate the effect sizes of different hormonal and inflammatory&#xD;
      variables on cognition. This approach would allow the design of future larger clinical trials&#xD;
      to test specific hypotheses generated with this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cognitive dysfunction is a core feature of schizophrenia experienced by approximately 75% of&#xD;
      the patients. It may occur at the early stages of psychosis, and it is usually unaltered&#xD;
      despite positive symptom remission. Cognitive function at psychosis onset is what most&#xD;
      strongly predicts worse long-term overall functioning as well as worse functionality in&#xD;
      social and occupational areas. Cognitive remediation therapy (CRT) is an intervention&#xD;
      targeting cognitive deficit using scientific principles of learning with the ultimate goal of&#xD;
      improving functional outcomes. It has been shown to have a significant impact on cognition&#xD;
      with medium effect sizes. Some studies have shown improvements in recent-onset psychosis&#xD;
      patients reporting moderate to large effects on cognitive outcomes, such as verbal and&#xD;
      working memory, visuospatial ability, psychosocial functioning, problem-solving, or executive&#xD;
      functioning.&#xD;
&#xD;
      Although CRT is an effective approach, there are data showing that 25-44% of the participants&#xD;
      receiving this intervention will not improve. To date, only a limited number of studies have&#xD;
      considered potential biomarkers that could predict the treatment response. Hormones and&#xD;
      inflammatory markers are potential biomarkers that could moderate the response to CRT because&#xD;
      they play important roles in cognitive function in psychiatric and non-psychiatric&#xD;
      populations. Previous studies have suggested that hypothalamic-pituitary-adrenal axis&#xD;
      hormones (e.g. cortisol), prolactin, thyroid hormones, and inflammatory markers are&#xD;
      associated with cognitive performance.&#xD;
&#xD;
      Twenty-eight patients with a recent-onset psychosis aged between 18 and 40 years old and with&#xD;
      less than 3 years of duration of the illness will be recruited. Psychotic disorders will&#xD;
      include the following DSM-IV diagnosis: schizophrenia, schizoaffective disorder, bipolar&#xD;
      disorder, or psychotic disorder not otherwise specified. The patients will be recruited from&#xD;
      the Early Intervention Service from Hospital Universitari Parc Taulí Sabadell, (Spain). All&#xD;
      participants will be outpatients with stable illness (&lt;4 points in each positive item of the&#xD;
      Positive and Negative Syndrome Scale (PANSS) and being on community treatment for at least 4&#xD;
      weeks).&#xD;
&#xD;
      A randomized crossover clinical trial will be performed: one group will first receive&#xD;
      computerized CRT (n=14) for three months, and the other group will receive treatment as usual&#xD;
      (TAU) in the Early Intervention Service (n=14). Afterward, patients will switch arms to&#xD;
      receive alternative intervention.&#xD;
&#xD;
      The intervention will consist of a computerized CRT through Neuropersonal Trainer software&#xD;
      (Fernandez-Gonzalo et al. 2015). This includes two rehabilitation modules: 1) the Cognition&#xD;
      Module, that addresses the following cognitive domains: on sustained, selective and divided&#xD;
      attention; verbal, spatial, visual and working memory; and executive functions including&#xD;
      inhibition, sequence and planning; and 2) the Social Cognition Module, which allows working&#xD;
      different aspects of emotional processing, the theory of mind and cognitive biases through 43&#xD;
      multimedia-based tasks. Both modules have different levels of complexity. Each CRT session&#xD;
      will be individualized to the cognitive needs of each patient by an expert neuropsychologist.&#xD;
      The professional can adjust the difficulty level in each treatment session based on the&#xD;
      participant baseline cognitive profile and his/her task performance in previous treatment&#xD;
      sessions. The neuropsychologist will be guiding the sessions, assuring the understanding of&#xD;
      the different tasks, and individually coaching every patient to achieve the correct&#xD;
      performance.&#xD;
&#xD;
      A fasting morning blood sample (drawn between 8 a.m. and 10 a.m.) will be obtained for all&#xD;
      participants at baseline, at 12 weeks and at 24 weeks of follow-up, for determining cortisol,&#xD;
      prolactin, hypothalamic-pituitary-thyroid axis hormones (thyroid-stimulating hormone [TSH]&#xD;
      and free thyroxine [F-T4]), and inflammatory markers (IL-6, TNF-alpha, leukocyte count).&#xD;
      Saliva samples will be collected for exploring hypothalamic-pituitary-adrenal axis measures&#xD;
      (cortisol awakening response, circadian cortisol slope, cortisol levels at cognitive&#xD;
      assessment) at each visit (baseline, week 12, and week 24).&#xD;
&#xD;
      Repeated measurements at the same time points will be obtained with a neurocognitive battery&#xD;
      based on the CANTAB cognitive battery for schizophrenia, that includes 8 cognitive tasks:&#xD;
      Attention Switching Task (AST; assessing attention and response latencies); One Touch&#xD;
      Stockings of Cambridge (OTS; assessing executive functioning: spatial planning and working&#xD;
      memory); Paired Associates Learning (PAL; assessing visual memory and new learning); Reaction&#xD;
      Time (RTI; assessing reaction time: motor and mental response speeds, as well as measures of&#xD;
      movement time, reaction time, response accuracy and impulsivity); Rapid Vision Information&#xD;
      Processing (RVP; assessing sustained attention); Emotion Recognition Task (ERT; assessing&#xD;
      theory of mind processes); Spatial Working Memory (SWM; assessing Spatial Working Memory:&#xD;
      retention and manipulation of visuospatial information, strategy and working memory errors);&#xD;
      Verbal Recognition Memory (VRM; assessing verbal memory and new learning). Cognitive&#xD;
      assessment will be performed between 3 p.m. and 5 p.m. Psychopathological assessment at each&#xD;
      visit (baseline, 12 weeks and 24 weeks) will be assessed with the Positive and Negative&#xD;
      Syndromes Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). The social&#xD;
      performance will be assessed at each visit with the Personal Performance Scale (PSP).&#xD;
      Assessments will be conducted by trained personnel who will remain blind to the group&#xD;
      assignment.&#xD;
&#xD;
      Linear mixed models will be used to explore whether hormonal or inflammatory biomarkers are&#xD;
      associated with cognitive changes after the intervention (CRT). The model will test the fixed&#xD;
      effects for the intervention (CRT vs TAU), time (baseline visit vs 3-month visit), and the&#xD;
      studied hormones, as well as their interactions. Random effects will be considered for each&#xD;
      participant. Two analyses will be conducted:&#xD;
&#xD;
        1. Primary analysis: randomized parallel phase (intention-to-treat analysis; CRT vs TAU;&#xD;
           first 3 months).&#xD;
&#xD;
           All participants will be included, independently of whether they completed CRT or not.&#xD;
&#xD;
        2. Secondary analysis: pre-post changes in CRT (per-protocol analysis; CRT only; 3 months).&#xD;
&#xD;
      This secondary analysis will include a subgroup of patients who have completed at least&#xD;
      one-third of the CRT sessions. For this analysis, those patients receiving CRT in the first&#xD;
      wave (randomized parallel phase) or second wave (after the cross-over) will be grouped.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2016</start_date>
  <completion_date type="Actual">March 2020</completion_date>
