A Depression and Opioid Pragmatic Trial in Pharmacogenetics (DCRI Coordinating Center)

Depression Clinical Trial

— ADOPT PGx  

Official title:

A Depression and Opioid Pragmatic Trial in Pharmacogenetics

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04445792
• Other study ID #: PRO00104948
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 10, 2021
• Est. completion date: August 1, 2024

Study information

• Verified date: July 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4111
• Est. completion date: August 1, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Pain
• Chronic Pain
• Depression
• Depressive Disorder

Intervention

Other:
• Pharmacogenetic testing
Genetic testing of CYP2D6 and CYP2C19
• Clinical decisions support
Prescribing recommendations to the provider based on the pharmacogenetic testing results

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina
United States	Sanford Health	Fargo	North Dakota
United States	University of Florida - Gainesville	Gainesville	Florida
United States	Eskenazi Health	Indianapolis	Indiana
United States	Indiana University	Indianapolis	Indiana
United States	Nemours Children's Health System	Jacksonville	Florida
United States	University of Florida - Jacksonville	Jacksonville	Florida
United States	Meharry Medical College	Nashville	Tennessee
United States	Nashville General Hospital	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
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	Nemours Children's Health System	Orlando	Florida
United States	Nemours Children's Health System	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Pain - 10 Day SIA Score Change from Baseline	Acute Pain: A composite measure of pain and opioid usage, the Silverman Integrated Analgesic Assessment (SIA) score, at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75.	Day of Surgery to 10 days post surgery
Primary	Chronic Pain -3 Month Pain Control Change from Baseline	Chronic Pain: Pain control, defined as change in the composite pain intensity score from baseline to 3-months in participants who have genotypic or pheno-converted CYP2D6 activity score = 0.75. The composite pain intensity score is derived from the PROMIS pain intensity scale	Baseline to 3 months
Primary	Depression - 3 Month Depression Symptom Control Change from Baseline	Depression symptom control, defined as change in PROMIS depression T-scores from baseline to 3-months in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers	Baseline and 3 months
Secondary	Acute Pain -10 Day Pain Intensity Change from Baseline	PROMIS Numeric Pain Rating Scale Pain intensity at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75.	10 days post-surgery
Secondary	Acute Pain Trial - Post-surgery Opioid Usage Change from Baseline	Opioid usage from surgery to10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75.	day of surgery through 10 days post-surgery
Secondary	Acute Pain Trial - 3 Month Prescription Pain Medication Misuse Change from Baseline	PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75.	3 months post surgery
Secondary	Acute Pain - 1 Month Mobility Score Change from Baseline	PROMIS mobility score at 1 month post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75.	1 month post surgery
Secondary	Acute Pain - Opioid Persistence Change from Baseline	Opioid persistence defined as a filled prescription for an opioid medication 3-6 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75	3-6 months post-surgery
Secondary	Chronic Pain - 3 Month Pain Reduction Change from Baseline	Pain reduction is defined as the ratio of the 3 month and baseline composite pain scores in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75.	baseline and 3 months
Secondary	Chronic Pain - 3 Month Clinically Significant Pain Reduction Change from Baseline	PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75	3 months
Secondary	Chronic Pain -3 Month Prescription Pain Medication Misuse Change from Baseline	PROMIS prescription pain medication misuse T-scores at 3 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score = 0.75	3 months
Secondary	Depression - 3 Month Change in PHQ of Depression Symptomatology Change from Baseline Scores	Change in PHQ-8 scores between baseline and 3 months in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers. Achieve 50% reduction in scores.	baseline and 3 months
Secondary	Depression - 3 Month Medication Side Effect Burden Change from Baseline	Side effect burden is defined as the number of side effects experienced from a specified list of possible side effects, weighted by the severity of each side effect in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers	3 months
Secondary	Depression - 3 Month Medication Adherence Change from Baseline	Medication adherence score derived from the Voils Medication Adherence survey in genotypic or pheno-converted CYP2D6 ultra-rapid or poor metabolizers or CYP2C19 ultra-rapid, rapid, or poor metabolizers	3 months
Secondary	Depression - 6 Month Depression Remission Change from Baseline	Remission is defined as whether or not the summed raw responses to the PROMIS emotional distress depression survey is = 16, corresponding to a participant respond "rarely" or "never" to most or all questions.	6 months
Secondary	All Trials Overall well-being, as measured by PROMIS 43 survey	Overall well-being	At 6 month follow-up
Secondary	All Trials Concordance between metabolizer phenotype and prescribed medication	Concordance between metabolizer phenotype and prescribed medication	At 6 month follow-up
Secondary	All Trials Sub-domain of the PROMIS 43 survey: Pain interference	The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do	At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
Secondary	All Trials Sub-domain of the PROMIS 43 survey: physical function	The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do	At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
Secondary	All Trials Sub-domain of the PROMIS 43 survey: sleep disturbance	The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do	At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
Secondary	All Trials Sub-domain of the PROMIS 43 survey: social role and activities functioning	The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do	At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
Secondary	All Trials Sub-domain of the PROMIS 43 survey: fatigue	The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do	At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
Secondary	All Trials Sub-domain of the PROMIS 43 survey: anxiety	The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do	At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)
Secondary	All Trials Sub-domain of the PROMIS 43 survey: depression	The assessment scale options are: without any difficulty, with a little difficulty, with some difficulty, with much difficulty or unable to do	At 6 months post return of results (chronic pain and depression; 6 months post surgery for acute pain)

External Links

•   Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators