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

National Health Research Institutes, Taiwan

Status: Unknown

Conditions: Heroin-addicted Patients Who Undertook Methadone Maintenance Treatment

Treatments: Other: no intervention applied

Study type: Observational

Funder types: Other

Identifiers

NCT01059747

98A1-PHPP41

Details and patient eligibility

About

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.

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

500 participants in 1 patient group

treatment group

Treatment:

Other: no intervention applied