Beta-blocker Administration for Cardiomyocyte Division

NCT ID: NCT04713657

Last Updated: 2025-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-16

Study Completion Date

2030-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Tetralogy of Fallot Double Outlet Right Ventricle

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

double-blinded, placebo-controlled (1:1) randomized, single-center trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Propranolol

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.

Group Type ACTIVE_COMPARATOR

N-thymidine

Intervention Type OTHER

15N-thymidine will be administered to patients in order to quantify cardiomyocyte proliferation. 15N-thymidine will be administered as 5 separate syringes. Each syringe will contain the recommended daily dose based on participants weight. Subjects will be given the labeled thymidine by mouth once a day for 5 consecutive days. The dosing will begin one week after starting the study drug.The caregiver (parent or nurse) will administer the labeled thymidine by mouth via a syringe once a day for 5 consecutive days. They will be provided with a diary to keep track of study drug dosing.

Urine Collection

Intervention Type OTHER

Parents will be asked to keep a diary of the child's feeding and diaper changes during the administration of thymidine. To monitor how the labeled thymidine is processed in the body, investigators will analyze urine from the child's diapers. Each time a diaper is changed, a cotton ball will be placed in the diaper. At the next diaper change, this cotton ball will be removed from the diaper, placed in a Ziploc bag, and stored in the freezer. They will be collected and stored cotton balls starting with the first administration of thymidine until 24 hours after the last administration. The frozen cotton balls may be collected from the home by a nurse or brought by parent to the next clinic visit.

Echocardiogram

Intervention Type PROCEDURE

On Study Day 1 to obtain baseline assessment of cardiac size. A second research dedicated echocardiogram will be done after being anesthetized for surgery. Echocardiography is routinely performed to determine right ventricle (RV) structure of the heart and function in Tetrology of Fallot/ Pulmonary Stenosis (ToF/PS) and is non-invasive.

Cardiac MRI (CMR)

Intervention Type PROCEDURE

A limited study protocol will be performed using the feed-and-bundle technique at the time of study enrollment, The feed and bundle technique is utilized so that the infant will be as comfortable as possible and asleep during the procedure. This is done to prevent the risk of sedation and allow for a more natural sleep. The baby is undressed, prepared with ECG-leads and an oxygen saturation probe, and fed. With this "feed, swaddle, and sleep" technique, scanning times of 30-60 minutes can be achieved, which provides the stillness needed for accurate visualization of the heart. A second CMR, with the same limited study protocol, will be performed under general anesthesia prior to surgical repair. It does not pose any risk of radiation exposure and will not require IV placement or contrast administration for a limited assessement of the right ventricle.

Propranolol Hydrochloride

Intervention Type DRUG

For patients who are randomized to receive propranolol, The target dose for this study will be 4 mg/kg/day divided in 4 doses. The first dose will be given in the Pediatric Clinical and Translational Research Center (PCTRC) at 1mg/kg. Parents will administer propranolol (1 mg/kg po x 4 doses per day). Parents will be instructed to administer propranolol with feeding or soon after feeding, but not before feeding. families will also be given instructions for regarding 15N-thymidine dosing frequency and interval and provided with a log sheet to record administered and missed doses of propranolol and 15N-thymidine.

Physical Exam

Intervention Type PROCEDURE

On Study Day 1; monthly until surgery in conjunction with patient's clinical cardiology appointment; and at the time of surgery. Will include vital signs.

Specimen Collection

Intervention Type OTHER

On the morning of surgery, after IV access is obtained for anesthesia 2 ml of blood will be collected for analysis. A small piece of heart tissue and fat that has already been removed during surgery will be collected for analysis.

Placebo

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.

Group Type PLACEBO_COMPARATOR

N-thymidine

Intervention Type OTHER

15N-thymidine will be administered to patients in order to quantify cardiomyocyte proliferation. 15N-thymidine will be administered as 5 separate syringes. Each syringe will contain the recommended daily dose based on participants weight. Subjects will be given the labeled thymidine by mouth once a day for 5 consecutive days. The dosing will begin one week after starting the study drug.The caregiver (parent or nurse) will administer the labeled thymidine by mouth via a syringe once a day for 5 consecutive days. They will be provided with a diary to keep track of study drug dosing.

Urine Collection

Intervention Type OTHER

Parents will be asked to keep a diary of the child's feeding and diaper changes during the administration of thymidine. To monitor how the labeled thymidine is processed in the body, investigators will analyze urine from the child's diapers. Each time a diaper is changed, a cotton ball will be placed in the diaper. At the next diaper change, this cotton ball will be removed from the diaper, placed in a Ziploc bag, and stored in the freezer. They will be collected and stored cotton balls starting with the first administration of thymidine until 24 hours after the last administration. The frozen cotton balls may be collected from the home by a nurse or brought by parent to the next clinic visit.

Echocardiogram

Intervention Type PROCEDURE

On Study Day 1 to obtain baseline assessment of cardiac size. A second research dedicated echocardiogram will be done after being anesthetized for surgery. Echocardiography is routinely performed to determine right ventricle (RV) structure of the heart and function in Tetrology of Fallot/ Pulmonary Stenosis (ToF/PS) and is non-invasive.

