KCNH2 Polymorphisms on the QTc Interval in Kelantanese Malays Patients Receiving Methadone Maintenance Therapy (MMT)

NCT03603158 | Completed

• 1 other identifier: USMKK/PPP/JEPeM 9221.3[5]
• Study Type: observational
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

Methadone maintenance therapy (MMT) is one of the modalities to prevent HIV transmission among injected drug users, particularly in opioid-dependent users. However, methadone-associated cardiotoxicity is one of the fatal adverse events that limit the widespread usage in certain groups of opioid-dependent patients. This is a cross-sectional study aimed to investigate the association between 4 KCNH2 SNPs (1539C\>T, in exon 6 of KCNH2 gene; 1956T\>C, in exon 8 of KCNH2 gene), 2350C\>T (in exon 9 of KCNH2 gene), 2690A\>C (Exon 11 of KCNH2 gene)) and prolongation of QTc interval in opioid-dependent Kelantanese Malays who are the recipients of Methadone Maintenance Therapy. The investigators hypothesized that subjects with minor alleles of those 4 SNPs will have longer QTc intervals than those with major alleles, adjusting for the effects of other confounding factors such as age and gender of the subjects, plasma methadone trough levels, hypokalemia, hypocalcemia and hypomagnesemia. The investigators also aimed to provide a model that will reliably predict the magnitude QTc based on the SNPs data and other covariates mentioned above. This will greatly assist in identifying methadone recipients who are at risk of developing prolonged QTc or the more fatal torsade de pointes.

Conditions

Opioid Dependence; Methadone Toxicity; HERG Gene Mutation

Keywords

HERG; KCNH2; METHADONE; OPIOID

Outcome Measures

Primary Outcomes (1)

• QTc Interval

  QT interval (measured in milliseconds) obtained from ECG reading that is then divided by the shortest R-R interval to the power of 0.33 (Fredericia's formula).

  First screening visit

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Kelantanese Malay opioid-dependent subjects who were on Methadone Maintenance Therapy (MMT) in the Eastern-coastal state of Kelantan, Malaysia.

You may qualify if:

• Opioid-dependent subjects aged 18 years and above
• Opioid-dependent subjects who were on Methadone Maintenance Therapy (MMT) for 6 months or longer and had stable plasma methadone concentration
• Malay ancestry up to 3 generations
• A history of good compliance with Directly-Observed Therapy (DOT)

You may not qualify if:

• Opioid-dependent subjects who were aggressive and had active psychiatric illnesses
• Opioid-dependent subjects with chronic medical and surgical illnesses
• Opioid-dependent subjects with cardiac structural defects
• Inability to communicate in Malay or English

Sponsors & Collaborators

• Universiti Sains Malaysia: lead

Study Sites (1)

Hospital Universiti Sains Malaysia

Kubang Kerian, Kelantan, 15350, Malaysia

Location

Related Publications (2)

• Koo SH, Ho WF, Lee EJ. Genetic polymorphisms in KCNQ1, HERG, KCNE1 and KCNE2 genes in the Chinese, Malay and Indian populations of Singapore. Br J Clin Pharmacol. 2006 Mar;61(3):301-8. doi: 10.1111/j.1365-2125.2005.02545.x.

  PMID: 16487223 RESULT

• 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.

  PMID: 24875677 RESULT

Related Links

• Abstract and full text
• Abstract

Biospecimen

Retention: SAMPLES WITH DNA

Genomic DNA extracted from peripheral leukocytes in 5 mls venous blood samples provided by all methadone recipients enrolled in this study.

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Muslih AbdulKarim Ibrahim, PhD

  Hawler University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: July 27, 2018
• Study Start: February 1, 2011
• Primary Completion: December 31, 2012
• Study Completion: December 31, 2012
• Last Updated: July 30, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)