The CHILD Trial: Hypoplastic Left Heart Syndrome Study. (CHILD)

Autologous Cardiac Stem Cell Injection in Patients With Hypoplastic Left Heart Syndrome: An Open Label Pilot Study.

The objectives of this pilot study are to evaluate the feasibility and safety of intramyocardial injection of autologous c-kit+ cells during the Stage II BDCPA operation and to observe effects on clinical outcome including right ventricular myocardial function, severity of tricuspid regurgitation, incidence of serious adverse events, re-hospitalizations, changes in health status, the need for transplantation, or mortality.

Study Overview

• Status: Recruiting
• Conditions: Hypoplastic Left Heart Syndrome
• Intervention / Treatment: Biological: c-kit+ cells

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yvenie Desire, BA; Phone Number: 305-243-7273; Email: YDesire@miami.edu
• Study Contact Backup: Name: Joshua M Hare, MD; Phone Number: 305-243-5779; Email: JHare@med.miami.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Children's Healthcare of Atlanta - Egleston Campus
      • Contact: Kristen Herzegh, MPH; Phone Number: 404-712-7596; Email: kcoshau@emory.edu
      • Sub-Investigator: Michael Davis, PhD
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland - Division of Cardiac Surgery
      • Contact: Manal Al-Suqi, MSTC; Phone Number: 410-328-9409; Email: MaAl-Suqi@som.umaryland.edu
      • Contact: Kristopher Deatrick, MD; Phone Number: 410-328-5842; Email: KDeatrick@som.umaryland.edu
      • Principal Investigator: Kristopher Deatrick
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • Michigan Medicine Congenital Heart Center/C.S. Mott Children's Hospital
      • Contact: Tammy Doman, RN; Phone Number: 734-763-6109; Email: tpaterso@med.umich.edu
      • Principal Investigator: Richard Ohye, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 weeks (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• For inclusion in the study, subjects must meet all of the inclusion criteria:

  1. Subjects with hypoplastic left heart syndrome (all types) requiring Stage I Norwood operation.

     Exclusion Criteria:

• Candidates will be excluded from the study if any of the following conditions are met:

