<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/NCT04469322</url>
  </required_header>
  <id_info>
    <org_study_id>H130471</org_study_id>
    <nct_id>NCT04469322</nct_id>
  </id_info>
  <brief_title>Pharmacogenetic Implementation Trial in Veterans With Treatment Refractory Depression</brief_title>
  <official_title>Pharmacogenetic Implementation Trial in Veterans With Treatment Refractory Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>San Diego Veterans Healthcare System</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>VA Palo Alto Health Care System</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>San Diego Veterans Healthcare System</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>
      Many patients with depression do not respond well to medication and are diagnosed with&#xD;
      treatment refractory depression (TRD). Sometimes medications don't work because an individual&#xD;
      metabolizes the drugs in an atypical manner (too fast/slow). Alternatively, drugs may fail to&#xD;
      work because the underlying sub-type of depression is not effectively targeted by a&#xD;
      medication. This study will use genetic testing of subjects with TRD to personalize the drug&#xD;
      treatment of depression and guide the patient to a better clinical outcome. In the guided&#xD;
      group, the clinician will receive a pharmacogenetic report to help individually tailor&#xD;
      medication selection for TRD patients, potentially allowing the clinician to pick more&#xD;
      effective medications right away, and when necessary, use drug combinations that are&#xD;
      well-tolerated and less likely to cause unwanted side effects. The control group will receive&#xD;
      a sham genetic report and be treated according to typical standards of care. The&#xD;
      investigators will conduct our study in a &quot;real world&quot; setting, with few restrictions on&#xD;
      which TRD patients can participate. In this way, the findings may be more likely to reveal&#xD;
      how useful genetic testing will be when applied more broadly in psychiatry.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design and Methods. The investigators will use prospective methods to assess the&#xD;
      utility of pharmacogenetic guided treatment (PGT) of TRD. The use of genetic testing for PGT&#xD;
      subjects, and clinical care guided by the individual's genetic results are the only subject&#xD;
      activities in this study that represent a departure from standard clinical care. Other&#xD;
      activities carried out within the context of this study are conducted in accordance with&#xD;
      accepted clinical practice by a trained and licensed psychiatrist. These include (but are not&#xD;
      limited to) the use of prescription medications, laboratory testing, vital sign measurements,&#xD;
      mood scales and diagnostic interviews, electrocardiograms, and imaging studies. Standard&#xD;
      clinical activities will be conducted at the discretion of the attending psychiatrist,&#xD;
      determined by the clinical needs of the individual patient. All laboratory testing conducted&#xD;
      for the purposes of clinical treatment (diagnosis, treatment, and prevention of illness) will&#xD;
      be conducted at the VA San Diego or VA Palo Alto accredited clinical laboratories. No&#xD;
      investigational medications or devices will be used in this study.&#xD;
&#xD;
      Setting: Clinical care will be conducted at the Veterans Affairs San Diego Healthcare System&#xD;
      and Veterans Affairs Palo Alto Healthcare . Patients with TRD will be recruited from multiple&#xD;
      sites in the local VA Systems. Clinical care will be provided by a VA psychiatrist.&#xD;
&#xD;
      Genotyping: After obtaining written consent, patients will give a saliva sample from which&#xD;
      genomic DNA is prepared using established protocols. DNA samples will be assigned a coded&#xD;
      subject identification number that will not contain any sensitive personal information. The&#xD;
      code key will remain at the VASDHS at all times. Samples will be sent to a CLIA certified&#xD;
      laboratory (Pathway Genomics) for genotyping and analyzed using the commercially available&#xD;
      Mental Health DNA Insight Test. Unused DNA sent for genotyping will be destroyed. No DNA&#xD;
      storage outside the VASDHS will be permitted. No other clinically relevant information will&#xD;
      be uncovered by the genetic testing.&#xD;
&#xD;
      Randomization &amp; Study Design: Patients will be randomly assigned to one of two groups:&#xD;
      Pharmacogenetic guided treatment (PGT) and treatment as usual (TAU). All patients will&#xD;
      provide a saliva sample at the start of their participation 5-7 days before their initial&#xD;
      clinic appointment: All subjects will be genotyped and analyzed using the Mental Health DNA&#xD;
      Insight Test. The treating physician for the PGT group will receive the report before the&#xD;
      first clinic visit. The treating physician for the TAU group will receive a sham report.&#xD;
&#xD;
      Patients will remain blind into which treatment group they are assigned until completion of&#xD;
      the study. The study physicians will not be blinded due to the need to review the PGT report.&#xD;
      However, bias will be reduced by using patient self-reports of their mood using the 16-item&#xD;
      quick inventory of depressive symptoms self report (QIDS-SR16) scale. All patients will then&#xD;
      be seen by a study psychiatrist at 4 weeks and 8 weeks follow-up. All patients will complete&#xD;
      self assessment inventories at each visit. In addition they will assess tolerability using a&#xD;
      standardized side effect checklist. Overall functional impairment and symptom severity will&#xD;
