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

Phase 4

Active, not recruiting

• Conditions: Adverse Drug Effect; Drug Effect; Heart Arrhythmia
• Interventions: Drug: Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)

• Registration Number: NCT04254731
• Lead Sponsor: Oslo University Hospital

Brief Summary

Effects of switching from racemic methadone to R-methadone on serum methadone concentrations and QTc intervals

Detailed Description

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.

Study Timeline

• Study Start: 2015-05-07
• Primary Completion: 2018-06-27
• Study First Submitted: 2020-01-06
• Study First Submitted QC: 2020-01-31
• Study First Posted: 2020-02-05
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-02
• Last Update Posted: 2024-04-03
• Study Completion: 2024-07-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cross over study before and after drug switch	Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)	Stabilized on racemic methadone dose, switched to R-methadone of half racemic methadone dose. Cross over study, own control

Primary Outcome Measures

Name	Time	Method
Effects of switching from racemic methadone to R-methadone on serum methadone concentrations.	Time frame of each patient form inclusion to end study was 35-40 days.	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).
Effects of switching from racemic methadone to R-methadone on QTc interval	Time frame of each patient form inclusion to end study was 35-40 days.	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.
Effects of switching from racemic methadone to R-methadone on opioid withdrawal symptoms (OWS)	Time frame of each patient form inclusion to end study was 35-40 days.	Ten patients: each patients had OWS recorded on racemic and R-methadone treatment using OWS.
Effects of switching from racemic methadone to R-methadone, stability of serum electrolytes (Ca, Mg, K) in patients	Time frame of each patient form inclusion to end study was 35-40 days.	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)

Trial Locations

Locations (3)

Department of Pharmacology , Oslo University Hospital; 🇳🇴 Oslo, Norway

Department of Pharmacology and Department of Substance Use Disorder, Oslo University Hospital; 🇳🇴 Oslo, Norway

Department of Substance Use Disorder, Oslo University Hospital; 🇳🇴 Oslo, Norway