Clinical trial NCT04713657: Beta-blocker Administration for Cardiomyocyte Division
Official title: Mechanistic Clinical Trial of Beta-Blocker Administration For Reactivating Cardiomyocyte Division In Tetralogy of Fallot
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Tetralogy of Fallot
Double Outlet Right Ventricle
Keywords: Tetralogy of Fallot
Double Outlet Right Ventricle
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-01-19
Enrollment: 40
Sex: ALL
Minimum age (years): 30
Maximum age (years): 44
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blinded, placebo-controlled (1:1) randomized, single-center trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Male and female infants \< 45 days of age with a diagnosis of tetralogy of Fallot with pulmonary stenosis or double outlet right ventricle, 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.

Primary outcomes:
measure: Cardiomyocyte Division
timeFrame: At the time of complete surgical repair, at approximately 3-9 months old, it is expected that a piece of RV myocardium will be resected. This tissue will be collected and analyzed using a multiple isotope mass spectrometer.
Secondary outcomes:
measure: Hypertrophy as assessed by echocardiography
timeFrame: At 1 month and at time of surgery
measure: Hypertrophy as assessed by Cardiac MR
timeFrame: At 1 month and at time of surgery
measure: Hypertrophy assessed by microscopy
timeFrame: At time of Surgery
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Pittsburgh
country: United States
facility: Upmc Children'S Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Weill Medical College of Cornell University
name: Bernhard Kuhn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: El Khoudary SR, Fabio A, Yester JW, Steinhauser ML, Christopher AB, Gyngard F, Adams PS, Morell VO, Viegas M, Da Silva JP, Da Silva LF, Castro-Medina M, McCormick A, Reyes-Mugica M, Barlas M, Liu H, Thomas D, Ammanamanchi N, Sada R, Cuda M, Hartigan E, Groscost DK, Kuhn B. Design and rationale of a clinical trial to increase cardiomyocyte division in infants with tetralogy of Fallot. Int J Cardiol. 2021 Sep 15;339:36-42. doi: 10.1016/j.ijcard.2021.07.020. Epub 2021 Jul 12.