- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04445792
A Depression and Opioid Pragmatic Trial in Pharmacogenetics (DCRI Coordinating Center) (ADOPT PGx)
A Depression and Opioid Pragmatic Trial in Pharmacogenetics
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.
Each trial is listed individually on clinicaltrials.gov and includes "PRO00104948" within the Unique Protocol ID:
PRO00104948_A - Acute Pain Trial - NCT05966129
PRO00104948_B - Chronic Pain Trial - NCT05966142
PRO00104948_C - Depression Trial - NCT05966155
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Delaware
-
Wilmington, Delaware, United States, 19803
- Nemours Children's Health System
-
-
Florida
-
Gainesville, Florida, United States, 32610
- University of Florida - Gainesville
-
Jacksonville, Florida, United States, 32209
- University of Florida - Jacksonville
-
Jacksonville, Florida, United States, 32207
- Nemours Children's Health System
-
Orlando, Florida, United States, 32827
- Nemours Children's Health System
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University
-
Indianapolis, Indiana, United States, 46202
- Eskenazi Health
-
-
New York
-
New York, New York, United States, 10029
- Icahn School of Medicine at Mount Sinai
-
New York, New York, United States, 10035
- The Institute for Family Health
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
-
North Dakota
-
Fargo, North Dakota, United States, 58104
- Sanford Health
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
-
Nashville, Tennessee, United States, 37208
- Meharry Medical College
-
Nashville, Tennessee, United States, 37208
- Nashville General Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
|
Genetic testing of CYP2D6 and CYP2C19
Prescribing recommendations to the provider based on the pharmacogenetic testing results
|
Other: Acute Pain - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period
|
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
|
Genetic testing of CYP2D6 and CYP2C19
Prescribing recommendations to the provider based on the pharmacogenetic testing results
|
Other: Chronic Pain - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period
|
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
|
Genetic testing of CYP2D6 and CYP2C19
Prescribing recommendations to the provider based on the pharmacogenetic testing results
|
Other: 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
|
Genetic testing of CYP2D6 and CYP2C19
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Day of Surgery to 10 days post surgery
|
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
|
Baseline to 3 months
|
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
|
Baseline and 3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
10 days post-surgery
|
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.
|
day of surgery through 10 days post-surgery
|
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.
|
3 months post surgery
|
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.
|
1 month post surgery
|
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
|
3-6 months post-surgery
|
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.
|
baseline and 3 months
|
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
|
3 months
|
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
|
3 months
|
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.
|
baseline and 3 months
|
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
|
3 months
|
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
|
3 months
|
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.
|
6 months
|
All Trials Overall well-being, as measured by PROMIS 43 survey
Time Frame: At 6 month follow-up
|
Overall well-being
|
At 6 month follow-up
|
All Trials Concordance between metabolizer phenotype and prescribed medication
Time Frame: At 6 month follow-up
|
Concordance between metabolizer phenotype and prescribed medication
|
At 6 month follow-up
|
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
|
At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
|
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
|
At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
|
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
|
At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
|
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
|
At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
|
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
|
At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
|
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
|
At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
|
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
|
At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hrishikesh Chakraborty, Duke University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRO00104948
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Depression
-
ProgenaBiomeRecruitingDepression | Depression, Postpartum | Depression, Anxiety | Depression Moderate | Depression Severe | Clinical Depression | Depression in Remission | Depression, Endogenous | Depression ChronicUnited States
-
Washington University School of MedicineCompletedTreatment Resistant Depression | Late Life Depression | Geriatric Depression | Refractory Depression | Therapy-Resistant DepressionUnited States, Canada
-
Kintsugi Mindful Wellness, Inc.Sonar Strategies; Vituity PsychiatryRecruitingDepression | Depression Moderate | Depression Severe | Depression MildUnited States
-
University of California, San FranciscoRecruitingDepression Moderate | Depression Mild | Depression, TeenUnited States
-
University GhentUniversiteit Antwerpen; Janssen-Cilag Ltd.RecruitingDepression Moderate | Depression Severe | Depression MildBelgium
-
Baylor College of MedicineUniversity of TexasRecruitingDepression | Depression Moderate | Depression Severe | Suicide and Self-harm | Depression in Adolescence | Depression MildUnited States
-
University of Cape TownNational Institute of Mental Health (NIMH)CompletedPostpartum Depression | Clinical Depression | Moderate DepressionSouth Africa
-
Washington University School of MedicinePatient-Centered Outcomes Research Institute; National Institute of Mental...CompletedMajor Depressive Disorder | Treatment Resistant Depression | Treatment-Refractory Depression | Late Life Depression | Geriatric DepressionUnited States, Canada
-
Northern Illinois UniversityUniversity Autonoma de Santo DomingoTerminatedDepression Moderate | Depression MildUnited States, Dominican Republic
-
Gerbera Therapeutics, Inc.Not yet recruitingPostpartum Depression | Depression, Postpartum | Postnatal Depression | Post-partum Depression | Post-Natal DepressionUnited States
Clinical Trials on Pharmacogenetic testing
-
University of CalgaryRecruiting
-
Avera McKennan Hospital & University Health CenterCompletedDepressionUnited States
-
Maastricht University Medical CenterKing's College London; State University of New York - Upstate Medical University and other collaboratorsRecruitingPsychotic Disorders | Mood Disorders | Anxiety DisordersUnited States, Germany, Netherlands, Spain, Serbia, Romania, United Kingdom
-
Duke UniversityNational Institute of General Medical Sciences (NIGMS)Completed
-
University of ArizonaUnknownDepression | Obsessive-Compulsive Disorder | Generalized Anxiety Disorder
-
Avera McKennan Hospital & University Health CenterCompletedEvaluation of Pharmacogenetic Testing In a Mental Health Population and Economic Outcomes (PGx-TIME)Major Depressive Disorder 1United States
-
Anna VlasovaRussian Medical Academy of Continuous Professional Education; Morozov Children...CompletedDrug TherapyRussian Federation
-
Medstar Health Research InstituteKailos Genetics, Inc.Active, not recruitingChronic PainUnited States
-
Cairo UniversityAin Shams University; Misr International UniversityUnknown
-
Avera McKennan Hospital & University Health CenterCompletedMajor Depressive DisorderUnited States