A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Chronic Pain Trial)

Not Applicable

Completed

Conditions: Chronic Pain

Registration Number: NCT05966142

Lead Sponsor: 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. 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.

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:

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1048

Inclusion Criteria

Chronic Pain Trial

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

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

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Pain Intensity	Baseline to 3 months	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).

Secondary Outcome Measures

Name	Time	Method
Pain Reduction Magnitude	Baseline to 3 months	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).
Number of Participants With Clinically Significant Pain Reduction	Baseline to 3 months	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.
Prescription Pain Medication Misuse as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)	3 months	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.
Number of Participants With Drug-Gene Concordance	3 months	Concordance between the participant reported opioid medications at 3 months and CYP2D6 phenotype.

Trial Locations

Locations (10): University of Florida - Gainesville
🇺🇸
Gainesville, Florida, United States
University of Florida - Jacksonville
🇺🇸
Jacksonville, Florida, United States
Eskenazi Health
🇺🇸
Indianapolis, Indiana, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
The Institute for Family Health
🇺🇸
New York, New York, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Meharry Medical College
🇺🇸
Nashville, Tennessee, United States
Nashville General Hospital
🇺🇸
Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
University of Florida - Gainesville
🇺🇸Gainesville, Florida, United States