Heroin DependenceMETHADOSENCT00894452
Variance of Oral Methadone Dosage: Description of Implicated Factors
An observational study of Heroin Dependence, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heroin Dependence
- How many people
- 210 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2008to May 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Defined population: participants or population are selected based on predefined criteria
Who may be able to join
- heroin dependence
- under maintenance treatment with methadone
- at steady state: stable oral methadone dosage since 3 months at least
Who cannot join
- current heroin dependence or abuse
- current cocaine and/or alcohol and/or sedatives dependence
- pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the detailed 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.
- Conditions
- Heroin Dependence
- Keywords
- Methadone, CYP, OPRM1, MDR1, COMT, Midazolam challenge
- Medical subject headings
- Heroin Dependence
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional activity CYP3A4
Functional activity CYP3A4 as measured by the ratio of metabolite / parent drug provided by the functional test the oral midazolam.
Measured: Day15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2009 (estimated)
- Study startDec 2008
- Primary completionApr 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Heroin DependenceStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Florence VORSPAN, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00894452
- Sponsor's protocol ID
- P070603
- Acronym
- METHADOSE
- Status last verified
- Sep 2016
- First submitted
- 31 Mar 2009
- Last updated
- 29 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Hajj A, Ksouda K, Peoc'h K, Curis E, Messali A, Deveaux LL, Bloch V, Prince N, Mouly S, Scherrmann JM, Lepine JP, Laplanche JL, Drici MD, Vorspan F. KCNH2 polymorphism and methadone dosage interact to enhance QT duration. Drug Alcohol Depend. 2014 Aug 1;141:34-8. doi: 10.1016/j.drugalcdep.2014.04.027. Epub 2014 May 14.
PubMed 24875677Icick R, Peoc'h K, Ksouda K, Bloch V, Laplanche JL, Lepine 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.psychres.2014.04.035. Epub 2014 Apr 24. No abstract available.
PubMed 24813900Mouly S, Bloch V, Peoc'h K, Houze P, Labat L, Ksouda K, Simoneau G, Decleves 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 enzyme activity. Br J Clin Pharmacol. 2015 Jun;79(6):967-77. doi: 10.1111/bcp.12576.
PubMed 25556837Karsinti 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, Lepine JP, Bellivier F, Vorspan F. Anxiety disorders are associated with early onset of heroin use and rapid transition to dependence in methadone maintained patients. Psychiatry Res. 2016 Nov 30;245:423-426. doi: 10.1016/j.psychres.2016.04.064. Epub 2016 Jul 19.
PubMed 27620325Marie-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: 10.2217/epi.15.110. Epub 2016 Jan 21.
PubMed 26792095Icick R, Peoc'h K, Karsinti E, Ksouda K, Hajj A, Bloch V, Prince N, Mouly S, Bellivier F, Lepine JP, Laplanche JL, Vorspan F. A cannabinoid receptor 1 polymorphism is protective against major depressive disorder in methadone-maintained outpatients. Am J Addict. 2015 Oct;24(7):613-20. doi: 10.1111/ajad.12273. Epub 2015 Sep 1.
PubMed 26331953Icick R, Vorspan F, Karsinti E, Ksouda K, Lepine JP, Brousse G, Mouly S, Bellivier F, Bloch V. Gender-specific study of recurrent suicide attempts in outpatients with multiple substance use disorders. J Affect Disord. 2018 Dec 1;241:546-553. doi: 10.1016/j.jad.2018.08.076. Epub 2018 Aug 13.
PubMed 30153638
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00894452
- Acronym / sponsor ID
- METHADOSE / P070603
- Conditions
- Heroin Dependence
- Keywords
- Methadone, CYP, OPRM1, MDR1, COMT, Midazolam challenge
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Apr 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 7 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Defined population: participants or population are selected based on predefined criteria
Key inclusion criteria (3 listed)
- heroin dependence
- under maintenance treatment with methadone
- at steady state: stable oral methadone dosage since 3 months at least
Key exclusion criteria (3 listed)
- current heroin dependence or abuse
- current cocaine and/or alcohol and/or sedatives dependence
- pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Functional activity CYP3A4
Time frame: Day15
Functional activity CYP3A4 as measured by the ratio of metabolite / parent drug provided by the functional test the oral midazolam.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Results publication: PubMed 24875677Hajj A, Ksouda K, Peoc'h K, Curis E, Messali A, Deveaux LL, Bloch V, Prince N, Mouly S, Scherrmann JM, Lepine JP, Laplanche JL, Drici MD, Vorspan F. KCNH2 polymorphism and methadone dosage interact to enhance QT duration. Drug Alcohol Depend. 2014 Aug 1;141:34-8. doi: 10.1016/j.drugalcdep.2014.04.027. Epub 2014 May 14.
- Results publication: PubMed 24813900Icick R, Peoc'h K, Ksouda K, Bloch V, Laplanche JL, Lepine 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.psychres.2014.04.035. Epub 2014 Apr 24. No abstract available.
- Results publication: PubMed 25556837Mouly S, Bloch V, Peoc'h K, Houze P, Labat L, Ksouda K, Simoneau G, Decleves 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 enzyme activity. Br J Clin Pharmacol. 2015 Jun;79(6):967-77. doi: 10.1111/bcp.12576.
- Results publication: PubMed 27620325Karsinti 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, Lepine JP, Bellivier F, Vorspan F. Anxiety disorders are associated with early onset of heroin use and rapid transition to dependence in methadone maintained patients. Psychiatry Res. 2016 Nov 30;245:423-426. doi: 10.1016/j.psychres.2016.04.064. Epub 2016 Jul 19.
- Results publication: PubMed 26792095Marie-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: 10.2217/epi.15.110. Epub 2016 Jan 21.
- Results publication: PubMed 26331953Icick R, Peoc'h K, Karsinti E, Ksouda K, Hajj A, Bloch V, Prince N, Mouly S, Bellivier F, Lepine JP, Laplanche JL, Vorspan F. A cannabinoid receptor 1 polymorphism is protective against major depressive disorder in methadone-maintained outpatients. Am J Addict. 2015 Oct;24(7):613-20. doi: 10.1111/ajad.12273. Epub 2015 Sep 1.
- Derived from this study: PubMed 30153638Icick R, Vorspan F, Karsinti E, Ksouda K, Lepine JP, Brousse G, Mouly S, Bellivier F, Bloch V. Gender-specific study of recurrent suicide attempts in outpatients with multiple substance use disorders. J Affect Disord. 2018 Dec 1;241:546-553. doi: 10.1016/j.jad.2018.08.076. Epub 2018 Aug 13.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florence VORSPAN, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heroin Dependence, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional activity CYP3A4 (time frame: Day15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00894452, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2016.