Muscular Dystrophy, DuchennePhase 3MeDMDNCT05066633
The Efficacy and Safety of Metoprolol as add-on Treatment to Standard of Care in Preventing Cardiomyopathy in Patients With DMD
A Phase 3 study testing Metoprolol Succinate in people with Muscular Dystrophy, Duchenne, run by Medical University of Gdansk at 1 site in Poland.
Trial summary
The study includes 150 patients with DMD diagnosis confirmed by genetic testing, 8-16 years old (≥8 and <17) at the study entry with a follow-up of up to 5 years. Random enrollment of a patient to one of two groups (intervention or control) takes place after pre-screening and screening stage starts the first phase of… Read more about this study
- Who is it for?
- Ages 8 to 17 years, men only
- Conditions the study is for
- Muscular Dystrophy, Duchenne
- What is being tested?
- Metoprolol Succinate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 sitePoland
- Study dates
- 18 Aug 2021to 30 Jun 2026
- Phase
- Phase 3
- 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 8 to 17 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Subject's parent(s) or legal guardian(s) has (have) provided written informed consent, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to requirements (>16 years old)
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability to take oral medication and be willing to adhere to the study intervention regimen
- Subject has confirmed diagnosis of DMD, as defined as clinical picture consistent with typical DMD and: i) Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, or ii) Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame' or, iii) Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon)
- Taking ACEi treatment at minimum required doses for at least 30 days
Who cannot join
- Current or previous permanent use of any beta-blocker medication
- Treatment with another investigational drug or other intervention within 3 months prior to screening
- Clinically significant bradycardia at rest or by Holter ECG, based on age and sex adjusted normal values, atrioventricular block higher than first degree at rest, or second degree Wenckebach at night, pauses longer than 2.5 seconds
- Presence of pacemaker or ICD
- Clinical signs or symptoms of heart failure
- Left ventricular Ejection Fraction (LVEF) <57% (assessed by Teichholtz echocardiography)
- Inability to obtain adequate quality echocardiography images (necessary to monitor for primary endpoint and safety)
- Known allergic reactions to components of the IMPs
Trial locations and contacts
1 site in 1 country.
Poland1 site, 1 recruiting
- Recruiting
University Clinical Centre in Gdańsk, Clinic of Paediatric Cardiology and Congenital Heart Defects
Gdansk, Pomeranian Voivodeship, 80-211
Joanna Kwiatkowska, MD, PhD, 583492899 ext. +48, joanna.kwiatkowska@gumed.edu.pl
Joanna Kwiatkowska, MD, PhD
About this study
Official title: The Efficacy and Safety of Metoprolol as add-on Treatment to Standard of Care in Preventing Cardiomyopathy in Patients With Duchenne Muscular Dystrophy Aged 8-16 Years. A Randomized, Double-blind, Placebo-controlled Study
The study includes 150 patients with DMD diagnosis confirmed by genetic testing, 8-16 years old (≥8 and <17) at the study entry with a follow-up of up to 5 years. Random enrollment of a patient to one of two groups (intervention or control) takes place after pre-screening and screening stage starts the first phase of the trial. To be eligible for participation in the study, patients must receive standard of care cardiac therapy, which is an Angiotensin-converting-enzyme inhibitor (ACEi) for at least one-month prior to enrollment. A major part of the trial is equal for all patients - who will be receiving indistinguishable investigational medicinal products (IMPs), the drug metoprolol succinate or placebo. As a part of the clinical trial, diagnostic examinations evaluating progression of the disease, will be performed periodically. In addition, all patients will be monitored at home. Heart rate, blood pressure and patients' personal well-being will be controlled using telemedicine technologies. Additional visits in the research center will be provided if any adverse events occur. This model will be continued for 30 months from the enrollment of a first patient. After this period the first drug efficiency analysis will be performed. After that, the intervention may be continued or in case of negative impact of the intervention on patients' health and well-being, terminated with further patients monitoring.
Read the detailed description
Patients will be evaluated for inclusion during a Screening period of up to one year (possible to extend for another year if warranted). Written informed consent from the patient and/or parent/legal guardian and assent, if applicable, to participate in the study must be obtained prior to beginning any study-related procedures. Once eligibility is confirmed, patients will undergo Screening Assessments.
Two groups will receive either metoprolol succinate (Treatment 1 - Intervention) at a dose depending on the weight category as described below or matching placebo (Treatment 2 - Control) to maintain the study blinding, one per day for up to 60 months. All patients (both arms) will receive ACEi (e.g. perindopril, enarenal, lisinopril) or, if indicated, ARB (e.g. losartan) as a standard of care at an appropriate therapeutic dose (see below) through all the study duration. A total of approximately 150 subjects will be randomized into the study.
