Beta-blocker Administration for Cardiomyocyte Division

Weill Cornell Medicine (WCM)

Status and phase: Enrolling; Phase 1

Conditions: Tetralogy of Fallot; Double Outlet Right Ventricle

Treatments: Drug: Placebo; Procedure: Physical Exam; Procedure: Echocardiogram; Other: Urine Collection; Other: N-thymidine; Procedure: Cardiac MRI (CMR); Drug: Propranolol Hydrochloride; Other: Specimen Collection

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04713657

23-12026881

R01HL155597 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Heart failure is a common long-term complication in patients with congenital heart disease (CHD). Medical treatments to promote regeneration of new healthy heart muscle cells have the potential to provide new heart failure treatments for these patients. The development of such therapies is limited by the poor understanding of the ways in which heart muscles grow after birth. Investigators have learned that humans without heart disease generate new heart muscles cells up to the age of 20 years old and that this is decreased in patients with congenital heart disease like Tetralogy of Fallot. Investigators are trying to determine if treatment with a medicine called Propranolol can increase heart muscle cell proliferation and, with that, normalize heart growth. Investigators will examine discarded heart muscle tissue that is obtained during surgery for the presence of new heart muscle cells. Propranolol is approved by the Food and Drug Administration (FDA) to treat a certain kind of benign tumor in infants (hemangioma), but it is not currently approved by the FDA to increase heart muscle growth.

Enrollment: 40 estimated patients

Sex: All

Ages: 30 to 60 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female infants < 60 days of age with a diagnosis of tetralogy of Fallot (ToF) with pulmonary stenosis (PS) or double outlet right ventricle (DORV), tetralogy type by echocardiogram, who weigh greater than 2 kg at the time of consent and are tolerating enteral feeds.
• DORV variant

Exclusion criteria

• congenital atrio-ventricular block on EKG (PR interval > 120 ms),
• concomitant medication administration that interacts with propranolol,
• patient family is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason,
• gestation age < 35 weeks,
• infants of diabetic mothers, asthma or underlying respiratory disease,
• presence of metal implants in infants.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups, including a placebo group

Propranolol

Active Comparator group

Description:

The target dose of Propranolol hydrochloride for this study target dose for this study will be 4 mg/kg/day divided in 4 doses. The concentration of propranolol solution is 20 mg/5 mL. Additionally, labeled syringes will be provided to families for accurate weight-based dosing. Treatment with propranolol will begin at 1 month of age and continue until 4 months of age or 24hrs prior to surgical repair, whichever comes first.

Treatment:

Other: Specimen Collection

Drug: Propranolol Hydrochloride

Procedure: Cardiac MRI (CMR)

Other: N-thymidine

Procedure: Echocardiogram

Other: Urine Collection

Procedure: Physical Exam

Placebo

Placebo Comparator group

Description:

Placebo will be given in a volume that corresponds to the patient's weight. Additionally, labeled syringes will be provided to families for accurate weight-based dosing. Treatment with placebo will begin at 1 month of age and continue until 4 months of age or 24hrs prior to surgical repair, whichever comes first. There is no current standard of care for pharmacologic therapy for infants with Tetralogy of Fallot (ToF). As such, there are no alternative treatments, and the placebo group is standard of care.

Treatment:

Other: Specimen Collection

Procedure: Cardiac MRI (CMR)

Other: N-thymidine

Procedure: Echocardiogram

Other: Urine Collection

Procedure: Physical Exam

Drug: Placebo