Therapeutic Drug Monitoring and Pharmacogenomics Study of Methadone Therapy (M0108)

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.

Study Overview

• Status: Unknown
• Conditions: Heroin-addicted Patients Who Undertook Methadone Maintenance Treatment
• Intervention / Treatment: Other: no intervention applied

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

Study Locations

• Taiwan
  • Miaoli, Taiwan
    • Recruiting
    • Departments of Psychiatry, Wei-Gong Memorial Hospital
    • Principal Investigator: Ming-Lun Liu, MD
  • Taichung, Taiwan
    • Recruiting
    • Departments of Psychiatry, China Medical University and Hospital
    • Principal Investigator: Chieh-Liang Huang, MD
  • Taipei, Taiwan
    • Recruiting
    • Departments of Psychiatry, Taipei City Hospital Song-De Campus
    • Principal Investigator: Lien-Wen Su, MD
  • Taipei, Taiwan
    • Recruiting
    • Departments of Psychiatry, Taipei City Hospital Yang-Ming Campus
    • Principal Investigator: Yih-Hong Yang, MD
    • Sub-Investigator: Yung-Chun Fang, MD
  • Taipei County, Taiwan
    • Recruiting
    • Departments of Psychiatry, En-Chu-Kong Hospital
    • Principal Investigator: Li-Nen Lin, MD
    • Sub-Investigator: Yen-Feng Lin, MD
  • Taipei County, Taiwan
    • Recruiting
    • Departments of Psychiatry, Far-Eastern Memorial Hospital
    • Principal Investigator: Chi-Shin Wu, MD
    • Sub-Investigator: Kai-Chi Fang, MD
  • Tao-Yuan, Taiwan
    • Recruiting
    • Departments of Psychiatry, Tao-yuan Psychiatric Center
    • Contact: Happy Kuy-Lok Tan, MD, MPH
    • Principal Investigator: Happy Kuy-Lok Tan, MD, MPH
    • Sub-Investigator: Sun-Yuan Chou, MD
    • Sub-Investigator: Kuen-Hong Wu, 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

• Sampling Method: Non-Probability Sample

Study Population

heroin-addicted patients

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
treatment group	Other: no intervention applied; no intervention applied

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan
• Investigators: Principal Investigator: Sheng-Chang Wang, MD, National Health Research Institutes, Taiwan

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• M0108 Project Web Site

Study record dates

Study Major Dates

• Study Start: December 1, 2008

Study Registration Dates

• First Submitted: January 29, 2010
• First Submitted That Met QC Criteria: January 29, 2010
• First Posted (Estimate): February 1, 2010

Study Record Updates

• Last Update Posted (Estimate): February 1, 2010
• Last Update Submitted That Met QC Criteria: January 29, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Other Study ID Numbers: 98A1-PHPP41