<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/NCT04445792</url>
  </required_header>
  <id_info>
    <org_study_id>PRO00104948</org_study_id>
    <nct_id>NCT04445792</nct_id>
  </id_info>
  <brief_title>A Depression and Opioid Pragmatic Trial in Pharmacogenetics (DCRI Coordinating Center)</brief_title>
  <acronym>ADOPT PGx</acronym>
  <official_title>A Depression and Opioid Pragmatic Trial in Pharmacogenetics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</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 is comprised of three separate pharmacogenetic trials grouped into a single&#xD;
      protocol due to similarities in the intervention, the hypotheses, and the trial design. The&#xD;
      three trials are the Acute Pain Trial, the Chronic Pain Trial, and the Depression Trial.&#xD;
      Participants can enroll in only one of the three trials.&#xD;
&#xD;
      Acute Pain Trial: A prospective, multicenter, two arm randomized pragmatic trial.&#xD;
      Participants meeting eligibility criteria will be randomly assigned to either immediate&#xD;
      pharmacogenetic testing and genotype-guided post-surgical opioid therapy (Intervention arm)&#xD;
      or standard care and pharmacogenetic testing after 6 months (Control arm). The investigators&#xD;
      will test the hypothesis that pharmacogenetic testing and genotype guided pain management&#xD;
      therapy improves pain control after surgery in participants who's body processes some pain&#xD;
      medicines slower than normal.&#xD;
&#xD;
      Chronic Pain Trial: A prospective, multicenter, two arm randomized pragmatic trial.&#xD;
      Participants meeting eligibility criteria will be randomly assigned to either immediate&#xD;
      pharmacogenetic testing and genotype-guided opioid therapy (Intervention arm) or standard&#xD;
      care with 6-month delayed pharmacogenetic testing (Control arm). The investigators will test&#xD;
      the hypothesis that pharmacogenetic testing and genotype guided pain therapy improves pain&#xD;
      control after surgery in participants who's body processes some pain medicines slower than&#xD;
      normal.&#xD;
&#xD;
      Depression: A prospective, multicenter, two arm randomized pragmatic trial. Participants&#xD;
      meeting eligibility criteria will be randomly assigned to either immediate pharmacogenetic&#xD;
      testing and genotype-guided anti-depressant therapy (Intervention arm) or standard care with&#xD;
      6-month delayed pharmacogenetic testing (Control arm). The investigators will test the&#xD;
      hypothesis that pharmacogenetic testing and genotype-guided anti-depressant therapy will&#xD;
      reduce depression symptoms in participants who's body processes some anti-depressants faster&#xD;
      or slower than normal.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pain and depression are conditions that impact substantial proportions of the US population.&#xD;
      Finding safe and effective drug therapies for both conditions is challenging. In the case of&#xD;
      treatment for acute and chronic pain, the challenge is finding effective therapy while&#xD;
      minimizing adverse effects or opioid addiction (and the ensuing consequences). For&#xD;
      depression, there are few clinically relevant predictors of successful treatment leading to&#xD;
      multiple trials of inadequate therapy for some patients. Both opioid and antidepressant&#xD;
      prescriptions can be guided by pharmacogenetics (PGx) data based on existing guidelines from&#xD;
      the Clinical Pharmacogenetics Implementation Consortium (CPIC).&#xD;
&#xD;
      This study is designed to evaluate the impact of pharmacogenetic testing and genotype-guided&#xD;
      pain or anti-depressant therapy on pain control or depression symptoms in a pragmatic&#xD;
      setting.&#xD;
&#xD;
      The rationale for examining a genotype-guided approach to acute and chronic pain management&#xD;
      is based on the importance of CYP2D6 for the bioactivation of tramadol, codeine, and&#xD;
      hydrocodone and data from a pilot study supporting improved pain control in intermediate and&#xD;
      poor CYP2D6 metabolizers in the genotype-guided arm who are taking these drugs at baseline.&#xD;
      Similarly, the rationale for examining a genotype-guided approach to depression medication&#xD;
      therapy is based on the demonstrated role of CYP2D6 in the bio inactivation and CYP2C19&#xD;
      oxidation of select, commonly used SSRIs. Secondly, data from industry sponsored trials&#xD;
      support the hypothesis of improved depression symptom control in a genotype-guided arm.&#xD;
&#xD;
      Study objectives:&#xD;
&#xD;
      Acute Pain Trial: Determine if a genotype-guided approach to acute post-surgical pain therapy&#xD;
      leads to improved pain control compared to usual care, as defined by a decrease in the SIA&#xD;
      score. Secondarily, The investigators will evaluate whether this approach leads to reduced&#xD;
