Clinical trial NCT05966142: A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Chronic Pain Trial)
Official title: A Depression and Opioid Pragmatic Trial in Pharmacogenetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Pain
Keywords: Pharmacogenetic
CYP2D6
CYP2C19
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
name: University of Florida
name: Vanderbilt University Medical Center
name: Indiana University School of Medicine
name: Icahn School of Medicine at Mount Sinai
First posted: 2023-07-28
Enrollment: 1048
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Pain Intensity
timeFrame: Baseline to 3 months
Secondary outcomes:
measure: Pain Reduction Magnitude
timeFrame: Baseline to 3 months
measure: Number of Participants With Clinically Significant Pain Reduction
timeFrame: Baseline to 3 months
measure: Prescription Pain Medication Misuse as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 3 months
measure: Number of Participants With Drug-Gene Concordance
timeFrame: 3 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: University of Florida - Jacksonville
state: Florida
city: Indianapolis
country: United States
facility: Eskenazi Health
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: The Institute for Family Health
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Nashville
country: United States
facility: Nashville General Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Duke University
name: Hrishikesh Chakraborty
role: STUDY_DIRECTOR
affiliation: Indiana University
name: Todd Skaar, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.