Dilated CardiomyopathyPhase 2NCT06632834
Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
A Phase 2 study testing simvastatin therapy in people with Dilated Cardiomyopathy, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Brief Summary(Use lay language. Include a statement of the study hypothesis.): Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. Read more about this study
- Who is it for?
- Ages 0 to 99 years
- Conditions the study is for
- Dilated Cardiomyopathy
- What is being tested?
- simvastatin therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 1 siteTaiwan
- Study dates
- 15 Aug 2020to 19 Jan 2025
- Phase
- Phase 2
- 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 0 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients diagnosed as dilated cardiomyopathy, classified as NYHA functional class II or III and still have a low left ventricular ejection fraction (LVEF) (LVEF < 45% and the Z score of the LV end-diastolic diameter > 2.0) will be enrolled, if they have normal or high level of cholesterol and triglyceride and fulfill any of the following criteria:
- Patients who have already received anti-congestive medications for at least three months and still have poor LV function (LVEF < 45% and the Z score of the LV end-diastolic diameter > 2.0).
- Patients who have persistent or even worsening heart failure after one month of anti-congestive medications.
- Patients who have positive family history of dilated cardiomyopathy and have received anti-congestive medications for one month.
- Patients or their parents must sign an informed consent form.
Who cannot join
- Patients who fulfill any of the following criteria will be excluded from the trial:
- Patients who underwent prior cardiac surgery. Those who received DCM related surgery, such as mitral valve plasy, for longer than a year are not subject to this restriction.
- Patients who had active liver / renal dysfunction.
- Concomitant use with gemfibrozil, cyclosporine, danazol, strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, posaconazole, telaprevir, telithromycin, voriconazole), or cobicistat-containing products
- Patients who are pregnant or plan to pregnancy in the period of study.
- Patients who are intolerance to simvastatin therapy.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei County, Zhongzheng District, 100
Wei-Chieh Tseng, MD, 0972652584, littlecardiologist@gmail.com
About this study
Official title: Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study, and Phenotype-genotype Correlation
Brief Summary(Use lay language. Include a statement of the study hypothesis.):
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. Investigators had conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. Investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility in the human induced pluripotent stem cell lines derived from a DCM proband and the proband's father. The mutant mouse consequently confirmed the beneficial effects. The initial experience in the proband is promising. This clinical trial is to find out if simvastatin will benefit the cardiac function of DCM patients.
Read the detailed description
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. About half of patients die or require heart transplantation within 5 years of diagnosis. The survival advantage from transplantation is limited, particularly in DCM infants.The medical therapy for DCM with heart failure includes anti-congestive medications and antiplatelet therapy. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. Investigators have conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. Investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility in the human induced pluripotent stem cell lines derived from a DCM proband and the proband's father. The mutant mouse consequently confirmed the beneficial effects. The initial experience in the proband is promising. The proband was diagnosed as DCM with severe heart failure during infancy. Family screening identified that the proband's father had dilated left ventricle (LV) and low LV ejection fraction (LVEF). Genetic examination of this DCM family revealed that the proband and the proband's father had heterogeneous missense mutation. About 2 years after the disease onset, participants growth was slow, the LVEF remained poor and the NT-pro BNP level was high under aggressive anti-congestive medications. Because of the beneficial effects of simvastatin from in vitro study and in vivo animal study, off-label use of simvastatin was initiated after obtaining the parents' agreement. Participants general condition and cardiac condition 4 years after the disease onset and 1.5 years after the simvastatin therapy improved without adverse effects. The LVEF increased from 17.5% to 39.2% and the NT-pro BNP level dropped from 1200 to 363 pg/ml. Simvastatin is effective in lowing LDL and cholesterol, thereby to improve the outcome of patients with coronary arterial disease, familiar hypercholesterolemia, etc. For children, though the dosage range and the indication remain unclear, it had been used in children with various diseases. Simvastatin had been given in a small cohort of adult DCM. Patients treated with simvastatin had a lower New York Heart Association functional class compared with those receiving placebo. The LVEF also improved in the simvastatin group. This clinical trial is to find out if simvastatin will benefit the cardiac function of DCM patients.
- Conditions
- Dilated Cardiomyopathy
- Being tested
- simvastatin therapy
- Keywords
- cardiomyopathy
- Medical subject headings
- Cardiomyopathy, Dilated, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
simvastatin therapyDrug
Simvastatin should be administered initially with the dose of 10 mg once daily for adult and 0.25 mg/Kg once daily for children. Dose of simvastatin will be increased to the dose of 20 mg once daily for adult and 0.5 mg/Kg once daily for children after the check at 3 months without adverse effects.
