<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/NCT02218853</url>
  </required_header>
  <id_info>
    <org_study_id>MH077851</org_study_id>
    <secondary_id>1R01MH096913-01A1</secondary_id>
    <nct_id>NCT02218853</nct_id>
  </id_info>
  <brief_title>Psychosis and Affective Research Domains and Intermediate Phenotypes</brief_title>
  <acronym>PARDIP</acronym>
  <official_title>Psychosis and Affective Research Domains and Intermediate Phenotypes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beth Israel Deaconess Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hartford Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Georgia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this multi-site research collaboration is to test the manifestation and&#xD;
      distribution of biological markers for psychosis and affect dimensions across the&#xD;
      schizophrenia/bipolar (SZ-BD) diagnostic boundary, and to examine heritability and genetic&#xD;
      associations for these biological markers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The B-SNIP research consortium previously obtained dense phenotypes across the psychosis&#xD;
      spectrum in an effort to observe features both (i) distinctive to and (ii) shared between&#xD;
      DSM-type categorical diagnoses. Despite the broad range of extra-clinical phenotypes, we had&#xD;
      limited success finding clinical SZ-BD diagnosis-specific features; instead, most phenotypes&#xD;
      were distributed continuously across DSM diagnoses. To describe more biologically homogeneous&#xD;
      groups, therefore, we combined all psychosis probands and implemented a multi-stage analysis&#xD;
      procedure, beginning with identification of psychosis biomarkers (variables with the largest&#xD;
      effect sizes for differentiating psychosis and healthy groups) including cognitive,&#xD;
      electrophysiological, and oculo-motor measures ('classical' endophenotypes). We then&#xD;
      estimated the number of subgroups that efficiently optimized variance among the biomarkers&#xD;
      (n=3) and differentiated the individual psychosis cases into these subgroups. Subsequently,&#xD;
      the subgroups were tested for biological uniqueness using meaningful external validators&#xD;
      (structural and functional brain imaging, social functioning, and familial data). Given the&#xD;
      neurobiological distinctiveness of these subgroups, we called them psychosis Biotypes. DSM&#xD;
      diagnoses were distributed across all Biotypes. Compared to DSM diagnoses, Biotype membership&#xD;
      enhanced group separations on biomarkers. These results indicate that groups of psychosis&#xD;
      cases can be generated with homogeneous phenotypic characteristics independent of DSM&#xD;
      diagnoses. The proposed study aims to further develop Biotype definitions and demonstrate&#xD;
      that psychosis Biotypes constructed from a dense biomarker panel (i) are replicable, (ii)&#xD;
      neurobiologically distinctive, and (iii) have unique genetic characteristics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls on functional and structural brain imaging, neurocognitive assessments, and neurophysiological tests</measure>
    <time_frame>One day</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls on clinical assessment questionnaires</measure>
    <time_frame>One day</time_frame>
    <description>The investigators will assess clustering of probands and relatives across composite biomarkers independent of diagnostic status using multivariate taxometric procedures.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls in DNA and dermal biopsy sampling</measure>
    <time_frame>One day</time_frame>
    <description>The investigators will collect DNA from all proband and relative subjects and collaboratively sequence the genetic material to associate genes with specific biomarkers and composite Biotype definitions. We will also collect plasma and cellular specimens to bank for analysis of additional molecular biomarkers unique to each Biotype.</description>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">113</enrollment>
  <condition>Bipolar I Disorder, Unspecified, With Psychotic Features</condition>
  <condition>Bipolar I Disorder, Unspecified, Without Psychotic Features</condition>
  <arm_group>
    <arm_group_label>Bipolar I disorder, with psychosis</arm_group_label>
    <description>Individuals diagnosed with Bipolar I disorder, with psychotic features</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bipolar I disorder, without psychosis</arm_group_label>
    <description>Individuals diagnosed with Bipolar I disorder, without psychotic features</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>Must have no personal history of any psychotic or mood disorder, or a family history of psychotic or recurrent mood disorder among their first-degree relatives</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA will be extracted from blood (or buccal swab) and stored at the UT Southwestern Human&#xD;
      Genetic Center in a departmental freezer at -80 degrees. Part of the blood sample will be&#xD;
      used to create an immortalized lymphocyte culture (a lymphoblastoid cell line) for future&#xD;
      genetic analysis, and will be stored in a Cell Bank at the UT Southwestern Human Genetic&#xD;
      Center. The blood samples will be labeled by a coded identifier (number) and will not be&#xD;
      personally identifiable. Only specifically designated research staff from Dr. Tamminga's&#xD;
      group and from the UT Southwestern Human Genetic Center will have an access to stored DNA&#xD;
      samples. All samples will be de-identified. The genetic data will be in password-protected&#xD;
      computers in the Investigators' research offices.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will be comprised of individuals between the ages of 18-60 years old&#xD;
        who meet DSM-IV criteria for Bipolar I disorder, read/speak/understand the English&#xD;
        language, and are deemed capable of completing the study procedures by the research&#xD;
        investigators.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must provide consent to participate after being fully informed about the study&#xD;
             procedures and the information to be collected&#xD;
&#xD;
          -  Males and females&#xD;
&#xD;
          -  Ages 18-60 years old&#xD;
&#xD;
          -  All races and ethnicities&#xD;
&#xD;
          -  Probands: Must meet DSM-IV criteria for bipolar I disorder with or without lifetime&#xD;
             history of psychosis; Healthy Controls: Must have no personal history of any psychotic&#xD;
             or mood disorder, or a family history of psychotic or recurrent mood disorder among&#xD;
             their first-degree relatives&#xD;
&#xD;
          -  Must be judged to be capable of completing the study procedures by study investigators&#xD;