Subjects will be assessed for safety and tolerability, clinical efficacy, at scheduled visits throughout the study. Adverse events, including SAEs, and concomitant medications will be recorded throughout the study in eCRF record.
Access credentials for ePROP will be dispensed to the participant or his legal guardian when appropriate at the Enrolment Visit to record vital signs (HR and NIBP) and peak-flow-meter readings, AEs, changes to concomitant medications taken during the study, and any missed or incomplete doses of study medication.
Site study staff will contact the parent(s)/ legal guardian(s) by telephone at quarterly to ensure that the tablet dispensing is proceeding according to protocol and to address any questions the parent(s)/guardian(s) may have.
All subjects will periodically return to the clinical site for assessments according to the Visit Plan. The study is comprised of a Pre-screening, Screening-Enrolment-Randomization Double-Blind Treatment Period further subdivided into Phases.
Subjects will be enrolled into this study at the time written informed consent is given and randomized to treatment only after completion of all Pre-treatment Screening and Enrolment assessments.
Study drug dosing will occur at home on all days starting from Enrolment Visit until the Final Visit.
In the event that relevant clinical or laboratory parameters remain abnormal at the time of discharge from the study, the subject will be followed medically, as clinically indicated.
Any subject who prematurely discontinues the study should return to the study centre for scheduled assessments at the time of early withdrawal, whenever possible assuming the subject has not withdrawn consent.
- Conditions
- Muscular Dystrophy, Duchenne
- Being tested
- Metoprolol Succinate, Placebo
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metoprolol SuccinateDrug
Metoprolol Succinate will be in the form of tablets and will be administered orally once daily. The dose will depend on the patient's weight category. Subject should take their treatment at a consistent time each day to promote compliance. IMP will be up titrated. Every two weeks the patients will be given the higher dose of metoprolol succinate or placebo accordingly to scheme.
PlaceboDrug
Placebo will be in the form of identical tablets and will be administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Placebo comparator | Matching placebo will be supplied by the sponsor in child-proof bottles containing dividable tablets with the following dosage of 25mg of IMP and 100mg of IMP. The drug will be administered orally at singular daily doses ranging from 0.75 to 4.5 mg/kg over a Double-Blind Treatment Period (DBTP) of up to 60 months or less dependently on the time of enrolment. The Treatment Period will begin with up to 12-weeks long Up-titration Phase, during which the dose will be gradually escalated. If patient presents with signs and symptoms of intolerance the dose may be temporarily or permanently downgraded at the discretion of the clinician. The up titration ends with reaching maximal tolerated dose level or at a dose corresponding to 4.5 mg/kg. Receives: Drug: Placebo |
| Treatment Group | Experimental | Metoprolol succinate will be supplied by the sponsor in child-proof bottles containing dividable tablets with the following dosage of 25mg of IMP and 100mg of IMP. The drug will be administered orally at singular daily doses ranging from 0.75 to 4.5 mg/kg over a Double-Blind Treatment Period (DBTP) of up to 60 months or less dependently on the time of enrolment. The Treatment Period will begin with up to 12-weeks long Up-titration Phase, during which the dose will be gradually escalated. If patient presents with signs and symptoms of intolerance the dose may be temporarily or permanently downgraded at the discretion of the clinician. The up titration ends with reaching maximal tolerated dose level or at a dose corresponding to 4.5 mg/kg. Receives: Drug: Metoprolol Succinate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in left ventricular ejection fraction (LVEF %) by Teichholtz method (echocardiography), compared to baseline at Interim Analysis and Final Analysis.
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD delays the progression of LV function loss.
Measured: 24 months
Secondary outcomes (4)
DFS (the time to develop clinically evident heart failure)
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD delays progression of cardiomyopathy and heart failure
Measured: 24 months
Prevalence of patients with myocardial fibrosis assessed by LGE Cardiac magnetic resonance (CMR)
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD delays progression of LGE in CMR
Measured: 24 months
Prevalence of patients with sinus tachycardia based on resting HR (ECG) or defined as mean daily heart rate above 95th percentile for age and sex
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD prevents sinus tachycardia commonly seen in DMD patients
Measured: 24 months
The rate of AE and SAE
To assess the safety and tolerability of metoprolol succinate in children with DMD
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2021
- Study start18 Aug 2021
- Primary completion30 Jun 2023 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscular Dystrophy, DuchenneStudies of the same condition, open and under way.
