Adverse Drug EffectPhase 4MePhaCardNCT04254731
Effects of Switching From Racemic Methadone to R-methadone on QTc Intervals
A Phase 4 study testing Same individuals treated with racemic methadone and switched to levomethadone (R-methadone) in people with Adverse Drug Effect and Drug Effect, run by Oslo University Hospital at 3 sites in Norway.
Trial summary
Effects of switching from racemic methadone to R-methadone on serum methadone concentrations and QTc intervals Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Adverse Drug Effect, Drug Effect, Heart Arrhythmia
- What is being tested?
- Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 3 sitesNorway
- Study dates
- 7 May 2015to 30 Jul 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Can not cooperate regarding observed daily drug intake
- Serious psychiatric disease
- Untreated serious somatic disease
- Pregnancy
Trial locations and contacts
3 sites in 1 country.
Norway3 sites
Department of Pharmacology , Oslo University Hospital
Oslo, 0424
Department of Pharmacology and Department of Substance Use Disorder, Oslo University Hospital
Oslo, 0424
Department of Substance Use Disorder, Oslo University Hospital
Oslo, 0424
About this study
Official title: The Study of Potential Normalization of Cardiac Rhythm Following Drug Exchange From Chimeric Methadone to Active Methadone
Effects of switching from racemic methadone to R-methadone on serum methadone concentrations and QTc intervals
Read the 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.
- Conditions
- Adverse Drug Effect, Drug Effect, Heart Arrhythmia
- Being tested
- Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)
- Keywords
- Racemic methadone, R-methadone, QTc interval, Methadone maintenance treatment patients
- Medical subject headings
- Drug-Related Side Effects and Adverse Reactions, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)Drug
Also called 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
| Study group | Role | What they receive |
|---|---|---|
| Cross over study before and after drug switch | Other | Stabilized on racemic methadone dose, switched to R-methadone of half racemic methadone dose. Cross over study, own control Receives: Drug: Same individuals treated with racemic methadone and switched to levomethadone (R-methadone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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)
Measured: Time frame of each patient form inclusion to end study was 35-40 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start7 May 2015
- Primary completion27 Jun 2018
- Study completion30 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adverse Drug EffectStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mimi Stokke Opdal, Oslo University Hospital
- Investigators
- Mimi Stokke S Opdal, MD, PhD, Study director, Oslo University Hospital and University of OsloPeter Krajci, MD, PhD, Study director, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04254731
- Sponsor's protocol ID
- 2012/793 REK
- Acronym
- MePhaCard
- Status last verified
- Apr 2024
- First submitted
- 6 Jan 2020
- Last updated
- 3 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD can be shared when the manuscript has been accepted for publication.
Publications
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.
PubMed 38308508
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Study of Potential Normalization of Cardiac Rhythm Following Drug Exchange From Chimeric Methadone to Active Methadone
- ClinicalTrials.gov ID
- NCT04254731
- Acronym / sponsor ID
- MePhaCard / 2012/793 REK
- Conditions
- Adverse Drug Effect, Drug Effect, Heart Arrhythmia
- Keywords
- Racemic methadone, R-methadone, QTc interval, Methadone maintenance treatment patients
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 7 May 2015 (actual)
- Primary completion
- 27 Jun 2018 (actual)
- Study completion
- 30 Jul 2024 (estimated)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Cross over study before and after drug switch | Other | Drug: 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- Can not cooperate regarding observed daily drug intake
- Serious psychiatric disease
- Untreated serious somatic disease
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)Also: 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 | Drug | Cross over study before and after drug switch |
Primary outcome
Effects of switching from racemic methadone to R-methadone on serum methadone concentrations.
Time frame: 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: 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: 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: 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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Background: PubMed 38308508Havig 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.
- abstract from EACPT 2019, see abstract 1168Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD can be shared when the manuscript has been accepted for publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mimi Stokke S Opdal, MD, PhD study director
Oslo University Hospital and University of Oslo
Peter Krajci, MD, PhD study director
Oslo University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Same individuals treated with racemic methadone and switched to levomethadone (R-methadone) in people with Adverse Drug Effect and Drug Effect, run by Oslo University Hospital at 3 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of switching from racemic methadone to R-methadone on serum methadone concentrations. (time frame: Time frame of each patient form inclusion to end study was 35-40 days.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04254731, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.