  <primary_completion_date type="Actual">March 2020</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>Crossover Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma cortisol concentrations</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma cortisol concentrations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cortisol awakening response</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and the cortisol awakening response.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Diurnal cortisol slope</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and the diurnal cortisol slope (calculated as the slope between salivary cortisol between awakening and 23h).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cortisol at neuropsychological assessment</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and salivary cortisol at neuropsychological assessment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma prolactin concentrations</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma prolactin concentrations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma free thyroxine (F-T4) concentrations</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma F-T4 concentrations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neutrophil to lymphocyte ratio</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and neutrophil to lymphocyte ratio.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma interleukin-6 concentrations</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma interleukin-6 concentrations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma tumor necrosis factor alpha (TNF-alpha) concentrations</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma TNF-alpha concentrations.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma cortisol after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>Morning plasma cortisol concentrations will be determined. The investigators will examine longitudinal changes in plasma cortisol concentrations after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the cortisol awakening response after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>The cortisol awakening response will be measured in saliva. The investigators will examine longitudinal changes in the cortisol awakening response after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the diurnal cortisol slope after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>Salivary cortisol measures will be obtained at awakening and at 23h. The diurnal cortisol slope will be calculated between awakening and 23h. The investigators will examine longitudinal changes in the diurnal cortisol slope after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cortisol concentrations at neuropsychological assessment after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>Salivary cortisol concentrations at neuropsychological assessment will be determined. The investigators will examine longitudinal changes in cortisol concentrations at neuropsychological assessment after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma prolactin concentrations after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>Plasma prolactin concentrations will be determined in the morning. The investigators will examine longitudinal changes in prolactin concentrations after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma free thyroxine (F-T4) concentrations after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>Plasma F-T4 concentrations will be determined in the morning. The investigators will examine longitudinal changes in F-T4 concentrations after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in neutrophil to lymphocyte ratio after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>Leukocyte count will be measured in plasma and the neutrophil to lymphocyte ratio will be calculated. The investigators will examine longitudinal changes in the neutrophil to lymphocyte ratio after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma interleukin-6 (IL-6) concentrations after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>IL-6 concentrations will be determined in plasma. The investigators will examine longitudinal changes in IL-6 concentrations after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma tumor necrosis factor-alpha (TNF-alpha) concentrations after a cognitive remediation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>TNF-alpha concentrations will be determined in plasma. The investigators will examine longitudinal changes in TNF-alpha concentrations after a cognitive remediation therapy.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Psychotic Disorders</condition>
  <arm_group>
    <arm_group_label>Cognitive remediation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Computerized cognitive remediation through Neuropersonal Trainer software, 1.5 h per session twice a week for 12 weeks (36 h of total duration).&#xD;
Participants will also attend the Early Intervention Service for Psychosis with visits by a psychiatrist, clinical psychologist, social worker, or nurse as scheduled.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment as usual</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants will attend the Early Intervention Service for Psychosis with visits by a psychiatrist, clinical psychologist, social worker, or nurse as scheduled.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>cognitive remediation</intervention_name>
    <arm_group_label>Cognitive remediation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>attendance to an Early Intervention Service for Psychosis</intervention_name>
    <arm_group_label>Cognitive remediation</arm_group_label>
    <arm_group_label>Treatment as usual</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Psychotic disorder meeting Diagnostic and Statistical Manual of Mental Disorders - 4th&#xD;
             edition (DSM-IV) criteria for any of the following diagnoses: schizophrenia,&#xD;
             schizoaffective disorder, bipolar disorder, and psychotic disorder not otherwise&#xD;
             specified.&#xD;
&#xD;
          -  Recent-onset psychosis (&lt; 3 years of illness).&#xD;
&#xD;
          -  Outpatients with stable illness (&lt;4 points in each positive item of the Positive and&#xD;
             Negative Syndrome Scale [PANSS]).&#xD;
&#xD;
          -  Being on community treatment for at least 4 weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to participate.&#xD;
&#xD;
          -  Severe neurological disease or intellectual disability.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Substance-induced psychosis.&#xD;
&#xD;
          -  History of severe traumatic brain injury.&#xD;
&#xD;
          -  Current treatment with glucocorticoids.&#xD;
&#xD;
          -  Visual deficits or language difficulties that could influence cognitive assessment and&#xD;
             intervention.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Javier Labad, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parc Taulí Hospital Universitari, Sabadell, Barcelona (Spain).</affiliation>
  </overall_official>
  <reference>
    <citation>Fernandez-Gonzalo S, Turon M, Jodar M, Pousa E, Hernandez Rambla C, Garcia R, Palao D. A new computerized cognitive and social cognition training specifically designed for patients with schizophrenia/schizoaffective disorder in early stages of illness: A pilot study. Psychiatry Res. 2015 Aug 30;228(3):501-9. doi: 10.1016/j.psychres.2015.06.007. Epub 2015 Jun 18.</citation>
    <PMID>26163731</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>June 4, 2020</last_update_submitted>
  <last_update_submitted_qc>June 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Corporacion Parc Tauli</investigator_affiliation>
    <investigator_full_name>Javier Labad</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>early psychosis</keyword>
  <keyword>cortisol</keyword>
  <keyword>inflammation</keyword>
  <keyword>thyroid</keyword>
  <keyword>prolactin</keyword>
  <keyword>cognitive rehabilitation</keyword>
  <keyword>cognitive remediation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychotic Disorders</mesh_term>
    <mesh_term>Mental 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/NCT04418570
org study id: PI15/01386
nct id: NCT04418570
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to explore whether hormones or inflammatory markers are associated with
      cognitive changes following cognitive remediation therapy (CRT) in people with a recent-onset
      psychotic disorder.