- More trials run by Medical University of GdanskThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Gdansk
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05066633
- Sponsor's protocol ID
- NBK 154/1/2020
- Other IDs
- 2020-004901-29
- Acronym
- MeDMD
- Status last verified
- Sep 2021
- First submitted
- 23 Sep 2021
- Last updated
- 4 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- 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 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Metoprolol as add-on Treatment to Standard of Care in Preventing Cardiomyopathy in Patients With Duchenne Muscular Dystrophy Aged 8-16 Years. A Randomized, Double-blind, Placebo-controlled Study
- ClinicalTrials.gov ID
- NCT05066633
- Acronym / sponsor ID
- MeDMD / NBK 154/1/2020
- Conditions
- Muscular Dystrophy, Duchenne
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Medical University of GdanskUniversity, hospital or other
- Study start
- 18 Aug 2021 (actual)
- Primary completion
- 30 Jun 2023 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 4 Oct 2021 (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.
The study includes 150 patients with DMD diagnosis confirmed by genetic testing, 8-16 years old (≥8 and <17) at the study entry with a follow-up of up to 5 years. Random enrollment of a patient to one of two groups (intervention or control) takes place after pre-screening and screening stage starts the first phase of the trial. To be eligible for participation in the study, patients must receive standard of care cardiac therapy, which is an Angiotensin-converting-enzyme inhibitor (ACEi) for at least one-month prior to enrollment. A major part of the trial is equal for all patients - who will be receiving indistinguishable investigational medicinal products (IMPs), the drug metoprolol succinate or placebo. As a part of the clinical trial, diagnostic examinations evaluating progression of the disease, will be performed periodically. In addition, all patients will be monitored at home. Heart rate, blood pressure and patients' personal well-being will be controlled using telemedicine technologies. Additional visits in the research center will be provided if any adverse events occur. This model will be continued for 30 months from the enrollment of a first patient. After this period the first drug efficiency analysis will be performed. After that, the intervention may be continued or in case of negative impact of the intervention on patients' health and well-being, terminated with further patients monitoring.
Detailed description
Patients will be evaluated for inclusion during a Screening period of up to one year (possible to extend for another year if warranted). Written informed consent from the patient and/or parent/legal guardian and assent, if applicable, to participate in the study must be obtained prior to beginning any study-related procedures. Once eligibility is confirmed, patients will undergo Screening Assessments.
Two groups will receive either metoprolol succinate (Treatment 1 - Intervention) at a dose depending on the weight category as described below or matching placebo (Treatment 2 - Control) to maintain the study blinding, one per day for up to 60 months. All patients (both arms) will receive ACEi (e.g. perindopril, enarenal, lisinopril) or, if indicated, ARB (e.g. losartan) as a standard of care at an appropriate therapeutic dose (see below) through all the study duration. A total of approximately 150 subjects will be randomized into the study.
Subjects will be assessed for safety and tolerability, clinical efficacy, at scheduled visits throughout the study. Adverse events, including SAEs, and concomitant medications will be recorded throughout the study in eCRF record.
Access credentials for ePROP will be dispensed to the participant or his legal guardian when appropriate at the Enrolment Visit to record vital signs (HR and NIBP) and peak-flow-meter readings, AEs, changes to concomitant medications taken during the study, and any missed or incomplete doses of study medication.
Site study staff will contact the parent(s)/ legal guardian(s) by telephone at quarterly to ensure that the tablet dispensing is proceeding according to protocol and to address any questions the parent(s)/guardian(s) may have.
All subjects will periodically return to the clinical site for assessments according to the Visit Plan. The study is comprised of a Pre-screening, Screening-Enrolment-Randomization Double-Blind Treatment Period further subdivided into Phases.
Subjects will be enrolled into this study at the time written informed consent is given and randomized to treatment only after completion of all Pre-treatment Screening and Enrolment assessments.
Study drug dosing will occur at home on all days starting from Enrolment Visit until the Final Visit.
In the event that relevant clinical or laboratory parameters remain abnormal at the time of discharge from the study, the subject will be followed medically, as clinically indicated.
