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| ID | Type | Description | Link |
|---|---|---|---|
| U01HG010225 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Human Genome Research Institute (NHGRI) | NIH |
| University of Florida | OTHER |
| Vanderbilt University Medical Center | OTHER |
| Indiana University |
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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. All three trials were registered on ClinicalTrials.gov under NCT04445792. In July 2023 each of the three treatment trials was registered under a separate NCT# and NCT04445792 was converted to a screening record per recent guidance on master protocol research programs (MPRPs). This record is specific to the Chronic Pain Trial within the ADOPT-PGx protocol.
The Chronic Pain Trial is 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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronic Pain - Immediate PGx Testing | Experimental | Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider |
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| Chronic Pain - Delayed PGx Testing | Other | Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pharmacogenetic testing | Other | Genetic testing of CYP2D6 and CYP2C19 |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Pain Intensity | The composite pain intensity score is derived from the 3-time PROMIS (Patient-Reported Outcomes Measurement Information System) pain intensity scale. Composite pain intensity score is the sum of the 3 questions and ranges from 3 (no pain) to 15 (intense pain). Change in composite pain intensity score ranges from -12 (change from the highest level of pain to the lowest level of pain) to 12 (change from the lowest level of pain to the highest level of pain). | Baseline to 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Pain Reduction Magnitude | Ratio of Composite Pain Score at 3 months relative to baseline. Composite pain intensity scores were shifted to range 0-12 and the pain reduction magnitude is reported as the ratio of pain at 3 months relative to pain at baseline using this adjusted scale. Statistical analyses were conducted using the log ratio pain at 3 months relative to pain at baseline. Due to the presence of 0 values in the ratios, the log ratios include a +.5 offset, i.e. log(3-month pain +.5 / baseline pain + 0.5). |
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Inclusion Criteria:
Chronic Pain Trial
Exclusion Criteria
Trial-wide:
Chronic Pain
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| Name | Affiliation | Role |
|---|---|---|
| Hrishikesh Chakraborty | Duke University | Study Director |
| Todd Skaar, PhD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida - Gainesville | Gainesville | Florida | 32610 | United States | ||
| University of Florida - Jacksonville |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39177194 | Background | Skaar TC, Myers RA, Fillingim RB, Callaghan JT, Cicali E, Eadon MT, Elwood EN, Ginsburg GS, Lynch S, Nguyen KA, Obeng AO, Park H, Pratt VM, Rosenman M, Sadeghpour A, Shuman S, Singh R, Tillman EM, Volpi S, Wiisanen K, Winterstein AG, Horowitz CR, Voora D, Orlando L, Chakraborty H, Van Driest S, Peterson JF, Cavallari LA, Johnson JA, Dexter PR; IGNITE Pragmatic Trials Network. Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators. Clin Transl Sci. 2024 Aug;17(8):e70005. doi: 10.1111/cts.70005. |
| Label | URL |
|---|---|
| Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators | View source |
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There were 1092 participants consented into the Chronic Pain trial. Of the 1092, 44 were not randomized into the trial and were not assigned to a treatment arm. The remaining 1048 consented participants were randomized and assigned into the treatment arms. The 1048 randomized participants will be described moving forward.
This record is specific to the Chronic Pain Trial within the ADOPT PGx protocol. It only contains the participants consented to the Chronic Pain Trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | Chronic Pain - Immediate PGx Testing | Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider. |
| FG001 | Chronic Pain - Delayed PGx Testing |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 23, 2024 |
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| OTHER |
| Icahn School of Medicine at Mount Sinai | OTHER |
Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy
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| Clinical decisions support | Other | Prescribing recommendations to the provider based on the pharmacogenetic testing results |
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| Baseline to 3 months |
| Number of Participants With Clinically Significant Pain Reduction | Clinically significant pain reduction defined as ratio of 3-month composite pain score relative to baseline is < 0.7, corresponding to a 30% or more improvement in pain scores. | Baseline to 3 months |
| Prescription Pain Medication Misuse as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System) | The 7-item PROMIS questionnaire assesses the extent to which participant experience prescription pain medication misuse symptoms in the past 3 months using a 5-point Likert scale. Participants are asked if they have had a prescription for pain medication in the last 3 months. If no, the questionnaire is not administered, if yes, the questionnaire is administered. For the completed questionnaires. Raw scores ranging from 7 to 35. Raw scores are converted to T-scores using the PROMIS conversion table, with T-scores ranging 36.3 to 54.1. Higher T-scores reflect greater symptom severity. | 3 months |
| Number of Participants With Drug-Gene Concordance | Concordance between the participant reported opioid medications at 3 months and CYP2D6 phenotype. | 3 months |
| Jacksonville |
| Florida |
| 32209 |
| United States |
| Eskenazi Health | Indianapolis | Indiana | 46202 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| The Institute for Family Health | New York | New York | 10035 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Meharry Medical College | Nashville | Tennessee | 37208 | United States |
| Nashville General Hospital | Nashville | Tennessee | 37208 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period.