      be assessed using the Clinical Global Impressions Scale (CGI). Primary study outcome will be&#xD;
      the CGI score at the end of the study (8 weeks). A Comprehensive Suicide Risk Assessment will&#xD;
      be done at study initiation and a clinical suicidality assessment will be conducted at every&#xD;
      visit according to usual clinical practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 30, 2014</start_date>
  <completion_date type="Actual">June 26, 2018</completion_date>
  <primary_completion_date type="Actual">June 26, 2018</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>
    <intervention_model_description>randomized, single blind, multi-center, prospective</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>patient blinded to condition</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Global Impression (CGI)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression (CGI)</measure>
    <time_frame>0 weeks</time_frame>
    <description>Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression (CGI)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side Effects Burden</measure>
    <time_frame>0 weeks</time_frame>
    <description>Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side Effects Burden</measure>
    <time_frame>4 weeks</time_frame>
    <description>Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side Effects Burden</measure>
    <time_frame>8 weeks</time_frame>
    <description>Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)</measure>
    <time_frame>0 weeks</time_frame>
    <description>Self Reported Depression Symptoms (scored 1 mild - 27 severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Self Reported Depression Symptoms (scored 1 mild - 27 severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Self Reported Depression Symptoms (scored 1 mild - 27 severe)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">182</enrollment>
  <condition>Depression</condition>
  <condition>Depressive Disorder</condition>
  <condition>Depressive Disorder, Major</condition>
  <condition>Depression, Bipolar</condition>
  <condition>Depressive Episode</condition>
  <arm_group>
    <arm_group_label>Pharmacogenetic Test Guided</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treating physician for this group receives a detailed pharmacogenetic report for the patient, prioritizing 53 psychoactive medications into 4 use categories: preferential use, use as directed, may have significant limitations, and may have severe adverse reactions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment As Usual</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Treating physician receives a sham report listing the names of all drugs and treats patients according to standard of care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Mental Health DNA Insight Test (Pathway Genomics)</intervention_name>
    <description>Pharmacogenetic report based on the patients DNA profile at ~45 SNP markers covering 16 genes</description>
    <arm_group_label>Pharmacogenetic Test Guided</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Sham Test</intervention_name>
    <description>Names of 53 medications listed with &quot;use as directed&quot;</description>
    <arm_group_label>Treatment As Usual</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18&#xD;
&#xD;
          -  Veteran&#xD;
&#xD;
          -  Psychiatric diagnosis&#xD;
&#xD;
          -  Clinically significant depressive symptoms&#xD;
&#xD;
          -  Failed 1 or more adequate treatment trials&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No clinically significant symptoms of depression&#xD;
&#xD;
          -  No previous medication trials&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Inpatient medical or psychiatric hospitalization&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>VA San Diego Healthcare System</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>San Diego Veterans Healthcare System</investigator_affiliation>
    <investigator_full_name>Michael McCarthy</investigator_full_name>
    <investigator_title>Staff Psychiatrist</investigator_title>
  </responsible_party>
  <keyword>pharmacogenetic</keyword>
  <keyword>pharmacogenomic</keyword>
  <keyword>genetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
    <mesh_term>Bipolar Disorder</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/NCT04469322
org study id: H130471
nct id: NCT04469322
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Many patients with depression do not respond well to medication and are diagnosed with
      treatment refractory depression (TRD). Sometimes medications don't work because an individual
      metabolizes the drugs in an atypical manner (too fast/slow). Alternatively, drugs may fail to
      work because the underlying sub-type of depression is not effectively targeted by a
      medication. This study will use genetic testing of subjects with TRD to personalize the drug
      treatment of depression and guide the patient to a better clinical outcome. In the guided
      group, the clinician will receive a pharmacogenetic report to help individually tailor
      medication selection for TRD patients, potentially allowing the clinician to pick more
      effective medications right away, and when necessary, use drug combinations that are
      well-tolerated and less likely to cause unwanted side effects. The control group will receive
      a sham genetic report and be treated according to typical standards of care. The
      investigators will conduct our study in a "real world" setting, with few restrictions on
      which TRD patients can participate. In this way, the findings may be more likely to reveal
      how useful genetic testing will be when applied more broadly in psychiatry.
