<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/NCT02189057</url>
  </required_header>
  <id_info>
    <org_study_id>13-007981</org_study_id>
    <nct_id>NCT02189057</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic/Pharmacodynamic Genetic Variation Treatment Algorithm Versus Treatment As Usual for Management Of Depression</brief_title>
  <acronym>MOD</acronym>
  <official_title>A Pharmacokinetic/Pharmacodynamic Genetic Variation Treatment Algorithm Versus Treatment As Usual for Management of Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</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>
      The overall goal of this investigator-initiated trial is to evaluate the treatment outcome of&#xD;
      depression utilizing platform algorithm products that can allow rapid identification of&#xD;
      pharmacokinetic (PK) and/or pharmacodynamic (PD) genomic variation. This new technology may&#xD;
      have the potential to optimize treatment selection by improving response, minimizing&#xD;
      unfavorable adverse events / side effects and increasing treatment adherence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Treatment seeking depressed patients (SCID confirmed major depressive disorder or bipolar&#xD;
      I/II disorder) to the Mayo Clinic Depression Center will be invited to participate in this&#xD;
      study evaluating the Assurex GeneSight® platform; this new technology can rapidly assess PK&#xD;
      and PD genetic variation that can potentially impact antidepressant, antipsychotic, and&#xD;
      stimulant associated treatment outcomes for depression. This study will recruit treatment&#xD;
      seeking patients with major depression with an index episode of moderate symptom severity&#xD;
      that has been unresponsive or poorly tolerated to at least one prior antidepressant&#xD;
      treatment. This will be an 8-week, double-blind trial where depressed patients are randomized&#xD;
      to testing results of GeneSight® (tricolored clinical report) prior to treatment selection&#xD;
      (n=138) vs. treatment as usual (tricolored dummy report) (n=138). All testing results will be&#xD;
      made available after the 8-week trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2014</start_date>
  <completion_date type="Actual">October 19, 2018</completion_date>
  <primary_completion_date type="Actual">October 19, 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>Crossover Assignment</intervention_model>
    <intervention_model_description>Subjects will be randomized to either genotyping intervention or treatment as usual.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Subject and study staff will be blind to randomization.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in depression as measured by the Quick Inventory of Depressive Symptoms (QIDS-C16)</measure>
    <time_frame>baseline, 8 weeks</time_frame>
    <description>The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores &gt;/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with improvement of depressive symptoms as shown by 50% reduction in QIDS-C16 score</measure>
    <time_frame>8 weeks</time_frame>
    <description>The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores &gt;/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with improvement of depressive symptoms as shown by a score &lt;6 on QIDS-C16</measure>
    <time_frame>8 weeks</time_frame>
    <description>The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores &gt;/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with improvement of depressive symptoms as shown by score of &quot;much&quot; or &quot;very much improved&quot; on Clinical Global Impression - Improvement Scale</measure>
    <time_frame>8 weeks</time_frame>
    <description>The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1. Very much improved, 2. Much improved, 3. Minimally improved, 4. No change, 5. Minimally worse, 6. Much worse, 7. Very much worse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of depressive symptoms as shown by the Hamilton Rating Scale for Depression (HAMD-17)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The HAMD-17 is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items are rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17 score ranges from 0 (not ill) to 52 (severely ill). A negative change indicates improvement in the subject's depression/anxiety symptoms, and a positive change indicates a worsening of the subject's depression/anxiety symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of depressive symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>Treatment adherence based on concordance vs. non-concordance of gene test results and clinical intervention.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Depression</condition>
  <condition>Mood Disorder</condition>
  <condition>Bipolar</condition>
  <arm_group>
    <arm_group_label>GeneSight guided treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GeneSight guided group will have their research psychiatrist make treatment recommendations based on AssureRx GeneSight genotyping results.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment as usual group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment as usual group will have treatment recommendations based on clinical judgment</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>AssureRx GeneSight genotyping results</intervention_name>
    <arm_group_label>GeneSight guided treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Treatment as usual</intervention_name>
