Clinical trial NCT04445792: A Depression and Opioid Pragmatic Trial in Pharmacogenetics (DCRI Coordinating Center)
Official title: A Depression and Opioid Pragmatic Trial in Pharmacogenetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Acute Pain
Chronic Pain
Keywords: Pharmacogenetic
CYP2D6
CYP2C19
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2020-06-24
Enrollment: 4284
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 is a Master Protocol Screening record. 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Individuals Identified as Potential Participants Through EHR (Electronic Health Record)
timeFrame: Up to 3 years
measure: Number of Individuals Who Were Screened to the Acute Pain, Chronic Pain, and Depression Trials
timeFrame: Up to 3 years
measure: Number of Participants Who Were Randomized to the Acute Pain, Chronic Pain, and Depression Trials
timeFrame: Up to 3 years
Secondary outcomes:
measure: Pain Interference as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 6 months
measure: Physical Function as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 6 months
measure: Sleep Disturbance as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 6 months
measure: Ability to Participant in Social Roles and Activities as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 6 months
measure: Fatigue as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 6 months
measure: Anxiety as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 6 months
measure: Depression as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 6 months
measure: Overall Wellbeing as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)
timeFrame: 6 months
measure: Number of Participants With Pharmacogenetic Drug-Gene Concordance
timeFrame: 10 days for Acute Pain; 3 months for Chronic Pain and Depression
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: Jacksonville
country: United States
facility: University of Florida - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Health System
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: 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: 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.
citation: Hines LJ, Wilke RA, Myers R, Mathews CA, Liu M, Baye JF, Petry N, Cicali EJ, Duong BQ, Elwood E, Hulvershorn L, Nguyen K, Ramos M, Sadeghpour A, Wu RR, Williamson L, Wiisanen K, Voora D, Singh R, Blake KV, Murrough JW, Volpi S, Ginsburg GS, Horowitz CR, Orlando L, Chakraborty H, Dexter P, Johnson JA, Skaar TC, Cavallari LH, Van Driest SL, Peterson JF; IGNITE Pragmatic Trials Network. Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression. Clin Transl Sci. 2024 Jun;17(6):e13822. doi: 10.1111/cts.13822.
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.