Pharmacogenetic Testing and Chronic Pain

The Utility of Genetic Testing in Predicting Drug Response in Chronic Pain

Understanding the impact of genetics could aid rational, precision drug choices. In the current study, investigators will focus on whether genetic analysis of drug processing using the Inagene platform could predict efficacy and side effect profile in patients prescribed medication for pain.

Study Overview

• Status: Suspended
• Conditions: Chronic Pain
• Intervention / Treatment: Diagnostic test: Genetic test for drug response prediction

Detailed Description

Understanding the impact of genetics could aid rational, precision drug choices. In the current study, investigators will focus on whether genetic analysis of drug processing using the Inagene platform could predict efficacy and side effect profile in patients prescribed medication for pain. In the investigator's clinic commonly employed medications included nortriptyline, duloxetine, topiramate, gabapentin, pregabalin, opioids (morphine derivatives, tramadol, tapentadol, buprenorphine patch), cesamet (a synthetic cannabinoid). To the investigator's knowledge this type of study has not been completed in this environment and/or patient population.

Research Objectives:

The main goal of this study is to determine whether genetic analysis of drug processing could help predict efficacy and side effect profiles of medications in a cohort of patients suffering from chronic pain.

In order to control for various clinical factors, patient reported outcomes will also be collected. As a standard part of any patient intake, pain diagrams, measures of pain, function, mental health status and exercise describe the conditions and relative impact will be included. Investigators will include various standardized and/or adapted versions of other questionnaires which will allow investigators to control for known confounders.

The following information will be collected at baseline

1. Demographics - age, gender, rank, working status, medical category

2. Patient Reported Outcomes at baseline (Appendix A)

   1. Body Pain Diagram
   2. Pain, Enjoyment and General Activity Scale (PEG)
   3. Pain Disability Index
   4. Hospital Anxiety and Depressions Scale (HADS)
   5. Adapted Deployment Risk & Resilience Inventory 2 Section J: Unit Support Exercise Questionnaire
   6. Brief Trauma Questionnaire (BTQ)
   7. Litigation Status

The following information will be collected at follow up, defined by discontinuation of medication or continuation on medication associated with predefined measure of clinical efficacy

1. Medication Efficacy and Side effect Form - for each prescribed medication noted perceived efficacy, severity of side effects and general comments. This will be completed at either the time of medication discontinuation, or when no further changes to dosing is made.
2. Previous medication taken (Appendix B) - investigators will look specifically at commonly prescribed pain medications, including: nortriptyline, duloxetine, topiramate, gabapentin, pregabalin, opioids (ie morphine derivatives, tramadol, tapentadol, buprenorphine patch), Cesamet and plant based cannabis. If necessary, the patient's health record will be accessed to complete this record
3. Current medications
4. Smoking status and total starting/current dose

Clinical efficacy will be defined by achieving 5-8 on the Patient Global Impression of Change scale (PGIC). Medication selection will be done in accordance with current standard of care, patient informed consent and clinical experience. Prescription of medication will not be directed by the results of the genetics analytics. Doses will be adjusted if side effects permit and until clinical efficacy is achieved

Classification of inferred phenotypes (i.e. ultrarapid, normal, intermediate and poor metabolizer) will be consistent with the recently published guidance for allele function status. As noted, there are four possible scores for each tested medication, ranging from 1-4, which includes; 1) do not use 2) caution 3) use as directed 4) preferred. For the main analysis, the phenotypes will be grouped 1&2 (do not prescribe) and 3&4 (prescribe) and compared against whether patient responded or not to determine sensitivity and specificity of the genetic testing. Sub-analysis will determine for those that did not respond and whether this was a result of side effects or a lack of efficacy. From a functional standpoint for each recommendation the pharmacogenetics testing will classified into green (prescribe), yellow (caution), red (do no prescribe). All yellow outcomes will be reviewed to determine if the clinical information (ie dosing, smoking, and/or current medications), could allow for re-classification to a green or red recommendation for the purpose of the analysis.

The distribution of the prediction score will also be separately evaluated for medications actively taken by participants and for medications that had been discontinued. The distribution of prediction scores will be compared using ANOVA. Genetic prediction scores will be separately compared against participants reported efficacy and side effects profile using Spearman's correlation coefficient, and the respective p values will be calculated, and corrected for multiple comparison

Patient Care:

Participation in the current study will not impact patient care or impact decision making regarding medication. Each patient is simply evaluating the effects of the medications so that we can compare their experiences with the predictive abilities of genetic prediction score.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1J6L4
      • Canadian Forces Health Services Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The study population will be Canadian Forces members between the ages of 18-60 years old, suffering from chronic pain, seen within the Canadian Forces Ottawa Physical Medicine and Rehabilitation clinic (CFO-P).

Description

Inclusion Criteria:

• male and female between 18 and 60 years old
• seen within the CFO-P
• diagnosed by a physician with one or more chronic pain condition.

Exclusion Criteria:

• adults who are unable to give their own consent
• contraindications to a buccal swab
• uncontrolled mental health issues determined by clinical judgement without mental health treatment and/or presence of active suicidal ideation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with chronic pain; Patients seen in clinic agreeing to participate in trial by completing clinical questionnaires and genetic testing

Diagnostic test: Genetic test for drug response prediction; There is interest in whether genetic analysis of how a given drug is processed for a patient can help with rational drug choices (i.e. most efficacious, with least side effects/interactions, in the fastest time). This appears to have some early support in cardiac, psychiatric and acute pain studies. All participants enrolled in the study will provide consent and a buccal cell sample for genotyping and standard patient reported outcomes questionnaires at the beginning of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and Specificity of PGx testing for pain response	For the main analysis, the phenotypes will be grouped 1&2 (do not prescribe) and 3&4 (prescribe) and compared against whether patient responded or not to determine sensitivity and specificity of the genetic testing. Sub-analysis will determine for those that did not respond and whether this was a result of side effects or a lack of efficacy	up to 8 weeks post initial medication prescription

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and Specificity of PGx testing for side effects	For the main analysis, the phenotypes will be grouped 1&2 (do not prescribe) and 3&4 (prescribe) and compared against whether patient responded or not to determine sensitivity and specificity of the genetic testing. Sub-analysis will determine for those that did not respond and whether this was a result of side effects or a lack of efficacy	up to 8 weeks post initial medication prescription

Collaborators and Investigators

• Sponsor: Canadian Forces Health Services Centre Ottawa

Study record dates

Study Major Dates

• Study Start (Estimated): September 21, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 12, 2022
• First Submitted That Met QC Criteria: February 28, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 10, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain
• Other Study ID Numbers: 2020-043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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