Comparison of Standard Opioid Prescription Versus Prescription Guided by Pharmacogenetic Analysis in Patients With Non-cancerous Chronic Pain.

Study Overview
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Brief Summary
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The investigators hypothesize that opioid prescription guided by patient pharmacogenetic profile will diminish opioid-associated undesirable effects by 50% and improve medication compliance.

Official Title
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Comparison of Standard Opioid Prescription Versus Prescription Guided by Pharmacogenetic Analysis in Patients With Non-cancerous Chronic Pain.

Conditions
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Non-cancerous Chronic Pain

Intervention / Treatment
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* Other: Pharmacogenetic analysis allowing personalized opioid prescription
* Other: Standard opioid prescription


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must have given their free and informed consent and signed the consent form The patient must be a member or beneficiary of a health insurance plan The patient is at least 18 years old The patient will be available for all visits Patients suffer from non-cancerous chronic pain according to HAS criteria Patient not having taking opioids in previous 2 months Patient indicated for prescription of opioids (oxycodone, codeine or tramadol) or patient not responding to first line treatment Exclusion Criteria: The subject is participating in an category I interventional study, or is in a period of exclusion determined by a previous study The subject refuses to sign the consent It is impossible to give the subject informed information The patient is under safeguard of justice or state guardianship The patient is pregnant or breastfeeding The patient is likely to procreate and does not use an effective method of contraception (contraceptive ring, surgical contraception, implant, patch, contraceptive pill, male and female condoms, IUD) There is a contra-indication for opioid use Patient with an addiction risk (score ≥ 8 on ORT scale).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prescription as standard<br> | Other: Standard opioid prescription<br>* Opioid prescription made without reference to patient genetic profile (tramadol, codeine or oxycodone)<br>|
| Experimental: Pharmacogenetic-guided prescription<br> | Other: Pharmacogenetic analysis allowing personalized opioid prescription<br>* Genotypic of patient to determine optimal opioid treatment (tramadol, codeine or oxycodone)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare presence/absence undesirable events associated to opioid between groups from predefined list | Presence/absence of at least one undesirable event of at least grade 3 according to list in Annex 17.5 of the protocol | Month 1 | 
| Compare presence/absence undesirable events associated to opioid between groups from predefined list | Presence/absence of at least one undesirable event of at least grade 3 according to list in Annex 17.5 of the protocol | Month 2 | 
| Compare presence/absence undesirable events associated to opioid between groups from predefined list | Presence/absence of at least one undesirable event of at least grade 3 according to list in Annex 17.5 of the protocol | Month 3 | 
| Compare presence/absence undesirable events associated to opioid between groups | Presence/absence of at least one undesirable event of at least grade 3 according to Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Month 1 | 
| Compare presence/absence undesirable events associated to opioid between groups | Presence/absence of at least one undesirable event of at least grade 3 according to Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Month 2 | 
| Compare presence/absence undesirable events associated to opioid between groups | Presence/absence of at least one undesirable event of at least grade 3 according to Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of undesirable events associated to opioid between groups | Total number of undesirable event of at least grade 3 according to list in protocol | Month 1 | 
| Number of undesirable events associated to opioid between groups | Total number of undesirable event of at least grade 3 according to list in protocol | Month 2 | 
| Number of undesirable events associated to opioid between groups | Total number of undesirable event of at least grade 3 according to list in protocol | Month 3 | 
| Number of undesirable events associated to opioid between groups | Total number of undesirable event of at least grade 3 according to Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Month 1 | 
| Number of undesirable events associated to opioid between groups | Total number of undesirable event of at least grade 3 according to Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Month 2 | 
| Number of undesirable events associated to opioid between groups | Total number of undesirable event of at least grade 3 according to Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Month 3 | 
| Compare clinical therapeutic efficacy between groups | Patient Global Impression of Change (PGIC) score; value between 1-7 | Month 1 | 
