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

Drug Effect Clinical Trial

— MePhaCard  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04254731
• Other study ID #: 2012/793 REK
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: May 7, 2015
• Est. completion date: July 30, 2024

Study information

• Verified date: April 2024
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: July 30, 2024
• Est. primary completion date: June 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Adverse Drug Effect
• Arrhythmias, Cardiac
• Drug Effect
• Drug-Related Side Effects and Adverse Reactions
• Heart Arrhythmia

Intervention

Drug:
• Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)

Locations

Country	Name	City	State
Norway	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

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Country where clinical trial is conducted

Norway, 

References & Publications (1)

Havig SM, Berg-Pedersen RM, Krabseth HM, Muller LD, Haugaa K, Zare HK, Gjesdal K, Krajci P, Opdal MS. Effect on QTc interval by switching from methadone to equipotent R-methadone dose in methadone maintenance treatment patients. Basic Clin Pharmacol Toxicol. 2024 Apr;134(4):519-530. doi: 10.1111/bcpt.13982. Epub 2024 Feb 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.

External Links

•   abstract from EACPT 2019, see abstract 1168