      use of DEA Schedule II opioids and reduced pain intensity.&#xD;
&#xD;
      Chronic Pain Trial: Determine if a genotype-guided approach to pain therapy in participants&#xD;
      with at least 3 months of chronic pain leads to improved pain control compared to usual care.&#xD;
&#xD;
      Depression Trial: Determine if genotype-guided dosing or selection of antidepressants among&#xD;
      participants with at least 3 months of depressive symptoms who require new or revised&#xD;
      antidepressant therapy leads to improved control of depression, compared to usual care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 10, 2021</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2024</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>Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute Pain - 10 Day SIA Score Change from Baseline</measure>
    <time_frame>Day of Surgery to 10 days post surgery</time_frame>
    <description>Acute Pain: A composite measure of pain and opioid usage, the Silverman Integrated Analgesic Assessment (SIA) score, at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chronic Pain -3 Month Pain Control Change from Baseline</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>Chronic Pain: Pain control, defined as change in the composite pain intensity score from baseline to 3-months in participants who have genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. The composite pain intensity score is derived from the PROMIS pain intensity scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Depression - 3 Month Depression Symptom Control Change from Baseline</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>Depression symptom control, defined as change in PROMIS depression T-scores from baseline to 3-months in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute Pain -10 Day Pain Intensity Change from Baseline</measure>
    <time_frame>10 days post-surgery</time_frame>
    <description>PROMIS Numeric Pain Rating Scale Pain intensity at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Pain Trial - Post-surgery Opioid Usage Change from Baseline</measure>
    <time_frame>day of surgery through 10 days post-surgery</time_frame>
    <description>Opioid usage from surgery to10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Pain Trial - 3 Month Prescription Pain Medication Misuse Change from Baseline</measure>
    <time_frame>3 months post surgery</time_frame>
    <description>PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Pain - 1 Month Mobility Score Change from Baseline</measure>
    <time_frame>1 month post surgery</time_frame>
    <description>PROMIS mobility score at 1 month post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Pain - Opioid Persistence Change from Baseline</measure>
    <time_frame>3-6 months post-surgery</time_frame>
    <description>Opioid persistence defined as a filled prescription for an opioid medication 3-6 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic Pain - 3 Month Pain Reduction Change from Baseline</measure>
    <time_frame>baseline and 3 months</time_frame>
    <description>Pain reduction is defined as the ratio of the 3 month and baseline composite pain scores in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic Pain - 3 Month Clinically Significant Pain Reduction Change from Baseline</measure>
    <time_frame>3 months</time_frame>
    <description>PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic Pain -3 Month Prescription Pain Medication Misuse Change from Baseline</measure>
    <time_frame>3 months</time_frame>
    <description>PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression - 3 Month Change in PHQ of Depression Symptomatology Change from Baseline Scores</measure>
    <time_frame>baseline and 3 months</time_frame>
    <description>Change in PHQ-8 scores between baseline and 3 months in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers. Achieve 50% reduction in scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression - 3 Month Medication Side Effect Burden Change from Baseline</measure>
    <time_frame>3 months</time_frame>
    <description>Side effect burden is defined as the number of side effects experienced from a specified list of possible side effects, weighted by the severity of each side effect in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression - 3 Month Medication Adherence Change from Baseline</measure>
    <time_frame>3 months</time_frame>
    <description>Medication adherence score derived from the Voils Medication Adherence survey in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression - 6 Month Depression Remission Change from Baseline</measure>
    <time_frame>6 months</time_frame>
    <description>Remission is defined as whether or not the summed raw responses to the PROMIS emotional distress depression survey is ≤ 16, corresponding to a participant respond &quot;rarely&quot; or &quot;never&quot; to most or all questions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Overall well-being, as measured by PROMIS 43 survey</measure>
