Effects of Switching From Racemic Methadone to R-methadone on QTc Intervals

Study Overview
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Brief Summary
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Effects of switching from racemic methadone to R-methadone on serum methadone concentrations and QTc intervals

Detailed Description
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Racemic methadone may prolong the QTc interval, which is associated with fatal arrhythmias. In vitro studies have shown that R-methadone has less inhibitory effect than S-methadone on the voltage-gated potassium channel current, and is thus thought to have less effect on the QTc interval. The investigators hypothesized that switching from racemic to R-methadone would reduce the methadone serum concentration and also its effect on the QTc interval.

Official Title
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The Study of Potential Normalization of Cardiac Rhythm Following Drug Exchange From Chimeric Methadone to Active Methadone

Conditions
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Adverse Drug Effect, Drug Effect, Heart Arrhythmia

Intervention / Treatment
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* Drug: Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stabilized on daily methadone dose Not using other drugs of abuse QTc-time recorded automatically, patient inclusion if QTc interval was greater or equal to 450 ms Older than 18 years Can sign and understand a written Consent Exclusion Criteria: Can not cooperate regarding observed daily drug intake Serious psychiatric disease Untreated serious somatic disease Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients included were stabilized on per os methadone maintenance treatment and had automatically ECG recorded QTc interval greater or equal to 450 ms. The patients were switched to pure R-methadone per os (half dose of the racemic methadone used). Doses, serum drug concentrations, QTc-time were recorded before and after drug switch. Serum-electrolytes (Mg, K, Ca) and opioid withdrawal symptom scale (OWS) were also measured and scored before and after drug switch.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cross over study before and after drug switch<br>Stabilized on racemic methadone dose, switched to R-methadone of half racemic methadone dose. Cross over study, own control | Drug: Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)<br> <br> * Other names: Drugs provided from the pharmaceutical company called DnePharma AS (Den norske Eterfabrikk ( DnE), address Karihaugen 22, Oslo, Norway, drug delivered to patient from home nurse or pharmacy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of switching from racemic methadone to R-methadone on serum methadone concentrations. | Ten patients stabilized on racemic methadone dose were switched to R-methadone and effects on serum methadone concentrations were studied. Methadone concentrations (nmol/L) were measured by validated high pressure liquid chromatography coupled to mass spectrometry detection (LC-MSMS). | Time frame of each patient form inclusion to end study was 35-40 days. | 
| Effects of switching from racemic methadone to R-methadone on QTc interval | In ten patients QTc intervals were recorded on racemic methadone treatment at Cmin and Cmax of methadone drug concentrations and likewise after the shift to R-methadone. QT intervals (ms) on ECG were recorded automatically and read manually by experienced cardiologists. | Time frame of each patient form inclusion to end study was 35-40 days. | 
| Effects of switching from racemic methadone to R-methadone on opioid withdrawal symptoms (OWS) | Ten patients: each patients had OWS recorded on racemic and R-methadone treatment using OWS. | Time frame of each patient form inclusion to end study was 35-40 days. | 
| Effects of switching from racemic methadone to R-methadone, stability of serum electrolytes (Ca, Mg, K) in patients | Ten patients: samples for serum electrolytes were collected before and after switch to R-methadone. Measured by routine analysis at Cobas 8000 (unit mmol/L) | Time frame of each patient form inclusion to end study was 35-40 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Racemic methadone, R-methadone, QTc interval, Methadone maintenance treatment patients