      The following biomarkers for treatment response will be considered: hormones related to the
      hypothalamic-pituitary-adrenal (HPA) axis (plasma cortisol, cortisol awakening response,
      diurnal cortisol slope, salivary cortisol at assessment), free thyroxine (F-T4), prolactin,
      or inflammatory markers.

      This study was designed as a pilot clinical trial in order to know the feasibility of the
      intervention and to calculate the effect sizes of different hormonal and inflammatory
      variables on cognition. This approach would allow the design of future larger clinical trials
      to test specific hypotheses generated with this study.
Cognitive dysfunction is a core feature of schizophrenia experienced by approximately 75% of
      the patients. It may occur at the early stages of psychosis, and it is usually unaltered
      despite positive symptom remission. Cognitive function at psychosis onset is what most
      strongly predicts worse long-term overall functioning as well as worse functionality in
      social and occupational areas. Cognitive remediation therapy (CRT) is an intervention
      targeting cognitive deficit using scientific principles of learning with the ultimate goal of
      improving functional outcomes. It has been shown to have a significant impact on cognition
      with medium effect sizes. Some studies have shown improvements in recent-onset psychosis
      patients reporting moderate to large effects on cognitive outcomes, such as verbal and
      working memory, visuospatial ability, psychosocial functioning, problem-solving, or executive
      functioning.