    <time_frame>At 6 month follow-up</time_frame>
    <description>Overall well-being</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Concordance between metabolizer phenotype and prescribed medication</measure>
    <time_frame>At 6 month follow-up</time_frame>
    <description>Concordance between metabolizer phenotype and prescribed medication</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Sub-domain of the PROMIS 43 survey: Pain interference</measure>
    <time_frame>At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)</time_frame>
    <description>The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Sub-domain of the PROMIS 43 survey: physical function</measure>
    <time_frame>At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)</time_frame>
    <description>The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Sub-domain of the PROMIS 43 survey: sleep disturbance</measure>
    <time_frame>At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)</time_frame>
    <description>The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Sub-domain of the PROMIS 43 survey: social role and activities functioning</measure>
    <time_frame>At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)</time_frame>
    <description>The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Sub-domain of the PROMIS 43 survey: fatigue</measure>
    <time_frame>At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)</time_frame>
    <description>The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Sub-domain of the PROMIS 43 survey: anxiety</measure>
    <time_frame>At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)</time_frame>
    <description>The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Trials Sub-domain of the PROMIS 43 survey: depression</measure>
    <time_frame>At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)</time_frame>
    <description>The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">4509</enrollment>
  <condition>Depression</condition>
  <condition>Acute Pain</condition>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Acute Pain - Immediate PGx Testing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acute Pain - Delayed PGx Testing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chronic Pain - Immediate PGx Testing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chronic Pain - Delayed PGx Testing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Depression - Immediate PGx Testing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Depression - Delayed PGx Testing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacogenetic testing</intervention_name>
    <description>Genetic testing of CYP2D6 and CYP2C19</description>
    <arm_group_label>Acute Pain - Delayed PGx Testing</arm_group_label>
    <arm_group_label>Acute Pain - Immediate PGx Testing</arm_group_label>
    <arm_group_label>Chronic Pain - Delayed PGx Testing</arm_group_label>
    <arm_group_label>Chronic Pain - Immediate PGx Testing</arm_group_label>
    <arm_group_label>Depression - Delayed PGx Testing</arm_group_label>
    <arm_group_label>Depression - Immediate PGx Testing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical decisions support</intervention_name>
    <description>Prescribing recommendations to the provider based on the pharmacogenetic testing results</description>
    <arm_group_label>Acute Pain - Immediate PGx Testing</arm_group_label>
    <arm_group_label>Chronic Pain - Immediate PGx Testing</arm_group_label>
    <arm_group_label>Depression - Immediate PGx Testing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Acute Pain&#xD;
&#xD;
          -  Age ≥ 8 years&#xD;
&#xD;
          -  English speaking or Spanish speaking&#xD;
&#xD;
          -  Elective/planned surgery types with planned or anticipated to be treated with&#xD;
             tramadol, hydrocodone, or codeine pain management at an enrolling site, which may&#xD;
             include orthopedic surgeries (e.g. arthroplasty, spine, etc.), open abdominal surgery,&#xD;
             or cardiothoracic surgery and others&#xD;
&#xD;
        Chronic Pain&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  English speaking or Spanish speaking&#xD;
&#xD;
          -  Seen at primary care clinics (such as, but not limited to, Internal Medicine, Family&#xD;
             Medicine or Pediatrics) or patients seen in pain-relevant specialty clinics&#xD;
&#xD;
          -  History of pain for at least the last 3 months&#xD;
&#xD;
          -  Currently treated or being considered for treatment with tramadol, hydrocodone, or&#xD;
             codeine to improve pain management&#xD;
&#xD;
        Depression&#xD;
&#xD;
          -  Age ≥ 8 years&#xD;
&#xD;
          -  English speaking or Spanish speaking&#xD;
&#xD;
          -  Patients followed at psychiatry clinics or primary care clinics at an enrolling site&#xD;