Study Design and Methods. The investigators will use prospective methods to assess the
      utility of pharmacogenetic guided treatment (PGT) of TRD. The use of genetic testing for PGT
      subjects, and clinical care guided by the individual's genetic results are the only subject
      activities in this study that represent a departure from standard clinical care. Other
      activities carried out within the context of this study are conducted in accordance with
      accepted clinical practice by a trained and licensed psychiatrist. These include (but are not
      limited to) the use of prescription medications, laboratory testing, vital sign measurements,
      mood scales and diagnostic interviews, electrocardiograms, and imaging studies. Standard
      clinical activities will be conducted at the discretion of the attending psychiatrist,
      determined by the clinical needs of the individual patient. All laboratory testing conducted
      for the purposes of clinical treatment (diagnosis, treatment, and prevention of illness) will
      be conducted at the VA San Diego or VA Palo Alto accredited clinical laboratories. No
      investigational medications or devices will be used in this study.

      Setting: Clinical care will be conducted at the Veterans Affairs San Diego Healthcare System
      and Veterans Affairs Palo Alto Healthcare . Patients with TRD will be recruited from multiple
      sites in the local VA Systems. Clinical care will be provided by a VA psychiatrist.

      Genotyping: After obtaining written consent, patients will give a saliva sample from which
      genomic DNA is prepared using established protocols. DNA samples will be assigned a coded
      subject identification number that will not contain any sensitive personal information. The
      code key will remain at the VASDHS at all times. Samples will be sent to a CLIA certified
      laboratory (Pathway Genomics) for genotyping and analyzed using the commercially available
      Mental Health DNA Insight Test. Unused DNA sent for genotyping will be destroyed. No DNA
      storage outside the VASDHS will be permitted. No other clinically relevant information will
      be uncovered by the genetic testing.

      Randomization & Study Design: Patients will be randomly assigned to one of two groups:
      Pharmacogenetic guided treatment (PGT) and treatment as usual (TAU). All patients will
      provide a saliva sample at the start of their participation 5-7 days before their initial
      clinic appointment: All subjects will be genotyped and analyzed using the Mental Health DNA
      Insight Test. The treating physician for the PGT group will receive the report before the
      first clinic visit. The treating physician for the TAU group will receive a sham report.

      Patients will remain blind into which treatment group they are assigned until completion of
      the study. The study physicians will not be blinded due to the need to review the PGT report.
      However, bias will be reduced by using patient self-reports of their mood using the 16-item
      quick inventory of depressive symptoms self report (QIDS-SR16) scale. All patients will then
      be seen by a study psychiatrist at 4 weeks and 8 weeks follow-up. All patients will complete
      self assessment inventories at each visit. In addition they will assess tolerability using a
      standardized side effect checklist. Overall functional impairment and symptom severity will
      be assessed using the Clinical Global Impressions Scale (CGI). Primary study outcome will be
      the CGI score at the end of the study (8 weeks). A Comprehensive Suicide Risk Assessment will
      be done at study initiation and a clinical suicidality assessment will be conducted at every
      visit according to usual clinical practice.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: randomized, single blind, multi-center, prospective
primary purpose: Treatment
masking: Single (Participant)
masking description: patient blinded to condition
measure: Clinical Global Impression (CGI)
time frame: 8 weeks
description: Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
measure: Clinical Global Impression (CGI)
time frame: 0 weeks
description: Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
measure: Clinical Global Impression (CGI)
time frame: 4 weeks
description: Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
measure: Side Effects Burden
time frame: 0 weeks
description: Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
measure: Side Effects Burden
time frame: 4 weeks
description: Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
measure: Side Effects Burden
time frame: 8 weeks
description: Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
measure: Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
time frame: 0 weeks
description: Self Reported Depression Symptoms (scored 1 mild - 27 severe)
measure: Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
time frame: 4 weeks
description: Self Reported Depression Symptoms (scored 1 mild - 27 severe)
measure: Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
time frame: 8 weeks
description: Self Reported Depression Symptoms (scored 1 mild - 27 severe)
arm group label: Pharmacogenetic Test Guided
arm group type: Experimental
description: Treating physician for this group receives a detailed pharmacogenetic report for the patient, prioritizing 53 psychoactive medications into 4 use categories: preferential use, use as directed, may have significant limitations, and may have severe adverse reactions.
arm group label: Treatment As Usual
arm group type: Sham Comparator
description: Treating physician receives a sham report listing the names of all drugs and treats patients according to standard of care.
intervention type: Diagnostic Test
intervention name: Mental Health DNA Insight Test (Pathway Genomics)
description: Pharmacogenetic report based on the patients DNA profile at ~45 SNP markers covering 16 genes
arm group label: Pharmacogenetic Test Guided
intervention type: Diagnostic Test
intervention name: Sham Test
description: Names of 53 medications listed with "use as directed"
arm group label: Treatment As Usual
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: San Diego Veterans Healthcare System
investigator full name: Michael McCarthy
investigator title: Staff Psychiatrist
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Bipolar Disorder
sharing ipd: No