    <arm_group_label>Treatment as usual group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-65, male or female, any race/ethnicity&#xD;
&#xD;
          2. Mayo Clinic Depression Center inpatient or outpatient, or an outpatient of Mayo Clinic&#xD;
             Rochester and satellite clinics, and outpatients from Mayo Clinic Health System&#xD;
             clinics&#xD;
&#xD;
          3. Ability to provide informed consent&#xD;
&#xD;
          4. Structured Clinical Interview (SCID) confirmed major depressive episode associated&#xD;
             with Major Depressive Disorder, Bipolar I/II disorder, or Schizoaffective Bipolar&#xD;
             Disorder&#xD;
&#xD;
          5. Current index episode of major depression &lt; 2 years duration&#xD;
&#xD;
          6. Moderate symptom severity defined by HAMD-17 rating scale score ≥ 17 [8]&#xD;
&#xD;
          7. Current index episode having not been treated with psychotropic medications or&#xD;
             inadequately responsive to treatment (IRT). IRT defined as intolerability, adverse&#xD;
             event, or inadequate efficacy of current psychotropic medication (at least 4 weeks&#xD;
             duration)&#xD;
&#xD;
          8. Agree to abide by the study protocol and its restrictions and be able to complete all&#xD;
             aspects of the study, including all visits and tests&#xD;
&#xD;
          9. Negative serum or urine pregnancy test (or history of hysterectomy)&#xD;
&#xD;
         10. Negative urine toxicology test (will only be completed at the request of the treating&#xD;
             clinician).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to speak English&#xD;
&#xD;
          2. Inability or lack of willingness to provide informed consent&#xD;
&#xD;
          3. Axis I or II disorder other than depression (i.e., by clinical assessment) that is the&#xD;
             primary reason for treatment&#xD;
&#xD;
          4. Psychotropic medication change (including dosage) between screening &amp; baseline visit&#xD;
             with exception of no more than 8mg of Ativan within a 24-hour period.&#xD;
&#xD;
          5. Patients who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)&#xD;
             criteria for any significant current substance use disorder other than nicotine or&#xD;
             caffeine. Must have at least early, partial or full, remission X 3 months&#xD;
&#xD;
          6. Clinically diagnosed cannabis use disorder, or SCID confirmed cannabis abuse or&#xD;
             dependence.&#xD;
&#xD;
          7. Current clinical diagnosis delirium, dementia, other cognitive disorders, or non-mood&#xD;
             psychotic disorder (i.e., schizophrenia, delusional disorder)&#xD;
&#xD;
          8. Index episode symptoms of hallucinations or delusions&#xD;
&#xD;
          9. Serious suicidal risk and/or in need of immediate hospitalization as judged by the&#xD;
             investigator&#xD;
&#xD;
         10. History of hypothyroidism unless taking a stable dose of thyroid medication and&#xD;
             asymptomatic for 6 months&#xD;
&#xD;
         11. Significant unstable medical condition&#xD;
&#xD;
         12. Hepatic insufficiency (2.5 X upper limit of normal (ULN) for Aspartate&#xD;
             Aminotransferase (AST) or Alanine Aminotransferase (ALT) ), past liver transplant&#xD;
             recipient, and/or clinical diagnosis of cirrhosis of the liver&#xD;
&#xD;
         13. Malignancy (except basal cell carcinoma) and/or chemotherapy within 1 year prior to&#xD;
             screening; malignancy more than 1 year prior to screening must have been local and&#xD;
             without metastasis and/or recurrence, and if treated with chemotherapy, without&#xD;
             nervous system complications&#xD;
&#xD;
         14. Participation in another clinical trial within 30 days of the screening visit&#xD;
&#xD;
         15. Anticipated inability to attend scheduled study visits&#xD;
&#xD;
         16. Patients who in the judgment of the Investigator may be unreliable or uncooperative&#xD;
             with the evaluation procedure outlined in this protocol&#xD;
&#xD;
         17. Known cytochrome (CYP) &amp; serotonin transporter genomic testing results within 5 years&#xD;
&#xD;
         18. A score of ≥15 on the Young Mania Rating Scale (YMRS)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Frye, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>October 19, 2018</last_update_submitted>
  <last_update_submitted_qc>October 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Mark Frye</investigator_full_name>
    <investigator_title>Chair-Psychiatry/Psychology</investigator_title>
  </responsible_party>
  <keyword>Bipolar</keyword>
  <keyword>Unipolar</keyword>
  <keyword>Genotyping</keyword>
  <keyword>Pharmacokinetic</keyword>
  <keyword>Pharmacodynamic</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>Mood 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/NCT02189057
org study id: 13-007981
nct id: NCT02189057
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The overall goal of this investigator-initiated trial is to evaluate the treatment outcome of
      depression utilizing platform algorithm products that can allow rapid identification of
      pharmacokinetic (PK) and/or pharmacodynamic (PD) genomic variation. This new technology may
      have the potential to optimize treatment selection by improving response, minimizing
      unfavorable adverse events / side effects and increasing treatment adherence.