| Compare clinical therapeutic efficacy between groups | Patient Global Impression of Change (PGIC) score; value between 1-7 | Month 2 | 
| Compare clinical therapeutic efficacy between groups | Patient Global Impression of Change (PGIC) score; value between 1-7 | Month 3 | 
| Compare patient-reported pain between groups | Visual analog scare 1-10 | Day 0 | 
| Compare patient-reported pain between groups | Visual analog scare 1-10 | Week 2 | 
| Compare patient-reported pain between groups | Visual analog scare 1-10 | Month 1 | 
| Compare patient-reported pain between groups | Visual analog scare 1-10 | Month 2 | 
| Compare patient-reported pain between groups | Visual analog scare 1-10 | Month 3 | 
| Compare neuropathic pain between groups | DN4 score (Douleur Neuropathique 4 Questions); score between 0-10 | Day 0 | 
| Compare neuropathic pain between groups | DN4 score (Douleur Neuropathique 4 Questions); score between 0-10 | Month 1 | 
| Compare neuropathic pain between groups | DN4 score (Douleur Neuropathique 4 Questions); score between 0-10 | Month 2 | 
| Compare neuropathic pain between groups | DN4 score (Douleur Neuropathique 4 Questions); score between 0-10 | Month 3 | 
| Compare benefit/risk ratio of treatment between groups | Overall Benefit of Analgesics Score (OBAS); score between 0-32 | Month 1 | 
| Compare benefit/risk ratio of treatment between groups | Overall Benefit of Analgesics Score (OBAS); score between 0-32 | Month 2 | 
| Compare benefit/risk ratio of treatment between groups | Overall Benefit of Analgesics Score (OBAS); score between 0-32 | Month 3 | 
| Compare quality of life between patients in each group | Quality of life Short Form 12 (SF-12) questionnaire; score between 0-100 | Day 0 | 
| Compare quality of life between patients in each group | Quality of life Short Form 12 (SF-12) questionnaire; score between 0-100 | Month 3 | 
| Compare medication compliance between groups | Serum concentration of tramadol, codeine or oxycodone and their metabolites by Liquid chromatography-tandem mass spectrometry (LC-MS-MS) | Month 1 | 
| Compare medication compliance between groups | Serum concentration of tramadol, codeine or oxycodone and their metabolites by Liquid chromatography-tandem mass spectrometry (LC-MS-MS) | Month 2 | 
| Compare medication compliance between groups | Serum concentration of tramadol, codeine or oxycodone and their metabolites by Liquid chromatography-tandem mass spectrometry (LC-MS-MS) | Month 3 | 
| Qualitive comparison of medication compliance between groups | Presence/absence of opioids or metabolites in serum | Month 1 | 
| Qualitive comparison of medication compliance between groups | Presence/absence of opioids or metabolites in serum | Month 2 | 
| Qualitive comparison of medication compliance between groups | Presence/absence of opioids or metabolites in serum | Month 3 | 
| Serum concentration of tramadol, codeine or oxycodone and their metabolites by Liquid chromatography-tandem mass spectrometry (LC-MS-MS) | Opioids Risk Tool (ORT): scores of 0-3 (low risk), 4-7 (moderate risk), or ≥ 8 (high risk) | Day 0 | 
| Compare observed medication misuse between groups | Prescription Opioid Misuse Index (POMI) | Month 1 | 
| Compare observed medication misuse between groups | Prescription Opioid Misuse Index (POMI) | Month 2 | 
| Compare observed medication misuse between groups | Prescription Opioid Misuse Index (POMI) | Month 3 | 
| Correlation between predicted phenotype and observed metabolic ratios | Products/substrate ratio measured by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) | Month 1 | 
| Correlation between predicted phenotype and observed metabolic ratios | Products/substrate ratio measured by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) | Month 2 | 
| Correlation between predicted phenotype and observed metabolic ratios | Products/substrate ratio measured by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) | Month 3 | 
| Metabolic profile of patients | Extensive Metaboliser, Intermediate Metaboliser, Poor Metaboliser or Ultra-rapid Metaboliser according to CYP2D6 phenotype and polymorphism of the glucuronyl transferase gene UGT2B7 | Month 1 | 
| Metabolic profile of patients | Extensive Metaboliser, Intermediate Metaboliser, Poor Metaboliser or Ultra-rapid Metaboliser according to CYP2D6 phenotype and polymorphism of the glucuronyl transferase gene UGT2B7 | Month 2 | 
| Metabolic profile of patients | Extensive Metaboliser, Intermediate Metaboliser, Poor Metaboliser or Ultra-rapid Metaboliser according to CYP2D6 phenotype and polymorphism of the glucuronyl transferase gene UGT2B7 | Month 3 | 
| Correlation between saliva and plasma concentration of opioids | Concentration of tramadol, codeine or oxycodone and their metabolites by Liquid chromatography-tandem mass spectrometry (LC-MS-MS) | Month 1 | 
| Correlation between saliva and plasma concentration of opioids | Concentration of tramadol, codeine or oxycodone and their metabolites by Liquid chromatography-tandem mass spectrometry (LC-MS-MS) | Month 2 | 
| Correlation between saliva and plasma concentration of opioids | Concentration of tramadol, codeine or oxycodone and their metabolites by Liquid chromatography-tandem mass spectrometry (LC-MS-MS) | Month 3 |