             (such as, but not limited to, Internal Medicine, Family Medicine, or Pediatrics)&#xD;
&#xD;
          -  Documentation of depression and/or provider report of depression&#xD;
&#xD;
          -  Evidence of depressive symptoms for at least 3 months based on patient interview or&#xD;
             documentation in electronic health records&#xD;
&#xD;
          -  Recent initiation of SSRI therapy, recent revised SSRI therapy, or anticipated need&#xD;
             for revised or new SSRI therapy per health care provider&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Trial-wide:&#xD;
&#xD;
          -  Life expectancy less than 12 months&#xD;
&#xD;
          -  Are too cognitively impaired to provide informed consent and/or complete study&#xD;
             protocol&#xD;
&#xD;
          -  Are institutionalized or too ill to participate (i.e. mental or nursing home facility&#xD;
             or incarcerated)&#xD;
&#xD;
          -  Have a history of allogeneic stem cell transplant or liver transplant&#xD;
&#xD;
          -  People with prior clinical pharmacogenetic test results for genes relevant for the&#xD;
             study in which they will enroll (CYP2D6 for the pain studies and CYP2D6 or CYP2C19 for&#xD;
             depression) or already enrolled in an ADOPT PGx trial&#xD;
&#xD;
        Acute Pain&#xD;
&#xD;
          -  Undergoing a laparoscopic surgery&#xD;
&#xD;
          -  Receiving chronic opioid therapy, defined as use of opioids on most days for &gt;3 months&#xD;
&#xD;
        Chronic Pain&#xD;
&#xD;
          -  Plan to move out of the area within 6 months of enrollment&#xD;
&#xD;
          -  Undergoing treatment for an active cancer diagnosis&#xD;
&#xD;
          -  Currently taking daily opioids other than tramadol, codeine or hydrocodone&#xD;
&#xD;
        Depression&#xD;
&#xD;
          -  Plan to move out of the area within 6 months of enrollment&#xD;
&#xD;
          -  Have active psychosis or diagnosed psychotic disorders (schizophrenia, schizoaffective&#xD;
             disorder, delusional disorder, psychotic depression, substance induced psychosis,&#xD;
             schizophreniform disorder)&#xD;
&#xD;
          -  Have dementia or other neurocognitive disorders due to any cause, such as Alzheimer's&#xD;
             disease, vascular/subcortical, lewy body disease, frontotemporal lobar degeneration&#xD;
&#xD;
          -  Have cognitive developmental delay and/or cognitive disability, including autism&#xD;
             spectrum disorders (Note: ADHD is not an exclusion criteria)&#xD;
&#xD;
          -  Has a seizure disorder&#xD;
&#xD;
          -  Have bipolar disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hrishikesh Chakraborty</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kady-Ann Steen-Burrell</last_name>
    <phone>919-530-9711</phone>
    <email>kady.ann.steen.burrell@duke.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Nemours Children's Health System</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19803</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathryn Blake, PharmD</last_name>
      <phone>904-697-3600</phone>
      <phone_ext>3806</phone_ext>
      <email>kathryn.blake@nemours.org</email>
    </contact>
    <investigator>
      <last_name>Kathryn Blake, Pharm D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Florida - Gainesville</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Larisa Cavallari, MD</last_name>
      <phone>352-273-8245</phone>
      <email>lcavallari@cop.ufl.edu</email>
    </contact>
    <investigator>
      <last_name>Larisa Cavallari, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Health System</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathryn Blake, PharmD</last_name>
      <phone>904-697-3600</phone>
      <phone_ext>3806</phone_ext>
      <email>kathryn.blake@nemours.org</email>
    </contact>
    <investigator>
      <last_name>Kathryn Blake, PharmD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Florida - Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Larisa Cavallari, MD</last_name>
      <phone>352-273-8245</phone>
      <email>lcavallari@cop.ufl.edu</email>
    </contact>
    <investigator>
      <last_name>Larisa Cavallari, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Health System</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32827</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathryn Blake, PharmD</last_name>
      <phone>904-697-3600</phone>
      <phone_ext>3806</phone_ext>
      <email>kathryn.blake@nemours.org</email>
    </contact>
    <investigator>
      <last_name>Kathryn Blake, PharmD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Eskenazi Health</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Todd Skaar, MD</last_name>
      <phone>317-460-9748</phone>
      <email>tskaar@iu.edu</email>
    </contact>
    <investigator>
