Therapeutic Drug Monitoring and Pharmacogenomics Study of Methadone Therapy

NCT ID: NCT01059747

Last Updated: 2010-02-01

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-12-31

Brief Summary

Addiction has been regarded as one of the most serious health and social problems in Taiwan, and heroin is currently considered to be the major substance of abuse. The most widely used treatment to date is methadone replacement therapy. It is reported that to achieve a better clinical response and to avoid possible side effects, the blood level of methadone should remain in a certain level. However, the blood level of methadone is mediated by various factors besides dosage. Genetic variability in genes that encodes enzymes affecting methadone metabolism, target receptors of methadone, and drug-drug interaction by other medication patients take will all affect blood level. Therefore, therapeutic drug monitoring (TDM) and pharmacogenomic study is crucial for evaluating and predicting the clinical response, cause of side effects or toxicity, as well as studies on drug-drug interactions.

This is a cross-sectional study in order to evaluate the relationship between methadone plasma level and clinical response in patients under methadone maintenance therapy and to identify optimal therapeutic thresholds. HPLC will be used to analyze methadone and its metabolites. Our hypothesis is that methadone plasma levels in patients who are responsive to methadone maintenance therapy are higher than level in non-responsive patients, and higher plasma level leads to less severe withdrawal symptoms. We will also test if an optimal minimal dosage exists among these patients. In the meanwhile, we will aim to test if methadone level and clinical response is correlated with different genetic polymorphism. Candidate genes that involve in pharmacokinetic and pharmacodynamic process of methadone (e.g. CYP3A4, CYP3A5, CYP2B6, ABCB1, opioid mu receptor and kappa receptor) will be genotyped for these analyses.

The results of this study will provide clinical information of methadone treatment and pharmacogenomic data in Taiwanese for clinicians to achieve a better treatment outcome.

Conditions

Heroin-addicted Patients Who Undertook Methadone Maintenance Treatment

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

treatment group

no intervention applied

Intervention Type: OTHER

no intervention applied

Interventions

no intervention applied

no intervention applied

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Chinese ethnicity

2. Men or women above age of 18

3. Able to participate in a clinical assessment in Chinese (including Mandarin and Taiwanese dialects)

4. Diagnosis of Heroin dependence by DSM-IV definition

5. Enter methadone maintenance therapy for at least 3 months

6. No change of methadone dosage for the last week

7. Regularly took methadone for the last week

8. Individuals who have completed a written consent form

Exclusion Criteria

1. Patients with comorbid severe mental disorders including:

1. Organic mental disorders, or

2. Schizophrenia

2. Severe cognitive impairment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health Research Institutes, Taiwan

OTHER

Sponsor Role: lead

Responsible Party

Division of Mental Health and Addiction Medicine, National Health Research Instiutes, Taiwan

Principal Investigators

Sheng-Chang Wang, MD

Role: PRINCIPAL_INVESTIGATOR

National Health Research Institutes, Taiwan

Locations

Departments of Psychiatry, Wei-Gong Memorial Hospital

Miaoli, , Taiwan

Site Status: RECRUITING

Departments of Psychiatry, China Medical University and Hospital

Taichung, , Taiwan

Site Status: RECRUITING

Departments of Psychiatry, Taipei City Hospital Song-De Campus

Taipei, , Taiwan

Site Status: RECRUITING

Departments of Psychiatry, Taipei City Hospital Yang-Ming Campus

Taipei, , Taiwan

Site Status: RECRUITING

Departments of Psychiatry, En-Chu-Kong Hospital

Taipei County, , Taiwan

Site Status: RECRUITING

Departments of Psychiatry, Far-Eastern Memorial Hospital

Taipei County, , Taiwan

Site Status: RECRUITING

Departments of Psychiatry, Tao-yuan Psychiatric Center

Taoyuan District, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Chun-Yu Chen, MS

Role: CONTACT

cyc@nhri.org.tw

886-37-246166 ext. 36747

Facility Contacts

Happy Kuy-Lok Tan, MD, MPH

Role: primary

References

Liu SW, Liu YL, Hwang LL, Wang SC, Kuo HW, Wu SL, Dai YW, Liu SC, Ho IK, Chen AC, Hsiao CF, Tsou HH. Chemokine IP-10 is correlated with cardiac responses and status of infection with HIV and HCV in methadone maintenance patients. Int J Cardiol. 2015 Sep 1;194:36-8. doi: 10.1016/j.ijcard.2015.05.055. Epub 2015 May 12. No abstract available.

Reference Type: DERIVED

PMID: 26011262 (View on PubMed)

Tsai HJ, Wang SC, Tian JN, Chang TK, Ho IK, Hsiao CF, Chen CH, Tan HK, Lin L, Wu CS, Su LW, Huang CL, Yang YH, Liu ML, Lin KM, Liu YL. PXR polymorphisms interacted with CYP2B6 polymorphisms on methadone metabolites. J Clin Psychopharmacol. 2013 Feb;33(1):137-40. doi: 10.1097/01.jcp.0000426186.34421.de. No abstract available.

Reference Type: DERIVED

PMID: 23288240 (View on PubMed)

Wang SC, Tsou HH, Chen CH, Chen YT, Ho IK, Hsiao CF, Chou SY, Lin YF, Fang KC, Huang CL, Su LW, Fang YC, Liu ML, Wu HY, Lin KM, Liu SC, Kuo HW, Chiang IC, Chen AC, Tian JN, Liu YL. Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients. Eur Neuropsychopharmacol. 2012 Oct;22(10):695-703. doi: 10.1016/j.euroneuro.2012.02.002. Epub 2012 Mar 9.

Reference Type: DERIVED

PMID: 22406240 (View on PubMed)

Other Identifiers

98A1-PHPP41

Identifier Type: -

Identifier Source: org_study_id