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin | Experimental | Simvastatin added with baseline anti-congestive medication in dilated cardiomyopathy patient. Receives: Drug: simvastatin therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in left ventricular ejection fraction and NT-pro BNP (biomarker for left ventricular function))
The changes from baseline to completion of the study in the echocardiographic parameters for LV function, the left ventricular ejection fraction.The changes in the biomarker for left ventricular function(pro-BNP) from baseline to completion of the study will be evaluated by a repeated assessment.
Preliminary data
Our preliminary data from pediatric DCM population showed that the 1-year-, and 5-year transplant-free survival after diagnosis were 61.3%, and 45.2%. None of infant patients received heart transplant and the waitlist mortality were high.
The proband patient was diagnosed as DCM at the age of 6 months. Two years after the diagnosis, participants cardiac condition was stagnant. Because of the beneficial effects of simvastatin from in vitro and in vivo animal study, off-label use was initiated after obtaining the parents' agreement. Participants LVEF increased from 17.5% to 42% and the NT-pro BNP level dropped from 1200 to 217 pg/ml.
Measured: 2 years
Secondary outcomes (1)
Progression free survival and overall survival
Progression-free survival is measured from the date of starting treatment to the date of disease progression (increase of LVEF for 6% or prior pro-BNP for 10%), to death without progression, or to the last follow-up without progression.Overall survival is measured from the date of starting treatment in the study to the date of death, or to the last follow-up without death.Safety variables include toxicity grading, adverse events, and laboratory values.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2024
- Study start15 Aug 2020
- Primary completion19 Jan 2025 (estimated)
- Study completion19 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dilated CardiomyopathyStudies of the same condition, open and under way.
- More trials run by National Taiwan 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 1. A retrospective and prospective cohort study will be conducted. Patients diagnosed with DCM below the age of 35 years from 1990 to 2019 will be enrolled. Medical records will be reviewed. A 3-stage genetic testing will be performed after informed consent. 2. An open-labeled, exploratory study of simvastatin on the cardiac function of DCM patients will be conducted.
- Masking
- None (open label)
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wei-Chieh Tseng, MD, Principal investigator, Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06632834
- Sponsor's protocol ID
- 201912067MINB
- Status last verified
- Oct 2024
- First submitted
- 7 Oct 2024
- Last updated
- 16 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study, and Phenotype-genotype Correlation
- ClinicalTrials.gov ID
- NCT06632834
- Acronym / sponsor ID
- 201912067MINB
- Conditions
- Dilated Cardiomyopathy
- Keywords
- cardiomyopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 15 Aug 2020 (actual)
- Primary completion
- 19 Jan 2025 (estimated)
- Study completion
- 19 Jan 2025 (estimated)
- First posted
- 9 Oct 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.
Brief Summary(Use lay language. Include a statement of the study hypothesis.):
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. Investigators had conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. Investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility in the human induced pluripotent stem cell lines derived from a DCM proband and the proband's father. The mutant mouse consequently confirmed the beneficial effects. The initial experience in the proband is promising. This clinical trial is to find out if simvastatin will benefit the cardiac function of DCM patients.
Detailed description
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. About half of patients die or require heart transplantation within 5 years of diagnosis. The survival advantage from transplantation is limited, particularly in DCM infants.The medical therapy for DCM with heart failure includes anti-congestive medications and antiplatelet therapy. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. Investigators have conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. Investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility in the human induced pluripotent stem cell lines derived from a DCM proband and the proband's father. The mutant mouse consequently confirmed the beneficial effects. The initial experience in the proband is promising. The proband was diagnosed as DCM with severe heart failure during infancy. Family screening identified that the proband's father had dilated left ventricle (LV) and low LV ejection fraction (LVEF). Genetic examination of this DCM family revealed that the proband and the proband's father had heterogeneous missense mutation. About 2 years after the disease onset, participants growth was slow, the LVEF remained poor and the NT-pro BNP level was high under aggressive anti-congestive medications. Because of the beneficial effects of simvastatin from in vitro study and in vivo animal study, off-label use of simvastatin was initiated after obtaining the parents' agreement. Participants general condition and cardiac condition 4 years after the disease onset and 1.5 years after the simvastatin therapy improved without adverse effects. The LVEF increased from 17.5% to 39.2% and the NT-pro BNP level dropped from 1200 to 363 pg/ml. Simvastatin is effective in lowing LDL and cholesterol, thereby to improve the outcome of patients with coronary arterial disease, familiar hypercholesterolemia, etc. For children, though the dosage range and the indication remain unclear, it had been used in children with various diseases. Simvastatin had been given in a small cohort of adult DCM. Patients treated with simvastatin had a lower New York Heart Association functional class compared with those receiving placebo. The LVEF also improved in the simvastatin group. This clinical trial is to find out if simvastatin will benefit the cardiac function of DCM patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 1. A retrospective and prospective cohort study will be conducted. Patients diagnosed with DCM below the age of 35 years from 1990 to 2019 will be enrolled. Medical records will be reviewed. A 3-stage genetic testing will be performed after informed consent. 2. An open-labeled, exploratory study of simvastatin on the cardiac function of DCM patients will be conducted.
