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

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

Study Overview

• Status: Withdrawn
• Conditions: Non-cancerous Chronic Pain
• Intervention / Treatment: Other: Standard opioid prescription; Other: Pharmacogenetic analysis allowing personalized opioid prescription

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-Christophe Boyer, MD; Phone Number: 06 83 18 85 13; Email: jean.christophe.boyer@chu-nimes.fr

Study Locations

• France
  • Nîmes, France, 30029
    • CHU Nîmes
    • Principal Investigator: Jean-Christophe Boyer, MD
    • Principal Investigator: Olivier Bredeau, MD
    • Principal Investigator: Eric Viel, MD
    • Sub-Investigator: Nathalie Maignaut-Licata, MD
    • Sub-Investigator: Alexandre Evrard, MD
    • Sub-Investigator: Serge Lumbroso, MD
    • Sub-Investigator: Jean-Marie Kinowski, MD
    • Sub-Investigator: François JEDRYKA, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Prescription as standard	Other: Standard opioid prescription; Opioid prescription made without reference to patient genetic profile (tramadol, codeine or oxycodone)
EXPERIMENTAL: Pharmacogenetic-guided prescription	Other: Pharmacogenetic analysis allowing personalized opioid prescription; Genotypic of patient to determine optimal opioid treatment (tramadol, codeine or oxycodone)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2022
• Primary Completion (ANTICIPATED): December 1, 2023
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: April 6, 2018
• First Posted (ACTUAL): April 13, 2018

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Narcotics; Analgesics, Opioid
• Other Study ID Numbers: NIMAO/2017-02/JCB-01

Drug and device information, study documents

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