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| NOT COMPLETED |
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ITT refers to the Intent To Treat population, while mITT, a subset of ITT, refers to the modified Intent To Treat population. The mITT population is the primary analytical population for the Chronic Pain Trial and includes participants who have a CYP2D6 activity scores <= 0.75 after accounting for CYP2D6 phenoconversion.
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| ID | Title | Description |
|---|---|---|
| BG000 | Chronic Pain - Immediate PGx Testing | Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider. |
| BG001 | Chronic Pain - Delayed PGx Testing | Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Intent to Treat (ITT) population | Mean | Standard Deviation | years |
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| Age, Continuous | Modified Intent to Treat (mITT) population | Mean | Standard Deviation | years |
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| Sex: Female, Male | Intent to Treat (ITT) population. Three participants declined to answer. | Count of Participants | Participants |
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| Sex: Female, Male | Modified Intent to Treat (mITT) population. Two participants declined to answer. | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Intent to Treat (ITT) population | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Modified Intent to Treat (mITT) population | Count of Participants | Participants |
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| Race (NIH/OMB) | Intent to Treat (ITT) population | Count of Participants | Participants |
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| Race (NIH/OMB) | Modified Intent to Treat (mITT) population | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Pain Intensity | The composite pain intensity score is derived from the 3-time PROMIS (Patient-Reported Outcomes Measurement Information System) pain intensity scale. Composite pain intensity score is the sum of the 3 questions and ranges from 3 (no pain) to 15 (intense pain). Change in composite pain intensity score ranges from -12 (change from the highest level of pain to the lowest level of pain) to 12 (change from the lowest level of pain to the highest level of pain). | Modified Intent to Treat (mITT) population with completed baseline and 3-month pain surveys. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 3 months |
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| Secondary | Pain Reduction Magnitude | Ratio of Composite Pain Score at 3 months relative to baseline. Composite pain intensity scores were shifted to range 0-12 and the pain reduction magnitude is reported as the ratio of pain at 3 months relative to pain at baseline using this adjusted scale. Statistical analyses were conducted using the log ratio pain at 3 months relative to pain at baseline. Due to the presence of 0 values in the ratios, the log ratios include a +.5 offset, i.e. log(3-month pain +.5 / baseline pain + 0.5). | Modified Intent to Treat (mITT) population with completed baseline and 3-month pain surveys. | Posted | Mean | Standard Deviation | log ratio | Baseline to 3 months |
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| Secondary | Number of Participants With Clinically Significant Pain Reduction | Clinically significant pain reduction defined as ratio of 3-month composite pain score relative to baseline is < 0.7, corresponding to a 30% or more improvement in pain scores. | Modified Intent to Treat (mITT) population with completed baseline and 3-month pain surveys. | Posted | Count of Participants | Participants | Baseline to 3 months |
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| Secondary | Prescription Pain Medication Misuse as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System) | The 7-item PROMIS questionnaire assesses the extent to which participant experience prescription pain medication misuse symptoms in the past 3 months using a 5-point Likert scale. Participants are asked if they have had a prescription for pain medication in the last 3 months. If no, the questionnaire is not administered, if yes, the questionnaire is administered. For the completed questionnaires. Raw scores ranging from 7 to 35. Raw scores are converted to T-scores using the PROMIS conversion table, with T-scores ranging 36.3 to 54.1. Higher T-scores reflect greater symptom severity. | Modified Intent to Treat (mITT) participants who indicate having taken a prescription for pain medication in the past 3 months. | Posted | Mean | Standard Deviation | T-score | 3 months |
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| Secondary | Number of Participants With Drug-Gene Concordance | Concordance between the participant reported opioid medications at 3 months and CYP2D6 phenotype. | Modified Intent to Treat (mITT) participants with prescription pain medication data collected. | Posted | Count of Participants | Participants | 3 months |
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Up to 6 months
Per the study protocol, only Adverse Device Effect (ADE) events suspected to be related to the specimen collection, laboratory assay genotyping results, and phenoconversion recommendations from the Best Practice Alerts (BPAs)/Consult notes were reported to the IRB. Reportable ADEs or unanticipated Adverse Device Effect (UADEs) events including unanticipated study related deaths will be collected in the study database per IRB reporting policies. Medication side effects were not included as AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chronic Pain - Immediate PGx Testing | Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider. | 3 | 527 | 0 | 527 | 0 | 527 |
| EG001 | Chronic Pain - Delayed PGx Testing | Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period. | 3 | 521 | 0 | 521 | 0 | 521 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hrishikesh Chakraborty, PhD | Duke University | 919-668-1238 | hrishikesh.chakraborty@duke.edu |
| May 9, 2025 |
| Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 14, 2023 | Nov 14, 2023 | ICF_000.pdf |
| ID | Term |
|---|---|
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000071185 | Pharmacogenomic Testing |
| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |
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