Clinical trial NCT01059747: Therapeutic Drug Monitoring and Pharmacogenomics Study of Methadone Therapy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Heroin-addicted Patients Who Undertook Methadone Maintenance Treatment
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
First posted: 2010-02-01
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: heroin-addicted patients

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.


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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Miaoli
country: Taiwan
facility: Departments of Psychiatry, Wei-Gong Memorial Hospital
city: Taichung
country: Taiwan
facility: Departments of Psychiatry, China Medical University and Hospital
city: Taipei County
country: Taiwan
facility: Departments of Psychiatry, En-Chu-Kong Hospital
city: Taipei County
country: Taiwan
facility: Departments of Psychiatry, Far-Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: Departments of Psychiatry, Taipei City Hospital Song-De Campus
city: Taipei
country: Taiwan
facility: Departments of Psychiatry, Taipei City Hospital Yang-Ming Campus
city: Tao-Yuan
country: Taiwan
facility: Departments of Psychiatry, Tao-yuan Psychiatric Center
Study officials:
affiliation: National Health Research Institutes, Taiwan
name: Sheng-Chang Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.