Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation

NCT06632834 | Recruiting Phase 2 DMC

• 1 other identifier: 201912067MINB
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

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.

Conditions

Dilated Cardiomyopathy

Keywords

cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (1)

• Progression free survival and overall survival

  2 years

Study Arms (1)

Simvastatin

EXPERIMENTAL

Simvastatin added with baseline anti-congestive medication in dilated cardiomyopathy patient.

Drug: simvastatin therapy

Interventions

simvastatin therapy DRUG

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.

Simvastatin

Eligibility Criteria

• Age: 0 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei County, Zhongzheng District, 100, Taiwan

RECRUITING

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Cardiomyopathies

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Wei-Chieh Tseng, MD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei-Chieh Tseng

CONTACT

0972652584; littlecardiologist@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 9, 2024
• Study Start: August 15, 2020
• Primary Completion: January 19, 2025
• Study Completion: January 19, 2025
• Last Updated: October 16, 2024

Record last verified: 2024-10

Locations

TW (1)