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A Depression and Opioid Pragmatic Trial in Pharmacogenetics (DCRI Coordinating Center) (ADOPT PGx)

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ClinicalTrials.gov Identifier: NCT04445792
Recruitment Status : Recruiting
First Posted : June 24, 2020
Last Update Posted : April 29, 2021
Sponsor:
Information provided by (Responsible Party):
Duke University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Depression Acute Pain Chronic Pain Other: Pharmacogenetic testing Other: Clinical decisions support Not Applicable

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4509 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Depression and Opioid Pragmatic Trial in Pharmacogenetics
Actual Study Start Date : February 10, 2021
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : February 28, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Pain

Arm Intervention/treatment
Experimental: Acute Pain - Immediate PGx Testing
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider
Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19

Other: Clinical decisions support
Prescribing recommendations to the provider based on the pharmacogenetic testing results

Acute Pain - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period
Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19

Experimental: Chronic Pain - Immediate PGx Testing
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider
Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19

Other: Clinical decisions support
Prescribing recommendations to the provider based on the pharmacogenetic testing results

Chronic Pain - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period
Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19

Experimental: Depression - Immediate PGx Testing
Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider
Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19

Other: Clinical decisions support
Prescribing recommendations to the provider based on the pharmacogenetic testing results

Depression - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19




Primary Outcome Measures :
  1. Acute Pain - 10 Day SIA Score Change from Baseline [ Time Frame: Day of Surgery to 10 days post surgery ]
    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.

  2. Chronic Pain -3 Month Pain Control Change from Baseline [ Time Frame: Baseline to 3 months ]
    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

  3. Depression - 3 Month Depression Symptom Control Change from Baseline [ Time Frame: Baseline and 3 months ]
    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


Secondary Outcome Measures :
  1. Acute Pain -10 Day Pain Intensity Change from Baseline [ Time Frame: 10 days post-surgery ]
    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.

  2. Acute Pain Trial - Post-surgery Opioid Usage Change from Baseline [ Time Frame: day of surgery through 10 days post-surgery ]
    Opioid usage from surgery to10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.

  3. Acute Pain Trial - 3 Month Prescription Pain Medication Misuse Change from Baseline [ Time Frame: 3 months post surgery ]
    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.

  4. Acute Pain - 1 Month Mobility Score Change from Baseline [ Time Frame: 1 month post surgery ]
    PROMIS mobility score at 1 month post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.

  5. Acute Pain - Opioid Persistence Change from Baseline [ Time Frame: 3-6 months post-surgery ]
    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

  6. Chromic Pain - 3 Month Pain Reduction Change from Baseline [ Time Frame: baseline and 3 months ]
    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.

  7. Chronic Pain - 3 Month Clinically Significant Pain Reduction Change from Baseline [ Time Frame: 3 months ]
    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

  8. Chronic Pain -3 Month Prescription Pain Medication Misuse Change from Baseline [ Time Frame: 3 months ]
    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

  9. Depression - 3 Month Change in Quick Inventory of Depression Symptomatology (QIDS) Change from Baseline Scores [ Time Frame: baseline and 3 months ]
    Change in QIDS 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

  10. Depression - 3 Month Medication Side Effect Burden Change from Baseline [ Time Frame: 3 months ]
    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

  11. Depression - 3 Month Medication Adherence Change from Baseline [ Time Frame: 3 months ]
    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

  12. Depression - 6 Month Depression Remission Change from Baseline [ Time Frame: 6 months ]
    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.

  13. All Trials Overall well-being, as measured by PROMIS 43 survey [ Time Frame: At 6 month follow-up ]
    Overall well-being

  14. All Trials Concordance between metabolizer phenotype and prescribed medication [ Time Frame: At 6 month follow-up ]
    Concordance between metabolizer phenotype and prescribed medication

  15. 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) ]
    The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do

  16. 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) ]
    The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do

  17. 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) ]
    The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do

  18. 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) ]
    The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do

  19. 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) ]
    The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do

  20. 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) ]
    The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do

  21. 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) ]
    The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Acute Pain

  • Age ≥ 8 years (pediatrics), as this is the minimum age at which proposed outcome measures (PROMIS) are validated without parent proxy
  • English speaking or Spanish speaking
  • Elective/planned surgery patients with an upcoming pre-surgery visit
  • Elective/planned surgery types with pain management, which may include orthopedic surgeries (e.g. arthroplasty, spine, etc.), open abdominal surgery, or cardiothoracic surgery and others

Chronic Pain

  • Age ≥ 18 years
  • English speaking or Spanish speaking
  • Seen at primary care clinics (such as, but not limited to, Internal Medicine, Family Medicine or Pediatrics) or patients seen in relevant specialty clinics
  • Under the care of a physician for pain for at least 3 months and currently or being considered to be treated with tramadol, hydrocodone, or codeine to improve pain management

    • Pain diagnosis
    • Underlying conditions with chronic pain if a pain diagnosis does not exist (not a comprehensive list): arthritis, neuropathy, fibromyalgia, headache.
    • Have a current or planned pain prescription: tramadol, hydrocodone, or codeine

Depression

  • Age ≥ 8 years, as this is the minimum age at which proposed outcome measures (PROMIS) are validated without parent proxy
  • English speaking or Spanish speaking
  • Patients seen at primary care clinics (such as, but not limited to, Internal Medicine, Family Medicine, or Pediatrics) or in psychiatry clinics
  • Diagnosis of depression, defined as problem list entry or ICD-10 diagnosis code with at least 3 months of symptoms
  • Anticipate need for revised or new SSRI therapy for depression

