Implementing Genomics in Practice (IGNITE) Proof of Concept Study: Genotyping in Family Medicine Clinics (IGNITE)

This study will examine the effect of having genotype information on pain management and pain control for patients treated in family medicine clinics. This study will also examine physician-perceived usefulness of genotype information. Patients will be enrolled from family medicine clinics serving as either implementation sites or control sites. Patients from implementation sites will undergo genotyping, while those from control sites will not by genotyped.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Other: Pain assessment questionnaire; Genetic: CYP2D6 genotyping; Other: Physician assessment

Detailed Description

Codeine and tramadol are opioid analgesics that depend on cytochrome P450 2D6 (CYP2D6) for bioactivation to morphine and O-desmethyltramadol, respectively. Morphine and O-desmethyltramadol have much greater affinity for the opioid receptor and thus are more powerful analgesics.

Individuals with genotypes associated with low CYP2D6 activity (poor metabolizers) are unable to convert sufficient amounts of codeine or tramadol to their active metabolites and may fail to derive sufficient pain relief. At the opposite extreme, individuals with genotypes associated with increased CYP2D6 activity (ultra-rapid metabolizers) are at risk for serious toxicity with usual codeine or tramadol doses.

The CYP2D6 genotype also has implications for response to other drugs, such as tricyclic antidepressants (TCAs), which are commonly used for neuropathic pain.

Patients will be recruited from family medicine clinics, serving as either implementation sites or control sites. Patients from implementation sites will undergo CYP2D6 genotyping, with results placed in the medical record to assist with prescribing of pain medications. Pain medications prescribed from baseline to 3 months will be assessed through medical record review. A pain assessment questionnaire will be administered to patients enrolled from both sites at baseline and 3 months.

At the end of the study, a 20-item survey will be administered to physicians at the implementation sites. We will assess whether having CYP2D6 genotype results is useful to inform prescribing decisions for pain medication from the physician's perspective.

We will also assess medicines prescribed to patients enrolled from both sites over the 12-month period after enrollment from medical record review and determine the number of patients who were prescribed a medication that has genetic information in its FDA-approved label.

• Study Type: Observational
• Enrollment (Actual): 505

Contacts and Locations

Study Locations

• United States
  • Florida
    • Archer, Florida, United States, 32618
      • Archer Family Health Care
    • Gainesville, Florida, United States, 32606
      • UF Health Spring Hill Pain Management
    • Gainesville, Florida, United States, 32607
      • UF Health Family Medicine: Hampton Oaks
    • Gainesville, Florida, United States, 32607
      • UF Health Internal Medicine - Tower Hill
    • Gainesville, Florida, United States, 32608
      • UF Health Family Medicine: Haile Plantation
    • Gainesville, Florida, United States, 32609'
      • UF Health Family Medicine: Main Street
    • Gainesville, Florida, United States, 32610
      • UF Health Internal Medicine-Medical Plaza
    • Gainesville, Florida, United States, 32641
      • UF Health Family Medicine: Eastside
    • Old Town, Florida, United States, 32680
      • UF Health Family Medicine - Old Town
    • Oviedo, Florida, United States, 32765
      • Oviedo Family Health Center
    • Saint Cloud, Florida, United States, 34769
      • ProHealth Family Physicians

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients will be enrolled from family medicine clinics serving as either implementation sites or control sites for pain mangement.