      Although CRT is an effective approach, there are data showing that 25-44% of the participants
      receiving this intervention will not improve. To date, only a limited number of studies have
      considered potential biomarkers that could predict the treatment response. Hormones and
      inflammatory markers are potential biomarkers that could moderate the response to CRT because
      they play important roles in cognitive function in psychiatric and non-psychiatric
      populations. Previous studies have suggested that hypothalamic-pituitary-adrenal axis
      hormones (e.g. cortisol), prolactin, thyroid hormones, and inflammatory markers are
      associated with cognitive performance.

      Twenty-eight patients with a recent-onset psychosis aged between 18 and 40 years old and with
      less than 3 years of duration of the illness will be recruited. Psychotic disorders will
      include the following DSM-IV diagnosis: schizophrenia, schizoaffective disorder, bipolar
      disorder, or psychotic disorder not otherwise specified. The patients will be recruited from
      the Early Intervention Service from Hospital Universitari Parc Taulí Sabadell, (Spain). All
      participants will be outpatients with stable illness (<4 points in each positive item of the
      Positive and Negative Syndrome Scale (PANSS) and being on community treatment for at least 4
      weeks).

      A randomized crossover clinical trial will be performed: one group will first receive
      computerized CRT (n=14) for three months, and the other group will receive treatment as usual
      (TAU) in the Early Intervention Service (n=14). Afterward, patients will switch arms to
      receive alternative intervention.

      The intervention will consist of a computerized CRT through Neuropersonal Trainer software
      (Fernandez-Gonzalo et al. 2015). This includes two rehabilitation modules: 1) the Cognition
      Module, that addresses the following cognitive domains: on sustained, selective and divided
      attention; verbal, spatial, visual and working memory; and executive functions including
      inhibition, sequence and planning; and 2) the Social Cognition Module, which allows working
      different aspects of emotional processing, the theory of mind and cognitive biases through 43
      multimedia-based tasks. Both modules have different levels of complexity. Each CRT session
      will be individualized to the cognitive needs of each patient by an expert neuropsychologist.
      The professional can adjust the difficulty level in each treatment session based on the
      participant baseline cognitive profile and his/her task performance in previous treatment
      sessions. The neuropsychologist will be guiding the sessions, assuring the understanding of
      the different tasks, and individually coaching every patient to achieve the correct
      performance.

