Variance of Oral Methadone Dosage: Description of Implicated Factors

Heroin Dependence Clinical Trial

— METHADOSE  

Official title:

Factors Associated With the Variance of Oral Methadone Dosage at Steady State of Maintenance Treatment: Description of Bio-markers of Phenotype and Genotype.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00894452
• Other study ID #: P070603
• Status: Completed
• Phase: N/A
• First received: March 31, 2009
• Last updated: September 28, 2016
• Start date: December 2008
• Est. completion date: May 2013

Study information

• Verified date: September 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to describe clinical, pharmacokinetic and genetic factors associated with the variance of oral methadone dosage for patients at the steady state of heroin dependence maintenance treatment. The hypothesis is that the investigators can predict 70% of the variance with few factors, including CYP 3A4 function measured with oral midazolam challenge.

Description:

Patients at the steady state of methadone maintenance treatment may receive oral dosage ranging from 5 to 130 mg per day in our clinical practice. This study is aimed at providing a comprehensive cross-sectional description of factors involved in this variance:

• comorbidity with addictive and psychiatric disorders

• severity of pre-existing heroin dependence

• function of CYP 3A4 enzyme assessed with oral midazolam challenge

• genetic polymorphisms of enzymes implicated in methadone pharmacokinetic and pharmacodynamic (CYPs, MDR1, OPRM1, COMT)

The expected result is a predictive equation of oral methadone dosage at steady state.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: May 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• heroin dependence

• under maintenance treatment with methadone

• at steady state: stable oral methadone dosage since 3 months at least

Exclusion Criteria:

• current heroin dependence or abuse

• current cocaine and/or alcohol and/or sedatives dependence

• pregnancy

Study Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Heroin Dependence

Locations

Country	Name	City	State
France	hospital Lariboisière-Fernand-WidalCity: PARIS	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (6)

Hajj A, Ksouda K, Peoc'h K, Curis E, Messali A, Deveaux LL, Bloch V, Prince N, Mouly S, Scherrmann JM, Lépine JP, Laplanche JL, Drici MD, Vorspan F. KCNH2 polymorphism and methadone dosage interact to enhance QT duration. Drug Alcohol Depend. 2014 Aug 1;1 — View Citation

Icick R, Peoc'h K, Karsinti E, Ksouda K, Hajj A, Bloch V, Prince N, Mouly S, Bellivier F, Lépine JP, Laplanche JL, Vorspan F. A cannabinoid receptor 1 polymorphism is protective against major depressive disorder in methadone-maintained outpatients. Am J A — View Citation

Icick R, Peoc'h K, Ksouda K, Bloch V, Laplanche JL, Lépine JP, Bellivier F, Vorspan F. OPRM1 polymorphism and lifetime suicide attempts among stabilized, methadone-maintained outpatients. Psychiatry Res. 2014 Aug 15;218(1-2):259-60. doi: 10.1016/j.psychre — View Citation

Karsinti E, Fortias M, Dupuy G, Ksouda K, Laqueille X, Simonpoli AM, Touzeau D, Avril E, Orizet C, Belforte B, Coeuru P, Polomeni P, Icick R, Jarroir M, Bloch V, Scott J, Lépine JP, Bellivier F, Vorspan F. Anxiety disorders are associated with early onset — View Citation

Marie-Claire C, Crettol S, Cagnard N, Bloch V, Mouly S, Laplanche JL, Bellivier F, Lepine JP, Eap C, Vorspan F. Variability of response to methadone: genome-wide DNA methylation analysis in two independent cohorts. Epigenomics. 2016 Feb;8(2):181-95. doi: — View Citation

Mouly S, Bloch V, Peoc'h K, Houze P, Labat L, Ksouda K, Simoneau G, Declèves X, Bergmann JF, Scherrmann JM, Laplanche JL, Lepine JP, Vorspan F. Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional activity CYP3A4	Functional activity CYP3A4 as measured by the ratio of metabolite / parent drug provided by the functional test the oral midazolam.	Day15	No