Cardiac MRI (CMR)

Intervention Type PROCEDURE

A limited study protocol will be performed using the feed-and-bundle technique at the time of study enrollment, The feed and bundle technique is utilized so that the infant will be as comfortable as possible and asleep during the procedure. This is done to prevent the risk of sedation and allow for a more natural sleep. The baby is undressed, prepared with ECG-leads and an oxygen saturation probe, and fed. With this "feed, swaddle, and sleep" technique, scanning times of 30-60 minutes can be achieved, which provides the stillness needed for accurate visualization of the heart. A second CMR, with the same limited study protocol, will be performed under general anesthesia prior to surgical repair. It does not pose any risk of radiation exposure and will not require IV placement or contrast administration for a limited assessement of the right ventricle.

Placebo

Intervention Type DRUG

For patients who are randomized to receive placebo, the first dose will be given in the Pediatric Translational Research Center (PCTRC) and will be based on the patients weight. Parents will administer placebo 4 doses per day. 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.

Physical Exam

Intervention Type PROCEDURE

On Study Day 1; monthly until surgery in conjunction with patient's clinical cardiology appointment; and at the time of surgery. Will include vital signs.

Specimen Collection

Intervention Type OTHER

On the morning of surgery, after IV access is obtained for anesthesia 2 ml of blood will be collected for analysis. A small piece of heart tissue and fat that has already been removed during surgery will be collected for analysis.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

N-thymidine

15N-thymidine will be administered to patients in order to quantify cardiomyocyte proliferation. 15N-thymidine will be administered as 5 separate syringes. Each syringe will contain the recommended daily dose based on participants weight. Subjects will be given the labeled thymidine by mouth once a day for 5 consecutive days. The dosing will begin one week after starting the study drug.The caregiver (parent or nurse) will administer the labeled thymidine by mouth via a syringe once a day for 5 consecutive days. They will be provided with a diary to keep track of study drug dosing.

Intervention Type OTHER

Urine Collection

Parents will be asked to keep a diary of the child's feeding and diaper changes during the administration of thymidine. To monitor how the labeled thymidine is processed in the body, investigators will analyze urine from the child's diapers. Each time a diaper is changed, a cotton ball will be placed in the diaper. At the next diaper change, this cotton ball will be removed from the diaper, placed in a Ziploc bag, and stored in the freezer. They will be collected and stored cotton balls starting with the first administration of thymidine until 24 hours after the last administration. The frozen cotton balls may be collected from the home by a nurse or brought by parent to the next clinic visit.

Intervention Type OTHER

Echocardiogram

On Study Day 1 to obtain baseline assessment of cardiac size. A second research dedicated echocardiogram will be done after being anesthetized for surgery. Echocardiography is routinely performed to determine right ventricle (RV) structure of the heart and function in Tetrology of Fallot/ Pulmonary Stenosis (ToF/PS) and is non-invasive.

Intervention Type PROCEDURE

Cardiac MRI (CMR)

A limited study protocol will be performed using the feed-and-bundle technique at the time of study enrollment, The feed and bundle technique is utilized so that the infant will be as comfortable as possible and asleep during the procedure. This is done to prevent the risk of sedation and allow for a more natural sleep. The baby is undressed, prepared with ECG-leads and an oxygen saturation probe, and fed. With this "feed, swaddle, and sleep" technique, scanning times of 30-60 minutes can be achieved, which provides the stillness needed for accurate visualization of the heart. A second CMR, with the same limited study protocol, will be performed under general anesthesia prior to surgical repair. It does not pose any risk of radiation exposure and will not require IV placement or contrast administration for a limited assessement of the right ventricle.

Intervention Type PROCEDURE

Propranolol Hydrochloride

For patients who are randomized to receive propranolol, The target dose for this study will be 4 mg/kg/day divided in 4 doses. The first dose will be given in the Pediatric Clinical and Translational Research Center (PCTRC) at 1mg/kg. Parents will administer propranolol (1 mg/kg po x 4 doses per day). Parents will be instructed to administer propranolol with feeding or soon after feeding, but not before feeding. families will also be given instructions for regarding 15N-thymidine dosing frequency and interval and provided with a log sheet to record administered and missed doses of propranolol and 15N-thymidine.

Intervention Type DRUG

Placebo

For patients who are randomized to receive placebo, the first dose will be given in the Pediatric Translational Research Center (PCTRC) and will be based on the patients weight. Parents will administer placebo 4 doses per day. 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.

Intervention Type DRUG

Physical Exam

On Study Day 1; monthly until surgery in conjunction with patient's clinical cardiology appointment; and at the time of surgery. Will include vital signs.

Intervention Type PROCEDURE

Specimen Collection

On the morning of surgery, after IV access is obtained for anesthesia 2 ml of blood will be collected for analysis. A small piece of heart tissue and fat that has already been removed during surgery will be collected for analysis.

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Thymidine Propranolol

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

30 Days

Maximum Eligible Age

60 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Bernhard Kuhn, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Weill Cornell Medicine

New York, New York, United States

Site Status RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Upmc Children'S Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Rashida Blackwood, BS, MPH

Role: CONTACT

646-962-9036

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Rashida Blackwood, BS, MPH

Role: primary

646-962-9036

Laura Mercer-Rosa, MD

Role: primary

Anh Duc Mai

Role: backup

Shannon Janzef, RN

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 34265312 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01HL155597

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-12026881

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

TRICuspid Intervention in Heart Failure Trial
NCT04634266 ACTIVE_NOT_RECRUITING NA
TRILUMINATE Pivotal Trial
NCT03904147 ACTIVE_NOT_RECRUITING NA
AltaValve Pivotal Trial
NCT06465745 RECRUITING NA