      A fasting morning blood sample (drawn between 8 a.m. and 10 a.m.) will be obtained for all
      participants at baseline, at 12 weeks and at 24 weeks of follow-up, for determining cortisol,
      prolactin, hypothalamic-pituitary-thyroid axis hormones (thyroid-stimulating hormone [TSH]
      and free thyroxine [F-T4]), and inflammatory markers (IL-6, TNF-alpha, leukocyte count).
      Saliva samples will be collected for exploring hypothalamic-pituitary-adrenal axis measures
      (cortisol awakening response, circadian cortisol slope, cortisol levels at cognitive
      assessment) at each visit (baseline, week 12, and week 24).

      Repeated measurements at the same time points will be obtained with a neurocognitive battery
      based on the CANTAB cognitive battery for schizophrenia, that includes 8 cognitive tasks:
      Attention Switching Task (AST; assessing attention and response latencies); One Touch
      Stockings of Cambridge (OTS; assessing executive functioning: spatial planning and working
      memory); Paired Associates Learning (PAL; assessing visual memory and new learning); Reaction
      Time (RTI; assessing reaction time: motor and mental response speeds, as well as measures of
      movement time, reaction time, response accuracy and impulsivity); Rapid Vision Information
      Processing (RVP; assessing sustained attention); Emotion Recognition Task (ERT; assessing
      theory of mind processes); Spatial Working Memory (SWM; assessing Spatial Working Memory:
      retention and manipulation of visuospatial information, strategy and working memory errors);
      Verbal Recognition Memory (VRM; assessing verbal memory and new learning). Cognitive
      assessment will be performed between 3 p.m. and 5 p.m. Psychopathological assessment at each
      visit (baseline, 12 weeks and 24 weeks) will be assessed with the Positive and Negative
      Syndromes Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). The social
      performance will be assessed at each visit with the Personal Performance Scale (PSP).
      Assessments will be conducted by trained personnel who will remain blind to the group
      assignment.

      Linear mixed models will be used to explore whether hormonal or inflammatory biomarkers are
      associated with cognitive changes after the intervention (CRT). The model will test the fixed
      effects for the intervention (CRT vs TAU), time (baseline visit vs 3-month visit), and the
      studied hormones, as well as their interactions. Random effects will be considered for each
      participant. Two analyses will be conducted:

        1. Primary analysis: randomized parallel phase (intention-to-treat analysis; CRT vs TAU;
           first 3 months).

           All participants will be included, independently of whether they completed CRT or not.

