CardiomegalyPhase 2MEKinRASNCT06555237
MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies
A Phase 2 study testing Trametinib tablet and Standard therapy in people with Cardiomegaly and Noonan Syndrome, run by Medical University of Warsaw at 1 site in Poland.
Trial summary
The goal of this study is to evaluate the effectiveness of trametinib treatment in patients with Hyperthropic cardiomyopathy and a genetic mutation in the RAS/MAPK pathway. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Cardiomegaly, Noonan Syndrome
- What is being tested?
- Trametinib tablet and Standard therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 sitePoland
- Study dates
- 1 Aug 2024to 1 Dec 2026
- 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 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- patient with diagnosed RASopathy
- patient with diagnosed hypertrophic cardiomyopathy
- signed innform consent
Who cannot join
- contraindications to treatment with propranolol (drug hypersensitivity, atrioventricular block, severe bradycardia) disopyramide (drug hypersensitivity, WPW syndrome, atrioventricular block, QT prolongation) trametinib (drug hypersensitivity)
- lack of consent of the child's guardians to participate in the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Poland1 site, 1 recruiting
- Recruiting
Department of Paediatrics, The Medical University of Warsaw, Poland
Warsaw, 02-091
Maciej Kołodziej, MD, 223179535, maciek.kolodziej@gmail.com
Halszka Kamińska, MD, 22-317-9444, halszka.kaminska@wum.edu.pl
About this study
Official title: MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies (MEKinRAS) - Randomized Controlled Trial
The goal of this study is to evaluate the effectiveness of trametinib treatment in patients with Hyperthropic cardiomyopathy and a genetic mutation in the RAS/MAPK pathway.
Read the detailed description
Introduction RASopathies are a group of genetic diseases caused by mutations in the mitogen-activated kinase (RAS-MAPK) pathway. These mutations affect many processes and are the cause of numerous genetic syndromes (including Noonan syndrome) in the course of which severe hypertrophic cardiomyopathy (HCM) develops. MEK kinase inhibitors are used to treat cancers with mutations in the RAS-MAPK pathway in adults. So far, single cases of HCM treatment in patients with RASopathies have been described, with rapid improvement in both laboratory and echocardiographic parameters and regression of myocardial hypertrophy. Due to the described effectiveness, it is reasonable to verify these effects in a well-designed randomized study on a large group of patients.
Objective To evaluate the effectiveness of trametinib treatment in patients with HCM and a genetic mutation in the RAS/MAPK pathway.
Methodology
Randomized, open-label study. The study will include patients aged 0 to 18 with:
- mutation in the RAS/MAPK pathway confirmed by genetic tests
- HCM diagnosed by echocardiography
In the first phase of the study (3 months), patients will be randomly assigned to one of two groups:
- the intervention group will receive trametinib and standard treatment (beta-blocker and disopyramide)
- the control group will receive only standard treatment. Once this phase is complete, patients will be assessed. If higher effectiveness is demonstrated in the intervention group, in the second phase of the study, patients in the intervention group will continue their current treatment and patients in the control group will receive trametinib treatment. Each group will receive trametinib for 12 months.
Importance of the study The study results will provide grounds for routine introduction of MEK kinase inhibitors for the treatment of patients with HCM due to RASopathy. If effectiveness is demonstrated, this group will gain a simple, non-invasive and causal treatment option.
- Conditions
- Cardiomegaly, Noonan Syndrome
- Being tested
- Trametinib tablet, Standard therapy
- Keywords
- Noonan syndrome, MEK kinase, RASOpathies, Children, Cardiomyopathy
- Medical subject headings
- Cardiomegaly, Noonan Syndrome, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trametinib tabletDrug
Trametynib orally once daily in 0,025mg/kg dose
Standard therapyDrug
Disopiramide and Beta blockers orally
| Study group | Role | What they receive |
|---|---|---|
| Trametynib | Experimental | Trametynib in 0,025mg/kg dose orally once daily Receives: Drug: Trametinib tablet |
| Standard therapy | Active comparator | Disopiramide and Beta-blocker orally Receives: Drug: Standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effectiveness of the trametynib treatment on cardiac hyperthropy
Reduction of cardiac hypertrophy and/or LVOTO at 6 and 12 months of treatment and at 3 months of follow-up after treatment discontinuation using echocardiographic examination.
Measured: 1 year
Effectiveness of the trametynib treatment on laboratory enzymes levels
Decrease in cardiac enzyme levels (NT-pro-BNP and high-sensitivity troponin I) determined in the 6th and 12th month of treatment and in the 3rd month of observation after its discontinuation.
Measured: 1 year
Secondary outcomes (2)
MEK kinase activity
Assessment of MEK kinase activity before treatment and after 6 months of its duration, in the patients' blood samples
Measured: 6 months
Effectivness of the trametynib treatment assessed in the cardia magnetic resonance
reduction of cardiac hypertrophy in magnetic resonance imaging in the age group of 7-18 years not requiring general anesthesia (comparison of results before inclusion in the study, after 12 months of trametinib treatment and after the end of follow-up after its discontinuation)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2024
- Study start1 Aug 2024
- Primary completion1 Aug 2026 (estimated)
- Study completion1 Dec 2026 (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 CardiomegalyStudies of the same condition, open and under way.