      <last_name>Todd Skaar, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Todd Skaar, MD</last_name>
      <phone>317-460-9748</phone>
      <email>tskaar@iu.edu</email>
    </contact>
    <investigator>
      <last_name>Todd Skaar, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carol Horowitz, MD</last_name>
      <phone>212-659-9567</phone>
      <email>carol.horowitz@mountsinai.org</email>
    </contact>
    <investigator>
      <last_name>Carol Horowitz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Institute for Family Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10035</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Neil Calman, MD</last_name>
      <phone>212-633-0800</phone>
      <phone_ext>1255</phone_ext>
      <email>ncalman@institute.org</email>
    </contact>
    <investigator>
      <last_name>Neil Calman, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Deepak Voora, MD</last_name>
      <phone>919-684-6266</phone>
      <email>deepak.voora@duke.edu</email>
    </contact>
    <investigator>
      <last_name>Deepak Voora, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sanford Health</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lindsey Hines, MD</last_name>
      <phone>701-234-4036</phone>
      <email>Lindsay.Hines@SanfordHealth.org</email>
    </contact>
    <investigator>
      <last_name>Lindsey Hines, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Meharry Medical College</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37208</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rajbir Singh, MD</last_name>
      <phone>615-327-6204</phone>
      <email>rsingh@mmc.edu</email>
    </contact>
    <investigator>
      <last_name>Rajbir Singh, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nashville General Hospital</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37208</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rajbir Singh, MD</last_name>
      <phone>615-327-6204</phone>
      <email>rsingh@mmc.edu</email>
    </contact>
    <investigator>
      <last_name>Rajbir Singh, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Josh Peterson, MD</last_name>
      <phone>615-875-1404</phone>
      <email>josh.peterson@vumc.org</email>
    </contact>
    <investigator>
      <last_name>Josh Peterson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>July 7, 2023</last_update_submitted>
  <last_update_submitted_qc>July 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacogenetic</keyword>
  <keyword>CYP2D6</keyword>
  <keyword>CYP2C19</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chronic Pain</mesh_term>
    <mesh_term>Acute Pain</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive 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/NCT04445792
org study id: PRO00104948
nct id: NCT04445792
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is comprised of three separate pharmacogenetic trials grouped into a single
      protocol due to similarities in the intervention, the hypotheses, and the trial design. The
      three trials are the Acute Pain Trial, the Chronic Pain Trial, and the Depression Trial.
      Participants can enroll in only one of the three trials.

      Acute Pain Trial: A prospective, multicenter, two arm randomized pragmatic trial.
      Participants meeting eligibility criteria will be randomly assigned to either immediate
      pharmacogenetic testing and genotype-guided post-surgical opioid therapy (Intervention arm)
      or standard care and pharmacogenetic testing after 6 months (Control arm). The investigators
      will test the hypothesis that pharmacogenetic testing and genotype guided pain management
      therapy improves pain control after surgery in participants who's body processes some pain
      medicines slower than normal.

      Chronic Pain Trial: A prospective, multicenter, two arm randomized pragmatic trial.
      Participants meeting eligibility criteria will be randomly assigned to either immediate
      pharmacogenetic testing and genotype-guided opioid therapy (Intervention arm) or standard
      care with 6-month delayed pharmacogenetic testing (Control arm). The investigators will test
      the hypothesis that pharmacogenetic testing and genotype guided pain therapy improves pain
      control after surgery in participants who's body processes some pain medicines slower than
      normal.

      Depression: A prospective, multicenter, two arm randomized pragmatic trial. Participants
      meeting eligibility criteria will be randomly assigned to either immediate pharmacogenetic
      testing and genotype-guided anti-depressant therapy (Intervention arm) or standard care with
      6-month delayed pharmacogenetic testing (Control arm). The investigators will test the
      hypothesis that pharmacogenetic testing and genotype-guided anti-depressant therapy will
      reduce depression symptoms in participants who's body processes some anti-depressants faster
      or slower than normal.