        2. Secondary analysis: pre-post changes in CRT (per-protocol analysis; CRT only; 3 months).

      This secondary analysis will include a subgroup of patients who have completed at least
      one-third of the CRT sessions. For this analysis, those patients receiving CRT in the first
      wave (randomized parallel phase) or second wave (after the cross-over) will be grouped.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Diagnostic
masking: Single (Outcomes Assessor)
measure: Plasma cortisol concentrations
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma cortisol concentrations.
measure: Cortisol awakening response
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and the cortisol awakening response.
measure: Diurnal cortisol slope
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and the diurnal cortisol slope (calculated as the slope between salivary cortisol between awakening and 23h).
measure: Cortisol at neuropsychological assessment
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and salivary cortisol at neuropsychological assessment.
measure: Plasma prolactin concentrations
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma prolactin concentrations.
measure: Plasma free thyroxine (F-T4) concentrations
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma F-T4 concentrations.
measure: Neutrophil to lymphocyte ratio
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and neutrophil to lymphocyte ratio.
measure: Plasma interleukin-6 concentrations
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma interleukin-6 concentrations.
measure: Plasma tumor necrosis factor alpha (TNF-alpha) concentrations
time frame: 3 months
description: Correlation between cognitive changes, assessed with the CANTAB Cognitive battery for schizophrenia, and plasma TNF-alpha concentrations.
measure: Changes in plasma cortisol after a cognitive remediation therapy
time frame: 3 months
description: Morning plasma cortisol concentrations will be determined. The investigators will examine longitudinal changes in plasma cortisol concentrations after a cognitive remediation therapy.
measure: Changes in the cortisol awakening response after a cognitive remediation therapy
time frame: 3 months
description: The cortisol awakening response will be measured in saliva. The investigators will examine longitudinal changes in the cortisol awakening response after a cognitive remediation therapy.
measure: Changes in the diurnal cortisol slope after a cognitive remediation therapy
time frame: 3 months
description: Salivary cortisol measures will be obtained at awakening and at 23h. The diurnal cortisol slope will be calculated between awakening and 23h. The investigators will examine longitudinal changes in the diurnal cortisol slope after a cognitive remediation therapy.
measure: Changes in cortisol concentrations at neuropsychological assessment after a cognitive remediation therapy
time frame: 3 months
description: Salivary cortisol concentrations at neuropsychological assessment will be determined. The investigators will examine longitudinal changes in cortisol concentrations at neuropsychological assessment after a cognitive remediation therapy.
measure: Changes in plasma prolactin concentrations after a cognitive remediation therapy
time frame: 3 months
description: Plasma prolactin concentrations will be determined in the morning. The investigators will examine longitudinal changes in prolactin concentrations after a cognitive remediation therapy.
measure: Changes in plasma free thyroxine (F-T4) concentrations after a cognitive remediation therapy
time frame: 3 months
description: Plasma F-T4 concentrations will be determined in the morning. The investigators will examine longitudinal changes in F-T4 concentrations after a cognitive remediation therapy.
measure: Changes in neutrophil to lymphocyte ratio after a cognitive remediation therapy
time frame: 3 months
description: Leukocyte count will be measured in plasma and the neutrophil to lymphocyte ratio will be calculated. The investigators will examine longitudinal changes in the neutrophil to lymphocyte ratio after a cognitive remediation therapy.
measure: Changes in plasma interleukin-6 (IL-6) concentrations after a cognitive remediation therapy
time frame: 3 months
description: IL-6 concentrations will be determined in plasma. The investigators will examine longitudinal changes in IL-6 concentrations after a cognitive remediation therapy.
measure: Changes in plasma tumor necrosis factor-alpha (TNF-alpha) concentrations after a cognitive remediation therapy
time frame: 3 months
description: TNF-alpha concentrations will be determined in plasma. The investigators will examine longitudinal changes in TNF-alpha concentrations after a cognitive remediation therapy.
arm group label: Cognitive remediation
arm group type: Experimental
description: Computerized cognitive remediation through Neuropersonal Trainer software, 1.5 h per session twice a week for 12 weeks (36 h of total duration).
Participants will also attend the Early Intervention Service for Psychosis with visits by a psychiatrist, clinical psychologist, social worker, or nurse as scheduled.
arm group label: Treatment as usual
arm group type: Other
description: Participants will attend the Early Intervention Service for Psychosis with visits by a psychiatrist, clinical psychologist, social worker, or nurse as scheduled.
intervention type: Behavioral
intervention name: cognitive remediation
arm group label: Cognitive remediation
intervention type: Other
intervention name: attendance to an Early Intervention Service for Psychosis
arm group label: Cognitive remediation
arm group label: Treatment as usual
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Javier Labad, M.D., Ph.D.
role: Principal Investigator
affiliation: Parc Taulí Hospital Universitari, Sabadell, Barcelona (Spain).
citation: Fernandez-Gonzalo S, Turon M, Jodar M, Pousa E, Hernandez Rambla C, Garcia R, Palao D. A new computerized cognitive and social cognition training specifically designed for patients with schizophrenia/schizoaffective disorder in early stages of illness: A pilot study. Psychiatry Res. 2015 Aug 30;228(3):501-9. doi: 10.1016/j.psychres.2015.06.007. Epub 2015 Jun 18.
PMID: 26163731
responsible party type: Principal Investigator
investigator affiliation: Corporacion Parc Tauli
investigator full name: Javier Labad
investigator title: Principal investigator
mesh term: Psychotic Disorders
mesh term: Mental Disorders
sharing ipd: No