| Arm | Type | Receives |
|---|---|---|
| Simvastatin | Experimental | Drug: simvastatin therapySimvastatin added with baseline anti-congestive medication in dilated cardiomyopathy patient. |
Who may qualify
- Ages
- 0 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients diagnosed as dilated cardiomyopathy, classified as NYHA functional class II or III and still have a low left ventricular ejection fraction (LVEF) (LVEF < 45% and the Z score of the LV end-diastolic diameter > 2.0) will be enrolled, if they have normal or high level of cholesterol and triglyceride and fulfill any of the following criteria:
- Patients who have already received anti-congestive medications for at least three months and still have poor LV function (LVEF < 45% and the Z score of the LV end-diastolic diameter > 2.0).
- Patients who have persistent or even worsening heart failure after one month of anti-congestive medications.
- Patients who have positive family history of dilated cardiomyopathy and have received anti-congestive medications for one month.
- Patients or their parents must sign an informed consent form.
Key exclusion criteria (6 listed)
- Patients who underwent prior cardiac surgery. Those who received DCM related surgery, such as mitral valve plasy, for longer than a year are not subject to this restriction.
- Patients who had active liver / renal dysfunction.
- Concomitant use with gemfibrozil, cyclosporine, danazol, strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, posaconazole, telaprevir, telithromycin, voriconazole), or cobicistat-containing products
- Patients who are pregnant or plan to pregnancy in the period of study.
- Patients who are intolerance to simvastatin therapy.
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 |
|---|---|---|
| simvastatin therapySimvastatin should be administered initially with the dose of 10 mg once daily for adult and 0.25 mg/Kg once daily for children. Dose of simvastatin will be increased to the dose of 20 mg once daily for adult and 0.5 mg/Kg once daily for children after the check at 3 months without adverse effects. | Drug | Simvastatin |
Primary outcome
Improvement in left ventricular ejection fraction and NT-pro BNP (biomarker for left ventricular function))
Time frame: 2 years
The changes from baseline to completion of the study in the echocardiographic parameters for LV function, the left ventricular ejection fraction.The changes in the biomarker for left ventricular function(pro-BNP) from baseline to completion of the study will be evaluated by a repeated assessment. Preliminary data Our preliminary data from pediatric DCM population showed that the 1-year-, and 5-year transplant-free survival after diagnosis were 61.3%, and 45.2%. None of infant patients received heart transplant and the waitlist mortality were high. The proband patient was diagnosed as DCM at the age of 6 months. Two years after the diagnosis, participants cardiac condition was stagnant. Because of the beneficial effects of simvastatin from in vitro and in vivo animal study, off-label use was initiated after obtaining the parents' agreement. Participants LVEF increased from 17.5% to 42% and the NT-pro BNP level dropped from 1200 to 217 pg/ml.
1 secondary outcome
Progression free survival and overall survival
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
Related trials for Dilated Cardiomyopathy
RecruitingPhase 2/3
A Study of the Efficacy and Safety of Danicamtiv in Participants With Symptomatic Genetic and Familial Dilated Cardiomyopathy
Symptomatic Genetic Dilated Cardiomyopathy
RecruitingPhase 3
A Study of the Long-term Safety and Efficacy of Danicamtiv in Adults With Symptomatic Genetic and Familial Dilated Cardiomyopathy
Symptomatic Genetic Dilated Cardiomyopathy (DCM)
RecruitingObservational study
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
Coronary Artery Disease, Myocarditis
RecruitingPhase 1/2
An AAV Gene Therapy Trial of AFTX-201 in Adults With BAG3-Associated Dilated Cardiomyopathy (DCM)
Dilated Cardiomyopathy (DCM), BAG3 Mutation Associated Dilated Cardiomyopathy
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
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.
Wei-Chieh Tseng, MD principal investigator
Principal Investigator
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 simvastatin therapy in people with Dilated Cardiomyopathy, run by National Taiwan University Hospital at 1 site in Taiwan.
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 6 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 16 Oct 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 Taiwan. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wei-Chieh Tseng (0972652584, littlecardiologist@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in left ventricular ejection fraction and NT-pro BNP (biomarker for left ventricular function)) (time frame: 2 years). 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 16 Oct 2024.