- More trials run by Medical University of WarsawThe 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
- Parallel groups
- Model description
- Randomized control trial
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Warsaw
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- MAciej Kołodziej, MD, Principal investigator, Medical University of Warsaw
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06555237
- Sponsor's protocol ID
- KB/16/2024
- Acronym
- MEKinRAS
- Status last verified
- Aug 2024
- First submitted
- 12 Aug 2024
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
De Brouchoven I, Lorand J, Bofferding L, Sorlin A, Van Damme A, Danhaive O. Trametinib as a targeted treatment in cardiac and lymphatic presentations of Noonan syndrome. Front Pediatr. 2025 Feb 18;13:1475143. doi: 10.3389/fped.2025.1475143. eCollection 2025.
PubMed 40041314
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies (MEKinRAS) - Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06555237
- Acronym / sponsor ID
- MEKinRAS / KB/16/2024
- Conditions
- Cardiomegaly, Noonan Syndrome
- Keywords
- Noonan syndrome, MEK kinase, RASOpathies, Children, Cardiomyopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Medical University of WarsawUniversity, hospital or other
- Study start
- 1 Aug 2024 (actual)
- Primary completion
- 1 Aug 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 15 Aug 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.
The goal of this study is to evaluate the effectiveness of trametinib treatment in patients with Hyperthropic cardiomyopathy and a genetic mutation in the RAS/MAPK pathway.
Detailed description
Introduction RASopathies are a group of genetic diseases caused by mutations in the mitogen-activated kinase (RAS-MAPK) pathway. These mutations affect many processes and are the cause of numerous genetic syndromes (including Noonan syndrome) in the course of which severe hypertrophic cardiomyopathy (HCM) develops. MEK kinase inhibitors are used to treat cancers with mutations in the RAS-MAPK pathway in adults. So far, single cases of HCM treatment in patients with RASopathies have been described, with rapid improvement in both laboratory and echocardiographic parameters and regression of myocardial hypertrophy. Due to the described effectiveness, it is reasonable to verify these effects in a well-designed randomized study on a large group of patients.
Objective To evaluate the effectiveness of trametinib treatment in patients with HCM and a genetic mutation in the RAS/MAPK pathway.
Methodology
Randomized, open-label study. The study will include patients aged 0 to 18 with:
- mutation in the RAS/MAPK pathway confirmed by genetic tests
- HCM diagnosed by echocardiography
In the first phase of the study (3 months), patients will be randomly assigned to one of two groups:
- the intervention group will receive trametinib and standard treatment (beta-blocker and disopyramide)
- the control group will receive only standard treatment. Once this phase is complete, patients will be assessed. If higher effectiveness is demonstrated in the intervention group, in the second phase of the study, patients in the intervention group will continue their current treatment and patients in the control group will receive trametinib treatment. Each group will receive trametinib for 12 months.
Importance of the study The study results will provide grounds for routine introduction of MEK kinase inhibitors for the treatment of patients with HCM due to RASopathy. If effectiveness is demonstrated, this group will gain a simple, non-invasive and causal treatment option.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized control trial
| Arm | Type | Receives |
|---|---|---|
| Trametynib | Experimental | Drug: Trametinib tabletTrametynib in 0,025mg/kg dose orally once daily |
| Standard therapy | Active comparator | Drug: Standard therapyDisopiramide and Beta-blocker orally |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- patient with diagnosed RASopathy
- patient with diagnosed hypertrophic cardiomyopathy
- signed innform consent
Key exclusion criteria (2 listed)
- contraindications to treatment with propranolol (drug hypersensitivity, atrioventricular block, severe bradycardia) disopyramide (drug hypersensitivity, WPW syndrome, atrioventricular block, QT prolongation) trametinib (drug hypersensitivity)
- lack of consent of the child's guardians to participate in the study
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 |
|---|---|---|
| Trametinib tabletTrametynib orally once daily in 0,025mg/kg dose | Drug | Trametynib |
| Standard therapyDisopiramide and Beta blockers orally | Drug | Standard therapy |
Primary outcome
Effectiveness of the trametynib treatment on cardiac hyperthropy
Time frame: 1 year
Reduction of cardiac hypertrophy and/or LVOTO at 6 and 12 months of treatment and at 3 months of follow-up after treatment discontinuation using echocardiographic examination.
Effectiveness of the trametynib treatment on laboratory enzymes levels
Time frame: 1 year
Decrease in cardiac enzyme levels (NT-pro-BNP and high-sensitivity troponin I) determined in the 6th and 12th month of treatment and in the 3rd month of observation after its discontinuation.
2 secondary outcomes
MEK kinase activity
Time frame: 6 months
Effectivness of the trametynib treatment assessed in the cardia magnetic resonance
Time frame: 1 year
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 15 Aug 2024.
- Derived from this study: PubMed 40041314De Brouchoven I, Lorand J, Bofferding L, Sorlin A, Van Damme A, Danhaive O. Trametinib as a targeted treatment in cardiac and lymphatic presentations of Noonan syndrome. Front Pediatr. 2025 Feb 18;13:1475143. doi: 10.3389/fped.2025.1475143. eCollection 2025.
- Individual participant dataSharing planned: Undecided
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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.
MAciej Kołodziej, MD principal investigator
Medical University of Warsaw
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trametinib tablet and Standard therapy in people with Cardiomegaly and Noonan Syndrome, run by Medical University of Warsaw 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 3 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 15 Aug 2024. 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. 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 Maciej Kołodziej, MD (22-317-95-37, maciej.kolodziej@wum.edu.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness of the trametynib treatment on cardiac hyperthropy (time frame: 1 year). The study lists 2 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 NCT06555237, 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 15 Aug 2024.