Pain and depression are conditions that impact substantial proportions of the US population.
      Finding safe and effective drug therapies for both conditions is challenging. In the case of
      treatment for acute and chronic pain, the challenge is finding effective therapy while
      minimizing adverse effects or opioid addiction (and the ensuing consequences). For
      depression, there are few clinically relevant predictors of successful treatment leading to
      multiple trials of inadequate therapy for some patients. Both opioid and antidepressant
      prescriptions can be guided by pharmacogenetics (PGx) data based on existing guidelines from
      the Clinical Pharmacogenetics Implementation Consortium (CPIC).

      This study is designed to evaluate the impact of pharmacogenetic testing and genotype-guided
      pain or anti-depressant therapy on pain control or depression symptoms in a pragmatic
      setting.

      The rationale for examining a genotype-guided approach to acute and chronic pain management
      is based on the importance of CYP2D6 for the bioactivation of tramadol, codeine, and
      hydrocodone and data from a pilot study supporting improved pain control in intermediate and
      poor CYP2D6 metabolizers in the genotype-guided arm who are taking these drugs at baseline.
      Similarly, the rationale for examining a genotype-guided approach to depression medication
      therapy is based on the demonstrated role of CYP2D6 in the bio inactivation and CYP2C19
      oxidation of select, commonly used SSRIs. Secondly, data from industry sponsored trials
      support the hypothesis of improved depression symptom control in a genotype-guided arm.

      Study objectives:

      Acute Pain Trial: Determine if a genotype-guided approach to acute post-surgical pain therapy
      leads to improved pain control compared to usual care, as defined by a decrease in the SIA
      score. Secondarily, The investigators will evaluate whether this approach leads to reduced
      use of DEA Schedule II opioids and reduced pain intensity.

      Chronic Pain Trial: Determine if a genotype-guided approach to pain therapy in participants
      with at least 3 months of chronic pain leads to improved pain control compared to usual care.

      Depression Trial: Determine if genotype-guided dosing or selection of antidepressants among
      participants with at least 3 months of depressive symptoms who require new or revised
      antidepressant therapy leads to improved control of depression, compared to usual care.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy
primary purpose: Treatment
masking: None (Open Label)
measure: Acute Pain - 10 Day SIA Score Change from Baseline
time frame: Day of Surgery to 10 days post surgery
description: Acute Pain: A composite measure of pain and opioid usage, the Silverman Integrated Analgesic Assessment (SIA) score, at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.
measure: Chronic Pain -3 Month Pain Control Change from Baseline
time frame: Baseline to 3 months
description: Chronic Pain: Pain control, defined as change in the composite pain intensity score from baseline to 3-months in participants who have genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. The composite pain intensity score is derived from the PROMIS pain intensity scale
measure: Depression - 3 Month Depression Symptom Control Change from Baseline
time frame: Baseline and 3 months
description: Depression symptom control, defined as change in PROMIS depression T-scores from baseline to 3-months in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers
measure: Acute Pain -10 Day Pain Intensity Change from Baseline
time frame: 10 days post-surgery
description: PROMIS Numeric Pain Rating Scale Pain intensity at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.
measure: Acute Pain Trial - Post-surgery Opioid Usage Change from Baseline
time frame: day of surgery through 10 days post-surgery
description: Opioid usage from surgery to10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.
measure: Acute Pain Trial - 3 Month Prescription Pain Medication Misuse Change from Baseline
time frame: 3 months post surgery
description: PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.
measure: Acute Pain - 1 Month Mobility Score Change from Baseline
time frame: 1 month post surgery
description: PROMIS mobility score at 1 month post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.
measure: Acute Pain - Opioid Persistence Change from Baseline
time frame: 3-6 months post-surgery
description: Opioid persistence defined as a filled prescription for an opioid medication 3-6 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75
measure: Chronic Pain - 3 Month Pain Reduction Change from Baseline
time frame: baseline and 3 months
description: Pain reduction is defined as the ratio of the 3 month and baseline composite pain scores in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.