Treatment seeking depressed patients (SCID confirmed major depressive disorder or bipolar
      I/II disorder) to the Mayo Clinic Depression Center will be invited to participate in this
      study evaluating the Assurex GeneSight® platform; this new technology can rapidly assess PK
      and PD genetic variation that can potentially impact antidepressant, antipsychotic, and
      stimulant associated treatment outcomes for depression. This study will recruit treatment
      seeking patients with major depression with an index episode of moderate symptom severity
      that has been unresponsive or poorly tolerated to at least one prior antidepressant
      treatment. This will be an 8-week, double-blind trial where depressed patients are randomized
      to testing results of GeneSight® (tricolored clinical report) prior to treatment selection
      (n=138) vs. treatment as usual (tricolored dummy report) (n=138). All testing results will be
      made available after the 8-week trial.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Subjects will be randomized to either genotyping intervention or treatment as usual.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Subject and study staff will be blind to randomization.
measure: Change in depression as measured by the Quick Inventory of Depressive Symptoms (QIDS-C16)
time frame: baseline, 8 weeks
description: The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.
measure: Number of subjects with improvement of depressive symptoms as shown by 50% reduction in QIDS-C16 score
time frame: 8 weeks
description: The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.
measure: Number of subjects with improvement of depressive symptoms as shown by a score <6 on QIDS-C16
time frame: 8 weeks
description: The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.
measure: Number of subjects with improvement of depressive symptoms as shown by score of "much" or "very much improved" on Clinical Global Impression - Improvement Scale
time frame: 8 weeks
description: The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1. Very much improved, 2. Much improved, 3. Minimally improved, 4. No change, 5. Minimally worse, 6. Much worse, 7. Very much worse
measure: Improvement of depressive symptoms as shown by the Hamilton Rating Scale for Depression (HAMD-17)
time frame: 8 weeks
description: The HAMD-17 is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items are rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17 score ranges from 0 (not ill) to 52 (severely ill). A negative change indicates improvement in the subject's depression/anxiety symptoms, and a positive change indicates a worsening of the subject's depression/anxiety symptoms.
measure: Improvement of depressive symptoms
time frame: 8 weeks
description: Treatment adherence based on concordance vs. non-concordance of gene test results and clinical intervention.
arm group label: GeneSight guided treatment
arm group type: Experimental
description: GeneSight guided group will have their research psychiatrist make treatment recommendations based on AssureRx GeneSight genotyping results.
arm group label: Treatment as usual group
arm group type: Active Comparator
description: Treatment as usual group will have treatment recommendations based on clinical judgment
intervention type: Other
intervention name: AssureRx GeneSight genotyping results
arm group label: GeneSight guided treatment
intervention type: Other
intervention name: Treatment as usual
arm group label: Treatment as usual group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Mark Frye, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Mark Frye
investigator title: Chair-Psychiatry/Psychology
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Mood Disorders