Andersen Tawil SyndromePhase 2NCT06205550
N-of-1 in ATS and MEPPC
A Phase 2 study testing Flecainide and Flecainide + beta-blocker in people with Andersen Tawil Syndrome and Multifocal Ectopic Purkinje-related Premature Contractions, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Trial summary
Rationale: Andersen-Tawil syndrome (ATS) is a very rare heritable cardiac arrhythmia syndrome that is characterized by the triad of periodic paralysis, physical dysmorphisms, and ventricular arrhythmias, including bidirectional ventricular tachycardia (VT), polymorphic VT, and frequent multifocal premature ventricular… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Andersen Tawil Syndrome, Multifocal Ectopic Purkinje-related Premature Contractions
- What is being tested?
- Flecainide and Flecainide + beta-blocker
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Mar 2025to Oct 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- One of the following two primary diagnostic criteria A. Clinical diagnosis of ATS. Genetically confirmed diagnosis (i.e. class 4 or 5 KCNJ2 variant) is not required B. Clinical diagnosis of MEPPC and carrier of associated class 4 or 5 SCN5A variant
- Has demonstrated a disease phenotype of ATS or MEPPC including ventricular arrhythmia burden at any point during follow-up on Holter monitor or other rhythm monitoring device (i.e. loop recorder, ECG patch)
- Is currently treated with flecainide
- Age ≥ 18 years
Who cannot join
- Pregnancy
- Contra-indication to study medication (see section 7.4)
- Significant structural heart disease (left ventricular ejection fraction <50%, history or signs of coronary ischemia, suspicion or definitive diagnosis of cardiomyopathy, or moderate/severe valve regurgitation)
- Suspicion or definitive diagnosis of another (heritable) arrhythmia syndrome, e.g. Brugada syndrome, early repolarization syndrome or catecholaminergic polymorphic ventricular tachycardia
- Presence of a short (<350 ms) or prolonged (>480 ms) heart-rate corrected QT interval on the resting ECG at baseline
- History of therapy refractory ventricular arrhythmia or intolerable side-effects on an adequate dose of any study medication, as determined by the treating cardiologist
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- Serious known comorbid disease with a life expectancy of less than two years
- Ongoing medical condition that is deemed by the principal investigator to interfere with the conduct or assessments of the study or safety of the subjects
- Circumstances that prevent follow-up
- Inability to take orally administered tablets
- Inability to provide informed consent
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Optimal Drug Therapy for the Suppression of Ventricular Arrhythmias in Andersen-Tawil Syndrome and Multifocal Ectopic Purkinje-related Premature Contractions: a Series of N-of-1 Trials
Rationale: Andersen-Tawil syndrome (ATS) is a very rare heritable cardiac arrhythmia syndrome that is characterized by the triad of periodic paralysis, physical dysmorphisms, and ventricular arrhythmias, including bidirectional ventricular tachycardia (VT), polymorphic VT, and frequent multifocal premature ventricular contractions (PVCs). Multifocal ectopic Purkinje-related premature contractions (MEPPC) is a very rare syndrome characterized by frequent multifocal PVCs with relatively narrow QRS width. In both conditions, patients most often present with palpitations, but syncope and sudden cardiac arrest have also been reported. Left untreated, the large burden of PVCs can lead to PVC-induced cardiomyopathy. A number of therapeutic strategies are suggested in these conditions, but there is a lack of high-quality evidence on their efficacy.
Objective: To investigate the efficacy of various therapeutic strategies for reducing ventricular ectopy burden in patients with ATS or MEPPC.
Read more
Study design: Aggregated series of randomized, open-label N-of-1 trials. Each N-of-1 trial will consist of at least 2 treatment sets, each of which comprise two 7-day periods of treatment with therapy A and B, in a semi-randomized, counterbalanced order.
Study population: Adult patients with ATS or MEPPC on flecainide therapy.
Intervention: For ATS, flecainide monotherapy will be compared with combination therapy of flecainide and a β-blocker or calcium channel blocker. For MEPPC, flecainide monotherapy will be compared with combination therapy of flecainide and a β-blocker or calcium channel blocker (phase 1), and flecainide will be compared with quinidine (phase 2).
Main study endpoint: Ventricular ectopy burden on electrocardiographic monitoring.
