Clinical trial NCT05966129: A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Acute Pain Trial)
Official title: A Depression and Opioid Pragmatic Trial in Pharmacogenetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute 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: 1602
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
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 Acute Pain Trial within the ADOPT-PGx protocol.

The Acute 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 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.

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 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.

Eligibility criteria: Inclusion Criteria:

Acute Pain Trial

* 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

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 Trial

* Undergoing a laparoscopic surgery
* Receiving chronic opioid therapy, defined as use of opioids on most days for \>3 months

Primary outcomes:
measure: 10 Day Silverman Integrated Analgesic Assessment (SIA) Score
timeFrame: Day of surgery (baseline) to 10 days post surgery
Secondary outcomes:
measure: 10 Day Pain Intensity as Measured by the PROMIS Numeric Pain Rating Scale
timeFrame: 10 days post-surgery
measure: Post-surgery Opioid Usage, Measured in Milligrams of Morphine Equivalents (MME) Per Day
timeFrame: Day of surgery (baseline) to 10 days post surgery
measure: 3 Month Prescription Pain Medication Misuse
timeFrame: 3 months post surgery
measure: 1 Month PROMIS Mobility Score
timeFrame: 1 month post surgery
measure: Number of Participants With Opioid Persistence
timeFrame: 3-6 months post-surgery, assessed at 6 months
measure: Participants With Drug-Gene Concordance
timeFrame: Within 10 days post-surgery
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Nemours Children's Health System
state: Delaware
city: Gainesville
country: United States
facility: University of Florida - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Health System
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Health System
state: Florida
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: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fargo
country: United States
facility: Sanford Health
state: North Dakota
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: University of Florida
name: Larisa H. Cavallari, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Julie A. Johnson, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cavallari LH, Cicali E, Wiisanen K, Fillingim RB, Chakraborty H, Myers RA, Blake KV, Asiyanbola B, Baye JF, Bronson WH, Cook KJ, Elwood EN, Gray CF, Gong Y, Hines L, Kannry J, Kucher N, Lynch S, Nguyen KA, Obeng AO, Pratt VM, Prieto HA, Ramos M, Sadeghpour A, Singh R, Rosenman M, Starostik P, Thomas CD, Tillman E, Dexter PR, Horowitz CR, Orlando LA, Peterson JF, Skaar TC, Van Driest SL, Volpi S, Voora D, Parvataneni HK, Johnson JA; IGNITE Pragmatic Trials Network. Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators. Clin Transl Sci. 2022 Oct;15(10):2479-2492. doi: 10.1111/cts.13376. Epub 2022 Aug 4.