Hair Testing to Assess Consumption of Illicit Psychotropic Agents and Alcohol by Patients Treated With High-dose Buprenorphine and Methadone. Search for a Pharmacogenetic Contribution to Low Efficacy of Substitution Medications

Justification and aims of the study: The principal aim of use of opiate substitutes such as methadone or high-dose buprenorphine (HDB) is to reduce the need or the desire to consume the opiate to which the patient is addicted. Adjustment of the initial dose and regular re-evaluation of the efficacy of treatment are key elements in the success of such management. While too high a dose can be responsible for side effects leading to abandonment of treatment, too low a dose can induce the reappearance or even the reinforcing of parallel consumption of other psychoactive substances, in particular cocaine, alcohol and cannabis. The principal aim of this project is to determine the course of parallel consumption in patients who have been receiving a maintenance dose of methadone or HDB for at least two months, by analysis of a sample of hair, a biological matrix which is innovative for this type of study. Hair testing establishes a retrospective profile of consumption. The secondary aims of this project are (i) to validate the French versions of Handelsman's subjective and objective opiate withdrawal scales and to seek a possible correlation between high scores on these scales and the presence of parallel consumption, and (ii) to seek an association between polyconsumption and common functional polymorphisms of metabolic enzymes of methadone and HDB.

Expected results: Hair testing, which has the particular advantage of a long detection window so that samples need only be taken at intervals, could improve the biological monitoring of patients on substitutive treatment.

Validation of the French version of Handelsman's scales of objective and subjective signs of opiate withdrawal and search for any correlation with parallel consumption will enable these scales to be used in daily practice for clinical surveillance of patients on substitutive treatment.

If a polymorphism of a metabolic enzyme of one or other of these molecules is detected, rapid genotyping of a simple saliva sample will be valuable in guiding the choice of medication when deciding on a treatment strategy

Study Overview

• Status: Unknown
• Conditions: Substance Abuse
• Intervention / Treatment: Other: hair and saliva samples

Detailed Description

Methodology: The two populations of patients, one treated with methadone, the other with HDB, will be recruited in accordance with the ethical principles of the declaration of Helsinki, during consultations at a center for addiction treatment. One hundred and ten patients will be included in each of the two populations. Written informed consent will be obtained from each patient. Anonymity will be respected at inclusion and throughout. Using a sample of hair, testing for and measurement of the principal drugs (opiates, cannabis, cocaine, amphetamines) and the specific marker of ethanol consumption, ethyl glucuronide, will be performed by chromatographic techniques (high-performance liquid chromatography and gas phase chromatography) together with detection by mass or tandem mass spectrometry. This non-invasive sampling is more informative than blood tests, as it gives a retrospective profile of an individual's consumption over several months. Treatment efficacy will also be assessed using Handelsman's subjective and objective opiate withdrawal scales. Lastly, polymorphisms of the metabolic enzymes of methadone and HDB will be sought by real-time PCR in a saliva sample, a method which gives similar results without the need for venous blood sampling.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne Laure Pelissier-Alicot; Phone Number: +33491384748; Email: anne-laure.pelissier@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13005
    • Recruiting
    • APHM
    • Contact: Anne-Laure Pelissier-Alicot; Phone Number: +33491384748

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:

• subjects followed for opiates substitute treatment
• patients treated by HDB or methadone for at least two months
• length of hair superior to 2 centimeters

Exclusion Criteria:

• patients treated by HDB or methadone for less than two months
• Patients with clinical signs of intolerance or opioid overdose
• opioid treatments
• neurological or psychiatric disease
• hepatic disease
• pregnancy
• patients in prison

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: buprenorphine; populations of patients treated with HDB will be recruited during consultations at a center for addiction treatment. One hundred and ten patients will be included. Written informed consent will be obtained from each patient. Anonymity will be respected at inclusion and throughout. Using a sample of hair, testing for and measurement of the principal drugs (opiates, cannabis, cocaine, amphetamines) and the specific marker of ethanol consumption, ethyl glucuronide, will be performed by chromatographic techniques (high-performance liquid chromatography and gas phase chromatography) together with detection by mass or tandem mass spectrometry. Treatment efficacy will also be assessed using Handelsman's subjective and objective opiate withdrawal scales. Lastly, polymorphisms of the metabolic enzymes of methadone and HDB will be sought by real-time PCR in a saliva sample, a method which gives similar results without the need for venous blood sampling.	Other: hair and saliva samples; Using a sample of hair, testing for and measurement of the principal drugs (opiates, cannabis, cocaine, amphetamines) and the specific marker of ethanol consumption, ethyl glucuronide, will be performed by chromatographic techniques (high-performance liquid chromatography and gas phase chromatography) together with detection by mass or tandem mass spectrometry. This non-invasive sampling is more informative than blood tests, as it gives a retrospective profile of an individual's consumption over several months. Saliva sample, a method which gives similar results without the need for venous blood sampling.
Active Comparator: methadone; populations of patients treated with methadone will be recruited during consultations at a center for addiction treatment. One hundred and ten patients will be included. Written informed consent will be obtained from each patient. Anonymity will be respected at inclusion and throughout. Using a sample of hair, testing for and measurement of the principal drugs (opiates, cannabis, cocaine, amphetamines) and the specific marker of ethanol consumption, ethyl glucuronide, will be performed by chromatographic techniques (high-performance liquid chromatography and gas phase chromatography) together with detection by mass or tandem mass spectrometry. Treatment efficacy will also be assessed using Handelsman's subjective and objective opiate withdrawal scales. Lastly, polymorphisms of the metabolic enzymes of methadone and HDB will be sought by real-time PCR in a saliva sample, a method which gives similar results without the need for venous blood sampling.	Other: hair and saliva samples; Using a sample of hair, testing for and measurement of the principal drugs (opiates, cannabis, cocaine, amphetamines) and the specific marker of ethanol consumption, ethyl glucuronide, will be performed by chromatographic techniques (high-performance liquid chromatography and gas phase chromatography) together with detection by mass or tandem mass spectrometry. This non-invasive sampling is more informative than blood tests, as it gives a retrospective profile of an individual's consumption over several months. Saliva sample, a method which gives similar results without the need for venous blood sampling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hair ANALYSIS	Hair testing which has the particular advantage of a long detection window so that samples need only be taken at intervals	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of the French version of Handelsman's scales	Validation of the French version of Handelsman's scales of objective and subjective signs of opiate withdrawal and search for any correlation with parallel consumption will enable these scales to be used in daily practice for clinical surveillance of patients on substitutive treatment.	36 months
polymorphism of a metabolic enzyme	If a polymorphism of a metabolic enzyme of one or other of these molecules is detected, rapid genotyping of a simple saliva sample will be valuable in guiding the choice of medication when deciding on a treatment strategy.	36 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: Anne-Laure Pelissier-Alicot, APHM

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): August 1, 2015
• Study Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: July 29, 2010
• First Submitted That Met QC Criteria: January 27, 2011
• First Posted (Estimate): January 28, 2011

Study Record Updates

• Last Update Posted (Estimate): August 29, 2014
• Last Update Submitted That Met QC Criteria: August 28, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: buprenorphine; patients; methadone; illicit consumption of psychotropic agents and alcohol
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: 2010-A00256-33 (Other Identifier: DRC)