Ignite Creation Date:
2025-12-25 @ 2:32 AM
Ignite Modification Date:
2025-12-26 @ 1:07 AM
Study NCT ID:
NCT06632834
Status:
RECRUITING
Last Update Posted:
2024-10-16
First Post:
2024-10-07
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
Sponsor:
National Taiwan University Hospital
Organization:
Study Overview
Official Title:
Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study, and Phenotype-genotype Correlation
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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. 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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: