Hypoplastic Left Heart Syndrome
Conditions
Keywords
stem cells, pediatric
Brief summary
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 Bidirectional Cavopulmonary Anastomosis (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.
Interventions
BIOLOGICALc-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.
Sponsors
Joshua M Hare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The first 10 participants will be enrolled in Group A to assess safety and feasibility. An additional 22 participants will be enrolled in Group B and will be randomized to either the Treatment or Control Group.
Eligibility
Sex/Gender
ALL
Age
1 Days to 21 Days
Healthy volunteers
No
Inclusion criteria
* For inclusion in the study, subjects must meet all of the inclusion criteria: 1. Subjects with hypoplastic left heart syndrome (HLHS) (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 B surface antigen or viremic hepatitis C and Treponema pallidum. 5. Subjects who are unsuitable for inclusion in the study in the opinion of the investigator(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Incidence of Treatment Related Major Adverse Cardiac Events | 30 days | 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. |
| Number of C-kit+ Products | Day 1 | Feasibility will be reported as the number of c-kit+ products that can be manufactured and delivered to subjects |
| Number of Participants Completing Magnetic Resonance Imaging (MRI) | Baseline, 6 Months, 12 months | Feasibility will be reported as the number of participants that complete the baseline, 6-months, and 12-months follow up MRI. |
| Change in Right Ventricular Function (RVEF) | Baseline, 6 Months, 12 months | 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. |
| Change in Right Ventricular End-diastolic Volume (RVEDV) | Baseline, 6 months, 12 months | Efficacy will be reported as the change in right ventricular end-diastolic assessed in milliliters per square meter and will be measured using serial echocardiograms and MRI scan. |
| Change in Right Ventricular End-systolic Volume (RVESV) | Baseline, 6 months, 12 months | Efficacy will be reported as the change in right ventricular end-systolic volume assessed in milliliters per square meter and will be measured using serial echocardiograms and MRI scan. |
| Change in Tricuspid Regurgitation | Baseline, 6 months, 12 months | Efficacy will be reported as the change tricuspid regurgitation assessed as a percentage and will be measured using serial echocardiograms and MRI scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Incidence of Serious Adverse Events | Up to 12 months | 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. |
| Change in Somatic Growth Velocity - Length (cm) | Baseline, 6 months, 12 months | Changes in somatic growth velocity will be evaluated by length (cm) over 12 months post study product injection. |
| Change in Somatic Growth Velocity - Weight (kg) | Baseline, 6 months, 12 months | Changes in somatic growth velocity will be evaluated by weight (kg) over 12 months post study product injection. |
| Change in Somatic Growth Velocity - Head Circumference (cm) | Baseline, 6 months, 12 months | Changes in somatic growth velocity will be evaluated by head circumference (cm) over 12 months post study product injection. |
| Change in Infant Toddler Quality of Life Survey (ITQOL) - Overall Health | Baseline, 12 months | The Infant Toddler Quality of Life Survey (ITQOL) is a validated 47-item parent-reported questionnaire assessing multiple domains of child health, including overall health, physical abilities, growth and development, discomfort/pain, mood, and behavior. Domain scores are transformed to a 0-100 scale, where 0 reflects the poorest health-related quality of life and 100 reflects the best. Higher scores indicate better quality of life. |
| Incidence of Mortality or Need for Transplantation | Up to 12 months | Incidence of mortality or need for transplantation after the Stage II BDCPA operation will be reported |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORWilliam Mahle, MD
Emory University
PRINCIPAL_INVESTIGATORKristopher Deatrick, MD
University of Maryland
PRINCIPAL_INVESTIGATORRichard Ohye, MD
Michigan Medicine Congenital Heart Center/C.S. Mott Children's Hospital
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 4.51 Months STANDARD_DEVIATION 0.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 1 / 8 |
| other Total, other adverse events | 5 / 9 | 6 / 8 | 6 / 8 |
| serious Total, serious adverse events | 8 / 9 | 4 / 8 | 4 / 8 |
Outcome results
None listed