Any subject who prematurely discontinues the study should return to the study centre for scheduled assessments at the time of early withdrawal, whenever possible assuming the subject has not withdrawn consent.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Placebo comparator | Drug: PlaceboMatching placebo will be supplied by the sponsor in child-proof bottles containing dividable tablets with the following dosage of 25mg of IMP and 100mg of IMP. The drug will be administered orally at singular daily doses ranging from 0.75 to 4.5 mg/kg over a Double-Blind Treatment Period (DBTP) of up to 60 months or less dependently on the time of enrolment. The Treatment Period will begin with up to 12-weeks long Up-titration Phase, during which the dose will be gradually escalated. If patient presents with signs and symptoms of intolerance the dose may be temporarily or permanently downgraded at the discretion of the clinician. The up titration ends with reaching maximal tolerated dose level or at a dose corresponding to 4.5 mg/kg. |
| Treatment Group | Experimental | Drug: Metoprolol SuccinateMetoprolol succinate will be supplied by the sponsor in child-proof bottles containing dividable tablets with the following dosage of 25mg of IMP and 100mg of IMP. The drug will be administered orally at singular daily doses ranging from 0.75 to 4.5 mg/kg over a Double-Blind Treatment Period (DBTP) of up to 60 months or less dependently on the time of enrolment. The Treatment Period will begin with up to 12-weeks long Up-titration Phase, during which the dose will be gradually escalated. If patient presents with signs and symptoms of intolerance the dose may be temporarily or permanently downgraded at the discretion of the clinician. The up titration ends with reaching maximal tolerated dose level or at a dose corresponding to 4.5 mg/kg. |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Subject's parent(s) or legal guardian(s) has (have) provided written informed consent, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to requirements (>16 years old)
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability to take oral medication and be willing to adhere to the study intervention regimen
- Subject has confirmed diagnosis of DMD, as defined as clinical picture consistent with typical DMD and: i) Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, or ii) Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame' or, iii) Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon)
- Taking ACEi treatment at minimum required doses for at least 30 days
Key exclusion criteria (8 listed)
- Current or previous permanent use of any beta-blocker medication
- Treatment with another investigational drug or other intervention within 3 months prior to screening
- Clinically significant bradycardia at rest or by Holter ECG, based on age and sex adjusted normal values, atrioventricular block higher than first degree at rest, or second degree Wenckebach at night, pauses longer than 2.5 seconds
- Presence of pacemaker or ICD
- Clinical signs or symptoms of heart failure
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 |
|---|---|---|
| Metoprolol SuccinateMetoprolol Succinate will be in the form of tablets and will be administered orally once daily. The dose will depend on the patient's weight category. Subject should take their treatment at a consistent time each day to promote compliance. IMP will be up titrated. Every two weeks the patients will be given the higher dose of metoprolol succinate or placebo accordingly to scheme. | Drug | Treatment Group |
| PlaceboPlacebo will be in the form of identical tablets and will be administered orally once daily. | Drug | Control Group |
Primary outcome
Change in left ventricular ejection fraction (LVEF %) by Teichholtz method (echocardiography), compared to baseline at Interim Analysis and Final Analysis.
Time frame: 24 months
To evaluate whether metoprolol succinate in addition to standard of care treatment compared to placebo in children with DMD delays the progression of LV function loss.
4 secondary outcomes
DFS (the time to develop clinically evident heart failure)
Time frame: 24 months
Prevalence of patients with myocardial fibrosis assessed by LGE Cardiac magnetic resonance (CMR)
Time frame: 24 months
Prevalence of patients with sinus tachycardia based on resting HR (ECG) or defined as mean daily heart rate above 95th percentile for age and sex
Time frame: 24 months
The rate of AE and SAE
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
- Official websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Muscular Dystrophy, Duchenne
RecruitingEarly Phase 1
Safety and Dystrophin Expression of SPOT-03 in Duchenne Muscular Dystrophy (DMD) Patients
Duchenne Muscular Dystrophy (DMD)
RecruitingPhase 2
Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
Not yet recruitingPhase 2
A Phase 2 Trial to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tegacorat in Male Participants 4 to <7 Years of Age With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy (DMD)
Not yet recruitingObservational study
Multimodal Study About Absence of Dp140 in Becker Muscular Dystrophy: Brain-muscle Imaging, Cognition and Muscle Function
Becker Muscular Dystrophy
Enrolling by invitationObservational study
A Long-term Observational Study Evaluating Eteplirsen, Golodirsen, or Casimersen in Routine Clinical Practice
Duchenne Muscular Dystrophy
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metoprolol Succinate in people with Muscular Dystrophy, Duchenne, run by Medical University of Gdansk at 1 site in Poland.
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 8 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 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Joanna Kwiatkowska, MD, PhD (58349 2899 ext. +48, joanna.kwiatkowska@gumed.edu.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in left ventricular ejection fraction (LVEF %) by Teichholtz method (echocardiography), compared to baseline at Interim Analysis and Final Analysis. (time frame: 24 months). 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 4 Oct 2021.