&#xD;
          -  Must be able to read, speak, and understand English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  An estimated IQ&lt;70&#xD;
&#xD;
          -  Major neurological or cognitive disorder (e.g., seizure disorder, traumatic brain&#xD;
             injury, cerebrovascular disease, pervasive developmental disorder)&#xD;
&#xD;
          -  Serious medical, neuro-ophthalmological, or neurological illness that could affect CNS&#xD;
             functioning (e.g., decompensated cardiovascular disease, decompensated chronic&#xD;
             obstructive pulmonary disease, late stages of diabetes, AIDS)&#xD;
&#xD;
          -  DSM-IV diagnosis of alcohol or illicit substance abuse within 1 month, or alcohol or&#xD;
             substance dependence within 3 months, or extensive history of past substance use&#xD;
&#xD;
          -  Women who are pregnant (due to unknown risks related to MRI exposure)&#xD;
&#xD;
          -  Presence of medical (e.g., artificial joints, brain aneurism clips, surgical pins,&#xD;
             rods, wires, implants) or non-medical (e.g., metal piercing) irremovable metallic&#xD;
             objects on/inside body (due to MRI-relevant risks)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carol A Tamminga, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.utsouthwestern.edu/labs/schizophrenia/</url>
    <description>Tamminga Lab and Clinic Website</description>
  </link>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>September 18, 2019</last_update_submitted>
  <last_update_submitted_qc>September 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bipolar disorder</keyword>
  <keyword>Psychosis</keyword>
  <keyword>Schizophrenia</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>
  <!-- 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/NCT02218853
org study id: MH077851
secondary id: 1R01MH096913-01A1
nct id: NCT02218853
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The objective of this multi-site research collaboration is to test the manifestation and
      distribution of biological markers for psychosis and affect dimensions across the
      schizophrenia/bipolar (SZ-BD) diagnostic boundary, and to examine heritability and genetic
      associations for these biological markers.
The B-SNIP research consortium previously obtained dense phenotypes across the psychosis
      spectrum in an effort to observe features both (i) distinctive to and (ii) shared between
      DSM-type categorical diagnoses. Despite the broad range of extra-clinical phenotypes, we had
      limited success finding clinical SZ-BD diagnosis-specific features; instead, most phenotypes
      were distributed continuously across DSM diagnoses. To describe more biologically homogeneous
      groups, therefore, we combined all psychosis probands and implemented a multi-stage analysis
      procedure, beginning with identification of psychosis biomarkers (variables with the largest
      effect sizes for differentiating psychosis and healthy groups) including cognitive,
      electrophysiological, and oculo-motor measures ('classical' endophenotypes). We then
      estimated the number of subgroups that efficiently optimized variance among the biomarkers
      (n=3) and differentiated the individual psychosis cases into these subgroups. Subsequently,
      the subgroups were tested for biological uniqueness using meaningful external validators
      (structural and functional brain imaging, social functioning, and familial data). Given the
      neurobiological distinctiveness of these subgroups, we called them psychosis Biotypes. DSM
      diagnoses were distributed across all Biotypes. Compared to DSM diagnoses, Biotype membership
      enhanced group separations on biomarkers. These results indicate that groups of psychosis
      cases can be generated with homogeneous phenotypic characteristics independent of DSM
      diagnoses. The proposed study aims to further develop Biotype definitions and demonstrate
      that psychosis Biotypes constructed from a dense biomarker panel (i) are replicable, (ii)
      neurobiologically distinctive, and (iii) have unique genetic characteristics.
observational model: Case-Control
time perspective: Prospective
measure: Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls on functional and structural brain imaging, neurocognitive assessments, and neurophysiological tests
time frame: One day
measure: Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls on clinical assessment questionnaires
time frame: One day
description: The investigators will assess clustering of probands and relatives across composite biomarkers independent of diagnostic status using multivariate taxometric procedures.
measure: Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls in DNA and dermal biopsy sampling
time frame: One day
description: The investigators will collect DNA from all proband and relative subjects and collaboratively sequence the genetic material to associate genes with specific biomarkers and composite Biotype definitions. We will also collect plasma and cellular specimens to bank for analysis of additional molecular biomarkers unique to each Biotype.
arm group label: Bipolar I disorder, with psychosis
description: Individuals diagnosed with Bipolar I disorder, with psychotic features
arm group label: Bipolar I disorder, without psychosis
description: Individuals diagnosed with Bipolar I disorder, without psychotic features
arm group label: Healthy Controls
description: Must have no personal history of any psychotic or mood disorder, or a family history of psychotic or recurrent mood disorder among their first-degree relatives
DNA will be extracted from blood (or buccal swab) and stored at the UT Southwestern Human
      Genetic Center in a departmental freezer at -80 degrees. Part of the blood sample will be
      used to create an immortalized lymphocyte culture (a lymphoblastoid cell line) for future
      genetic analysis, and will be stored in a Cell Bank at the UT Southwestern Human Genetic
      Center. The blood samples will be labeled by a coded identifier (number) and will not be
      personally identifiable. Only specifically designated research staff from Dr. Tamminga's
      group and from the UT Southwestern Human Genetic Center will have an access to stored DNA
      samples. All samples will be de-identified. The genetic data will be in password-protected
      computers in the Investigators' research offices.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Carol A Tamminga, M.D.
role: Principal Investigator
affiliation: UT Southwestern Medical Center
facility: 
country: United States
url: http://www.utsouthwestern.edu/labs/schizophrenia/
description: Tamminga Lab and Clinic Website
responsible party type: Sponsor
mesh term: Psychotic Disorders
mesh term: Mental Disorders