- Being tested
- Flecainide, Flecainide + beta-blocker
- Medical subject headings
- Andersen Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlecainideDrug
Flecainide monotherapy
Flecainide + beta-blockerDrug
Flecainide + beta-blocker
| Study group | Role | What they receive |
|---|---|---|
| Flecainide + beta-blocker | Active comparator | Not described Receives: Drug: Flecainide + beta-blocker |
| Flecainide monotherapy | Experimental | Not described Receives: Drug: Flecainide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventricular ectopy burden
Measured: 5 24-hour periods per treatment period
Secondary outcomes (1)
Duration of longest ventricular tachycardia
Measured: 5 24-hour periods per treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2024
- Study startMar 2025 (estimated)
- Primary completionOct 2025 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Andersen Tawil SyndromeStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christian van der Werf, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06205550
- Sponsor's protocol ID
- ATS2023
- Status last verified
- Jan 2025
- First submitted
- 29 Dec 2023
- Last updated
- 29 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Drug Therapy for the Suppression of Ventricular Arrhythmias in Andersen-Tawil Syndrome and Multifocal Ectopic Purkinje-related Premature Contractions: a Series of N-of-1 Trials
- ClinicalTrials.gov ID
- NCT06205550
- Acronym / sponsor ID
- ATS2023
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Mar 2025 (estimated)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 16 Jan 2024 (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.
Rationale: Andersen-Tawil syndrome (ATS) is a very rare heritable cardiac arrhythmia syndrome that is characterized by the triad of periodic paralysis, physical dysmorphisms, and ventricular arrhythmias, including bidirectional ventricular tachycardia (VT), polymorphic VT, and frequent multifocal premature ventricular contractions (PVCs). Multifocal ectopic Purkinje-related premature contractions (MEPPC) is a very rare syndrome characterized by frequent multifocal PVCs with relatively narrow QRS width. In both conditions, patients most often present with palpitations, but syncope and sudden cardiac arrest have also been reported. Left untreated, the large burden of PVCs can lead to PVC-induced cardiomyopathy. A number of therapeutic strategies are suggested in these conditions, but there is a lack of high-quality evidence on their efficacy.
Objective: To investigate the efficacy of various therapeutic strategies for reducing ventricular ectopy burden in patients with ATS or MEPPC.
Study design: Aggregated series of randomized, open-label N-of-1 trials. Each N-of-1 trial will consist of at least 2 treatment sets, each of which comprise two 7-day periods of treatment with therapy A and B, in a semi-randomized, counterbalanced order.
Study population: Adult patients with ATS or MEPPC on flecainide therapy.
Intervention: For ATS, flecainide monotherapy will be compared with combination therapy of flecainide and a β-blocker or calcium channel blocker. For MEPPC, flecainide monotherapy will be compared with combination therapy of flecainide and a β-blocker or calcium channel blocker (phase 1), and flecainide will be compared with quinidine (phase 2).
Main study endpoint: Ventricular ectopy burden on electrocardiographic monitoring.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Flecainide + beta-blocker | Active comparator | Drug: Flecainide + beta-blocker |
| Flecainide monotherapy | Experimental | Drug: Flecainide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- One of the following two primary diagnostic criteria A. Clinical diagnosis of ATS. Genetically confirmed diagnosis (i.e. class 4 or 5 KCNJ2 variant) is not required B. Clinical diagnosis of MEPPC and carrier of associated class 4 or 5 SCN5A variant
- Has demonstrated a disease phenotype of ATS or MEPPC including ventricular arrhythmia burden at any point during follow-up on Holter monitor or other rhythm monitoring device (i.e. loop recorder, ECG patch)
- Is currently treated with flecainide
- Age ≥ 18 years
Key exclusion criteria (11 listed)
- Pregnancy
- Contra-indication to study medication (see section 7.4)
- Significant structural heart disease (left ventricular ejection fraction <50%, history or signs of coronary ischemia, suspicion or definitive diagnosis of cardiomyopathy, or moderate/severe valve regurgitation)
- Suspicion or definitive diagnosis of another (heritable) arrhythmia syndrome, e.g. Brugada syndrome, early repolarization syndrome or catecholaminergic polymorphic ventricular tachycardia
- Presence of a short (<350 ms) or prolonged (>480 ms) heart-rate corrected QT interval on the resting ECG at baseline
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 |
|---|---|---|
| FlecainideFlecainide monotherapy | Drug | Flecainide monotherapy |
| Flecainide + beta-blockerFlecainide + beta-blocker | Drug | Flecainide + beta-blocker |
Primary outcome
Ventricular ectopy burden
Time frame: 5 24-hour periods per treatment period
1 secondary outcome
Duration of longest ventricular tachycardia
Time frame: 5 24-hour periods per treatment period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
- Individual participant dataSharing planned: No
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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Flecainide and Flecainide + beta-blocker in people with Andersen Tawil Syndrome and Multifocal Ectopic Purkinje-related Premature Contractions, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
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 4 inclusion and 11 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: opening soon, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christian van der Werf, MD PhD (+31 020 566 9111, c.vanderwerf@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventricular ectopy burden (time frame: 5 24-hour periods per treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jan 2025.