Description

Inclusion Criteria:

• Treated in family medicine clinic
• History of pain for at least 3 months
• Prescribed medication for pain relief

Exclusion Criteria:

• Pain for less than 3 months
• Not currently prescribed any medication for pain

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; Patients will continue to receive their current pain management therapy. In addition, a pain assessment questionnaire will be administered at baseline and 3 months.	Other: Pain assessment questionnaire; A pain assessment questionnaire will be administered at baseline and 3 months.; Other Names: PROMIS questionnaire
Implementation; Patients will undergo CYP2D6 genotyping, with results entered into the medical record to assist the physician with prescribing pain medication. In addition, a pain assessment questionnaire will be administered at baseline and 3 months.	Other: Pain assessment questionnaire; A pain assessment questionnaire will be administered at baseline and 3 months.; Other Names: PROMIS questionnaire; Genetic: CYP2D6 genotyping; CYP2D6 genotype results and an interpretive report will be placed in the electronic medical record to assist the physician with prescribing medication for pain management.
Physician assessment; At the end of the study, a 20-item survey will be administered to physicians who treated patients enrolled in the study. The survey will assess whether having CYP2D6 genotype results is useful to inform prescribing decisions for pain medication from the physician's perspective.	Other: Physician assessment; 20-item survey administered to physicians treating patients enrolled in the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in overall pain score (Patient Reported Outcomes Measurement Information System (PROMIS)	Patient Reported Outcomes Measurement Information System (PROMIS) measures will be used to assess pain intensity, physical functioning, and emotional functioning. There are 10 subscales on the PROMIS questionnaire that address the domains of pain, pain functioning, and emotional functioning. At least 4 (and up to 30) items are used to derive a score for each subscale. A computer adaptive version of the questionnaire based on item response theory will be used to administer the survey. A score of 0 to 100 based on survey responses will be resulted for each subscale.	Change from baseline to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain medication	Change in pain medication will be evaluated in several manners: change in the opiate prescribed, change from an opiate to a non-opiate; and change in dose of the opiate prescribed	Change from baseline to 3 months
Change in pain score of pain intensity (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)	Patient Reported Outcomes Measurement Information System (PROMIS) subscale for pain intensity, with the score ranging from 0 to 100 resulting.	Change from baseline to 3 months
Change in pain score of physical functioning (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)	Patient Reported Outcomes Measurement Information System (PROMIS) subscales for physical functioning include pain function, pain interference, pain behavior, sleep disturbance, and sleep-related impairment. A score of 0 to 100 based on survey responses will be resulted for each subscale.	Change from baseline to 3 months
Change in pain score of emotional functioning	Patient Reported Outcomes Measurement Information System (PROMIS) subscales for emotional functioning include fatigue, anxiety, depression, and anger. A score of 0 to 100 based on survey responses will be resulted for each subscale.	Change from baseline to 3 months
Physician perceived usefulness of genetic information (survey)	Survey will be administered to physicians with patients in the study to assess the effect of having genotype information on their prescribing decisions.	3 months
Medications prescribed with pharmacogenetic implications (Percent of patients with at least one other drug (besides an opioid) where genotype information might be useful for prescribing)	Percent of patients with at least one other drug (besides an opioid) where genotype information might be useful for prescribing	12 months

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Human Genome Research Institute (NHGRI)
• Investigators: Principal Investigator: Larisa Cavallari, PharmD, University of Florida

Publications and helpful links

General Publications

• Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE, Caudle KE, Haidar CE, Shen DD, Callaghan JT, Sadhasivam S, Prows CA, Kharasch ED, Skaar TC; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014 Apr;95(4):376-82. doi: 10.1038/clpt.2013.254. Epub 2014 Jan 23.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): June 12, 2017
• Study Completion (Actual): October 25, 2017

Study Registration Dates

• First Submitted: January 7, 2015
• First Submitted That Met QC Criteria: January 8, 2015
• First Posted (Estimate): January 9, 2015

Study Record Updates

• Last Update Posted (Actual): June 6, 2019
• Last Update Submitted That Met QC Criteria: June 5, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Pain; CYP2D6
• Other Study ID Numbers: IRB201400501 - N; U01HG007269-02 (U.S. NIH Grant/Contract); OCR14741 (Other Identifier: Universiy of Florida)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The consent form has an addendum for NIH dbGaP. Participants who agree will have their deidentified results shared to dbGaP. Those who do not agree will not have their results shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No