A Depression and Opioid Pragmatic Trial in Pharmacogenetics (DCRI Coordinating Center) (ADOPT PGx)
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| ClinicalTrials.gov Identifier: NCT04445792 |
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Recruitment Status :
Recruiting
First Posted : June 24, 2020
Last Update Posted : February 23, 2023
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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 |
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.
| 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 : | April 30, 2024 |
| Estimated Study Completion Date : | April 30, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Acute Pain - Immediate PGx Testing
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider
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Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19 Other: Clinical decisions support Prescribing recommendations to the provider based on the pharmacogenetic testing results |
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Acute Pain - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period
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Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19 |
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Experimental: Chronic Pain - Immediate PGx Testing
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider
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Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19 Other: Clinical decisions support Prescribing recommendations to the provider based on the pharmacogenetic testing results |
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Chronic Pain - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period
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Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19 |
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Experimental: Depression - Immediate PGx Testing
Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider
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Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19 Other: Clinical decisions support Prescribing recommendations to the provider based on the pharmacogenetic testing results |
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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
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Other: Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19 |
- 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.
- 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
- 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
- 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.
- 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.
- 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.
- 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.
- 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
- Chronic 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.
- 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
- 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
- Depression - 3 Month Change in PHQ of Depression Symptomatology Change from Baseline Scores [ Time Frame: baseline and 3 months ]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.
- 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
- 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
- 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.
- All Trials Overall well-being, as measured by PROMIS 43 survey [ Time Frame: At 6 month follow-up ]Overall well-being
- All Trials Concordance between metabolizer phenotype and prescribed medication [ Time Frame: At 6 month follow-up ]Concordance between metabolizer phenotype and prescribed medication
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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.
| Ages Eligible for Study: | 8 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Acute Pain
- Age ≥ 8 years
- English speaking or Spanish speaking
- Elective/planned surgery types with planned or anticipated to be treated with tramadol, hydrocodone, or codeine pain management at an enrolling site, 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 pain-relevant specialty clinics
- History of pain for at least the last 3 months
- Currently treated or being considered for treatment with tramadol, hydrocodone, or codeine to improve pain management
Depression
- Age ≥ 8 years
- English speaking or Spanish speaking
- Patients followed at psychiatry clinics or primary care clinics at an enrolling site (such as, but not limited to, Internal Medicine, Family Medicine, or Pediatrics)
- Documentation of depression and/or provider report of depression
- Evidence of depressive symptoms for at least 3 months based on patient interview or documentation in electronic health records
- Recent initiation of SSRI therapy, recent revised SSRI therapy, or anticipated need for revised or new SSRI therapy per health care provider
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 or incarcerated)
- 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
- Undergoing a laparoscopic surgery
- Receiving chronic opioid therapy, defined as use of opioids on most days for >3 months
Chronic Pain
- Plan to move out of the area within 6 months of enrollment
- Undergoing treatment for an active cancer diagnosis
- Currently taking daily opioids other than tramadol, codeine or hydrocodone
Depression
- Plan to move out of the area within 6 months of enrollment
- Have active psychosis or diagnosed psychotic disorders (schizophrenia, schizoaffective disorder, delusional disorder, psychotic depression, substance induced psychosis, schizophreniform disorder)
- Have dementia or other neurocognitive disorders due to any cause, such as Alzheimer's disease, vascular/subcortical, lewy body disease, frontotemporal lobar degeneration
- Have cognitive developmental delay and/or cognitive disability, including autism spectrum disorders (Note: ADHD is not an exclusion criteria)
- Has a seizure disorder
- Have bipolar disorder
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
| Contact: Kady-Ann Steen-Burrell | 919-530-9711 | kady.ann.steen.burrell@duke.edu |
| United States, Delaware | |
| Nemours Children's Health System | Recruiting |
| Wilmington, Delaware, United States, 19803 | |
| Contact: Kathryn Blake, PharmD 904-697-3600 ext 3806 kathryn.blake@nemours.org | |
| Principal Investigator: Kathryn Blake, Pharm D | |
| United States, Florida | |
| University of Florida - Gainesville | 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 | |
| University of Florida - Jacksonville | Recruiting |
| Jacksonville, Florida, United States, 32209 | |
| Contact: Larisa Cavallari, MD 352-273-8245 lcavallari@cop.ufl.edu | |
| Principal Investigator: Larisa Cavallari, MD | |
| Nemours Children's Health System | Recruiting |
| Orlando, Florida, United States, 32827 | |
| Contact: Kathryn Blake, PharmD 904-697-3600 ext 3806 kathryn.blake@nemours.org | |
| Principal Investigator: Kathryn Blake, PharmD | |
| United States, Indiana | |
| Eskenazi Health | Recruiting |
| Indianapolis, Indiana, United States, 46202 | |
| Contact: Todd Skaar, MD 317-460-9748 tskaar@iu.edu | |
| Principal Investigator: Todd Skaar, MD | |
| 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 | 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 | 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 Medical Center | Recruiting |
| Durham, North Carolina, United States, 27710 | |
| Contact: Deepak Voora, MD 919-684-6266 deepak.voora@duke.edu | |
| Principal Investigator: Deepak Voora, MD | |
| United States, North Dakota | |
| Sanford Health | 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 | Recruiting |
| Nashville, Tennessee, United States, 37208 | |
| Contact: Rajbir Singh, MD 615-327-6204 rsingh@mmc.edu | |
| Principal Investigator: Rajbir Singh, MD | |
| Nashville General Hospital | 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 | Recruiting |
| Nashville, Tennessee, United States, 37232 | |
| Contact: Josh Peterson, MD 615-875-1404 josh.peterson@vumc.org | |
| Principal Investigator: Josh Peterson, MD | |
| Principal Investigator: | Hrishikesh Chakraborty | Duke University |
| Responsible Party: | Duke University |
| ClinicalTrials.gov Identifier: | NCT04445792 |
| Other Study ID Numbers: |
PRO00104948 |
| First Posted: | June 24, 2020 Key Record Dates |
| Last Update Posted: | February 23, 2023 |
| Last Verified: | August 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Pharmacogenetic CYP2D6 CYP2C19 |
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Chronic Pain Acute Pain Depression Depressive Disorder Behavioral Symptoms |
Mood Disorders Mental Disorders Pain Neurologic Manifestations |