Exclusion Criteria

Trial-wide:

  • Life expectancy less than 12 months
  • Are too cognitively impaired to provide informed consent and/or complete study protocol
  • Are institutionalized or too ill to participate (i.e. mental or nursing home facility)
  • Plan to move out of the area within 6 months of enrollment
  • Have a history of allogeneic stem cell transplant or liver transplant
  • People with prior clinical pharmacogenetic test results for genes relevant for the study in which they will enroll (CYP2D6 for the pain studies and CYP2D6 or CYP2C19 for depression) or already enrolled in an ADOPT PGx trial

Acute Pain

  • Adults with a similar, previous surgery in whom pain control is well-defined and a genotype-guided approach would not likely be followed
  • Undergoing a laparoscopic surgery
  • Receiving chronic opioid therapy, defined as use of opioids on most days for >3 months

Chronic Pain

● Undergoing treatment for an active cancer diagnosis

Depression

  • Have active psychosis or diagnosed psychotic disorders (schizophrenia, schizoaffective disorder, delusional disorder, psychotic depression, substance induced psychosis, schizophreniform disorder)

    • ICD10: F06.2, F20.x, F25.x, F22, F20.81
    • Or a problem list entry indicating the diagnosis of one of these disorders
  • Have dementia or other neurocognitive disorders (due to any cause, such as Alzheimer's disease, vascular/subcortical, lewy body, frontotemporal lobar degeneration)

    • ICD10: F01, F03.x, G31.83, G30.x, G31.09
    • Or a problem list entry indicating the diagnosis of one of these disorders
  • Have cognitive developmental delay and/or cognitive disability, including autism spectrum disorders (Note: this list does not include ADHD)

    • ICD10: F80.x, F81.x, F82.x, F83.x, F84.x, F85.x, F88.x, F89.x
    • Or a problem list entry indicating the diagnosis of one of these disorders
  • Have seizures, or who are on a neuroleptic medication

    • ICD10: G40.x, G41.x
    • Medications: aripiprazole, asenapine, cariprazine, clozapine, lurasidone, olanzapine, quetiapine, risperidone
    • Or a problem list entry indicating the diagnosis of one of these disorders
  • Have bipolar disorder

    • IDC10: F31.x
    • Or a problem list entry indicating the diagnosis of one of these disorders
  • Depression secondary to substance abuse disorder or general medical condition

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04445792


Contacts
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Contact: Teji Rakhra-Burris 919=684-9849 teji.rb@duke.edu

Locations
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United States, Delaware
Nemours/Alfred I. du Pont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Contact: Kathryn Blake, MD    904-697-3600 ext 3806    Kathryn.Blake@nemours.org   
Principal Investigator: Kathryn Blake, MD         
United States, Florida
University of Florida (Gainesville and Jacksonville) Recruiting
Gainesville, Florida, United States, 32610
Contact: Larisa Cavallari, MD    352-273-8245    lcavallari@cop.ufl.edu   
Principal Investigator: Larisa Cavallari, MD         
Nemours Children's Health System Recruiting
Jacksonville, Florida, United States, 32207
Contact: Kathryn Blake, PharmD    904-697-3600 ext 3806    kathryn.blake@nemours.org   
Principal Investigator: Kathryn Blake, PharmD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Todd Skaar, MD    317-460-9748    tskaar@iu.edu   
Principal Investigator: Todd Skaar, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Not yet recruiting
New York, New York, United States, 10029
Contact: Carol Horowitz, MD    212-659-9567    carol.horowitz@mountsinai.org   
Principal Investigator: Carol Horowitz, MD         
The Institute for Family Health Not yet recruiting
New York, New York, United States, 10035
Contact: Neil Calman, MD    212-633-0800 ext 1255    ncalman@institute.org   
Principal Investigator: Neil Calman, MD         
United States, North Carolina
Duke University Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Lori Orlanda, MD    919-660-6606    orlan002@duke.edu   
Principal Investigator: Lori Orlando, MD         
United States, North Dakota
Sanford Health Not yet recruiting
Fargo, North Dakota, United States, 58104
Contact: Lindsey Hines, MD    701-234-4036    Lindsay.Hines@SanfordHealth.org   
Principal Investigator: Lindsey Hines, MD         
United States, Tennessee
Meharry Medical College Not yet recruiting
Nashville, Tennessee, United States, 37208
Contact: Rajbir Singh, MD    615-327-6204    rsingh@mmc.edu   
Principal Investigator: Rajbir Singh, MD         
Vanderbilt University Medical Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Josh Peterson, MD    615-875-1404    josh.peterson@vumc.org   
Principal Investigator: Josh Peterson, MD         
Sponsors and Collaborators
Duke University
Investigators
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Principal Investigator: Hrishikesh Chakraborty Duke University
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT04445792    
Other Study ID Numbers: PRO00104948
First Posted: June 24, 2020    Key Record Dates
Last Update Posted: April 29, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Duke University:
Pharmacogenetic
CYP2D6
CYP2C19
Additional relevant MeSH terms:
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Chronic Pain
Acute Pain
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Pain
Neurologic Manifestations