  1. Subjects undergoing the Stage I Norwood operation who do not have HLHS.
  2. Subjects requiring mechanical circulatory support immediately prior to Stage II BDCPA operation (within 5 days).
  3. Parent or guardian unwilling or unable to comply with necessary follow-up(s).
  4. Mother is serum positive for HIV 1/2, hepatitis BsAg or viremic hepatitis C and Treponema pallidum.
  5. Subjects who are unsuitable for inclusion in the study in the opinion of the investigator(s).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label C-kit+ cells Group A; Group A is an open-label treatment group determining safety and feasibility. Participants enrolled in this group will be receiving previously harvested c-kit+ cells during their Stage II BDCPA operation. Harvested c-kit+ cells will be injected into the right ventricle directly intramyocardially.	Biological: c-kit+ cells; The autologous c-kit+ cells will be harvested from participant's right atrial tissue obtained from participant's SOC Norwood Operation. The harvested c-kit+ cells containing up to a total of 12,500 cells/kg will be delivered through 6-10 intramyocardial injections of approximately 100uL per injection for a total volume of approximately 0.6 mL.; Other Names: Autologous c-kit-positive cells (c-kit+ cells)
Active Comparator: C-kit+ cells Group B; Participants randomized to Group B Treatment Group will receive previously harvested c-kit+ cells during their Stage II BDCPA operation. Harvested c-kit+ cells will be injected into the right ventricle directly intramyocardially.	Biological: c-kit+ cells; The autologous c-kit+ cells will be harvested from participant's right atrial tissue obtained from participant's SOC Norwood Operation. The harvested c-kit+ cells containing up to a total of 12,500 cells/kg will be delivered through 6-10 intramyocardial injections of approximately 100uL per injection for a total volume of approximately 0.6 mL.; Other Names: Autologous c-kit-positive cells (c-kit+ cells)
No Intervention: No Intervention Group; Participants randomized to Group B Control Group will receive only their standard of care (SOC) Stage II BDCPA operation without the injection of harvested c-kit+ cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Incidence of Treatment Related Major Adverse Cardiac Events	Safety will be reported as the number of incidence of treatment related major adverse cardiac events (MACE). MACE is defined as any of the following: greater than 30 seconds of sustained/symptomatic ventricular tachycardia requiring intervention, cardiogenic shock, unplanned cardiovascular operation due to injection site bleeding, need for new permanent pacemaker, stroke or embolic event to the brain determined by CT scan and death. MACE will be evaluated by the treating physician and assessed using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.	30 days
Number of c-kit+ products	Feasibility will be reported as the number of c-kit+ products that can be manufactured and delivered to subjects	Day 1
Number of participants completing Magnetic Resonance Imaging (MRI)	Feasibility will be reported as the number of participants that complete the baseline, 6-months, and 12-months follow up MRI.	12 months
Change in right ventricular function	Efficacy will be reported as the change in right ventricular function assessed as a percentage and will be measuring using serial echocardiograms and MRI scan.	Baseline, 12 months
Change in Right Ventricular End-diastolic Volume	Efficacy will be reported as the change in right ventricular end-diastolic assessed in mL and will be measured using serial echocardiograms and MRI scan.	Baseline, 12 months
Change in Right Ventricular End-systolic Volume	Efficacy will be reported as the change in right ventricular end-systolic volume assessed in mm and will be measured using serial echocardiograms and MRI scan.	Baseline, 12 months
Change in Tricuspid Regurgitation	Efficacy will be reported as the change tricuspid regurgitation assessed in m/s and will be measured using serial echocardiograms and MRI scan.	Baseline, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Incidence of Serious Adverse Events	Incidence of the following after the BDCPA / GLENN Procedure including: All-cause mortality; Cardiovascular mortality; Need for transplantation; Hospitalization for heart failure; Cardiovascular morbidity, including stroke or heart failure or sustained/symptomatic arrhythmias.	Up to 12 months
Change in somatic growth velocity	Changes in somatic growth velocity will be evaluated by weight, height, head circumference over 12 months post-SPI.	Baseline, 12 months
Change in Infant Toddler Quality of Life Survey (ITQOL)	Change in Infant Toddler Quality of Life Survey (ITQOL) is measured on a 9 scale with 47 items measuring child's overall health, physical abilities, overall growth and development, discomfort/pain, moods, and overall behavior. The total score ranges from 0 to 100 with the higher score indicating better quality of life.	Baseline, 12 months
Incidence of mortality or need for transplantation	Incidence of mortality or need for transplantation after the Stage II BDCPA operation will be reported	Up to 12 months

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Kristopher Deatrick, MD, University of Maryland; Principal Investigator: Richard Ohye, MD, Michigan Medicine Congenital Heart Center/C.S. Mott Children's Hospital; Principal Investigator: William Mahle, MD, Emory University

Publications and helpful links

General Publications

• Kaushal S, Hare JM, Shah AM, Pietris NP, Bettencourt JL, Piller LB, Khan A, Snyder A, Boyd RM, Abdullah M, Mishra R, Sharma S, Slesnick TC, Si MS, Chai PJ, Davis BR, Lai D, Davis ME, Mahle WT. Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study). Pediatr Cardiol. 2022 Oct;43(7):1481-1493. doi: 10.1007/s00246-022-02872-6. Epub 2022 Apr 8.
• Ali MK, Ichimura K, Spiekerkoetter E. Promising therapeutic approaches in pulmonary arterial hypertension. Curr Opin Pharmacol. 2021 Aug;59:127-139. doi: 10.1016/j.coph.2021.05.003. Epub 2021 Jun 30.

Helpful Links

• Interdisciplinary stem cell institute at the University of Miami website

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2019
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: January 19, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: pediatric; stem cells
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Syndrome; Hypoplastic Left Heart Syndrome
• Other Study ID Numbers: 20190743

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No