measure: Chronic Pain - 3 Month Clinically Significant Pain Reduction Change from Baseline
time frame: 3 months
description: PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75
measure: Chronic Pain -3 Month Prescription Pain Medication Misuse Change from Baseline
time frame: 3 months
description: PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75
measure: Depression - 3 Month Change in PHQ of Depression Symptomatology Change from Baseline Scores
time frame: baseline and 3 months
description: Change in PHQ-8 scores between baseline and 3 months in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers. Achieve 50% reduction in scores.
measure: Depression - 3 Month Medication Side Effect Burden Change from Baseline
time frame: 3 months
description: Side effect burden is defined as the number of side effects experienced from a specified list of possible side effects, weighted by the severity of each side effect in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers
measure: Depression - 3 Month Medication Adherence Change from Baseline
time frame: 3 months
description: Medication adherence score derived from the Voils Medication Adherence survey in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers
measure: Depression - 6 Month Depression Remission Change from Baseline
time frame: 6 months
description: Remission is defined as whether or not the summed raw responses to the PROMIS emotional distress depression survey is ≤ 16, corresponding to a participant respond "rarely" or "never" to most or all questions.
measure: All Trials Overall well-being, as measured by PROMIS 43 survey
time frame: At 6 month follow-up
description: Overall well-being
measure: All Trials Concordance between metabolizer phenotype and prescribed medication
time frame: At 6 month follow-up
description: Concordance between metabolizer phenotype and prescribed medication
measure: All Trials Sub-domain of the PROMIS 43 survey: Pain interference
time frame: At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
description: The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do
measure: All Trials Sub-domain of the PROMIS 43 survey: physical function
time frame: At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
description: The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do
measure: All Trials Sub-domain of the PROMIS 43 survey: sleep disturbance
time frame: At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
description: The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do
measure: All Trials Sub-domain of the PROMIS 43 survey: social role and activities functioning
time frame: At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
description: The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do
measure: All Trials Sub-domain of the PROMIS 43 survey: fatigue
time frame: At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
description: The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do
measure: All Trials Sub-domain of the PROMIS 43 survey: anxiety
time frame: At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
description: The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do
measure: All Trials Sub-domain of the PROMIS 43 survey: depression
time frame: At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
description: The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do
arm group label: Acute Pain - Immediate PGx Testing
arm group type: Experimental
description: Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider
arm group label: Acute Pain - Delayed PGx Testing
arm group type: Other
description: Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period
arm group label: Chronic Pain - Immediate PGx Testing
arm group type: Experimental
description: Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider
arm group label: Chronic Pain - Delayed PGx Testing
arm group type: Other
description: Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period
arm group label: Depression - Immediate PGx Testing
arm group type: Experimental
description: Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider
arm group label: Depression - Delayed PGx Testing
arm group type: Other
description: Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
intervention type: Other
intervention name: Pharmacogenetic testing
description: Genetic testing of CYP2D6 and CYP2C19
arm group label: Acute Pain - Delayed PGx Testing
arm group label: Acute Pain - Immediate PGx Testing
arm group label: Chronic Pain - Delayed PGx Testing
arm group label: Chronic Pain - Immediate PGx Testing
arm group label: Depression - Delayed PGx Testing
arm group label: Depression - Immediate PGx Testing
intervention type: Other
intervention name: Clinical decisions support
description: Prescribing recommendations to the provider based on the pharmacogenetic testing results
arm group label: Acute Pain - Immediate PGx Testing
arm group label: Chronic Pain - Immediate PGx Testing
arm group label: Depression - Immediate PGx Testing
criteria: 
gender: All
minimum age: 8 Years
maximum age: N/A
healthy volunteers: No
last name: Hrishikesh Chakraborty
role: Principal Investigator
affiliation: Duke University
last name: Kady-Ann Steen-Burrell
phone: 919-530-9711
email: kady.ann.steen.burrell@duke.edu
facility: 
status: Recruiting
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country: United States
responsible party type: Sponsor
mesh term: Chronic Pain
mesh term: Acute Pain
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: No