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Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Repair of Hypoplastic Left Heart Syndrome

Primary Purpose

Hypoplastic Left Heart Syndrome

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Autologous (self) mononuclear cells derived from umbilical cord blood

Stage II Surgical repair

About this trial

This is an interventional treatment trial for Hypoplastic Left Heart Syndrome focused on measuring Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord blood, Stem cells, Regenerative therapy, Stage II Glenn, Glenn Surgery, single ventricle

Eligibility Criteria

undefined - 12 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of HLHS or HLHS variant with single right ventricular dependent CHD having undergone Stage I surgical repair and undergoing Stage II surgical repair.
Less than 13 months of age at time of Stage II surgical repair
Previous participation in the UCB collection protocol with autologous UCB-MNC product that is acceptable for use (treatment arm only)

Exclusion Criteria:

History of DMSO reaction (treatment arm only).
Parent(s) and/or legal guardian(s) unwilling to have their child participate or unwilling to follow the study procedures.
Severe chronic diseases at the discretion of the treating physician.
Extensive extra-cardiac syndromic features.
Known history of cancer.
Any of the following complications of his/her congenital heart disease:
1. Any condition requiring urgent, or unplanned interventional procedure within 15 days prior to Stage II surgical repair, unless complete and full cardiac recovery is documented by site investigator
2. Severe pulmonary hypertension (reported in the medical record as >70% systemic pressure)
3. Other clinical concerns as documented by a site investigator that would predict (more likely to happen than not to happen) a risk of severe complications or very poor outcome, not directly related to the stem cell product or its injection procedure, during or after Stage II surgical repair.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Treatment

Control

Arm Description

Autologous (self) mononuclear cells derived from umbilical cord blood and that meet all release criteria are injected into the surface of the right heart muscle to achieve the target dose of 1-3 million cells per kilogram body weight . This is a one time treatment at the time of Stage II Glenn surgery .

Clinical data will be collected before, during and after the Stage II surgical standard of care procedure. Requires additional imaging studies at 3 months that are not standard of care in addition to some blood tests that would be beyond standard of care. Information will be collected to document the clinical outcomes and will be compared with the information from the group receiving the investigational treatment used in this study.

Outcomes

Primary Outcome Measures

Change in Right Ventricular Cardiac Function measured by apical fractional area change (FAC)

Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent.

Change in Right Ventricular Cardiac Function measured by circumferential strain.

Right ventricular cardiac function as measured by echocardiogram that includes studies for circumferential strain. Measured by percent.

Change in Right Ventricular Cardiac Function measured by longitudinal strain.

Right ventricular cardiac function as measured by echocardiogram that includes studies for longitudinal strain. Measured by percent.

Change in Right Ventricular Ejection Fraction

Right ventricular ejection fraction as measured by echocardiogram. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.

Secondary Outcome Measures

Change in ejection fraction

Ejection fraction as measured by echocardiogram. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.

Cumulative days of hospitalization

Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.

Change in weight

Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used.

Change in heart rate

Heart rate as measured at home by subject's caregiver as standard of care per subject's provider. Caregivers will be instructed by the site staff on the best way to perform.

Change in oxygen saturation

Oxygen saturation as measured at home by subject's caregiver using the pulse oximetry device provided as standard of care by subject's provider. Caregivers will be instructed by the site to use the same pulse oximetry device for every home measurement of oxygen saturation.

Change in weight

Change in heart failure medication

Changes in heart failure medications will be recorded by caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.

Change in arrhythmia medication

Changes in arrhythmia medication will be recorded by subject's caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.

Stage III surgical repair

The number of research subjects eligible for Stage III surgical repair

Total time until listed for cardiac transplantation

The number of days between Stage II surgery and listed on cardiac transplantation list.

Change in right ventricular function

Right ventricular ejection fraction as measured by echocardiogram, and cardiac catheterization. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.

Total time until death

The number of days between Stage II surgery and death occurrence

Full Information

NCT ID

NCT03779711

First Posted

December 4, 2018

Last Updated

May 5, 2023

Sponsor

Timothy J Nelson, MD, PhD

Collaborators

University of Oklahoma, Children's Hospital of Philadelphia, Children's Hospital Los Angeles, Children's Hospital Colorado, Children's Hospitals and Clinics of Minnesota, Ochsner Health System, Children's of Alabama, Children's Hospital Medical Center, Cincinnati

1. Study Identification

Unique Protocol Identification Number

NCT03779711

Brief Title

Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Repair of Hypoplastic Left Heart Syndrome

Official Title

Phase IIb Study of Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Stage II Surgical Repair of Right Ventricular Dependent Variants of Hypoplastic Left Heart Syndrome (AutoCell-S2)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 6, 2019 (Actual)

Primary Completion Date

May 22, 2022 (Actual)

Study Completion Date

February 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Timothy J Nelson, MD, PhD

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Researchers want to better understand what happens to the heart when the stem cells are injected directly into the muscle of the right side of the heart during the Stage II palliative surgery for single ventricle patients with hypoplastic left heart syndrome (HLHS) or HLHS variant. Researchers want to see if there are changes in the heart's structure/function following this stem cell-based therapy and compared to children that have not had cell-based therapy.

Detailed Description

This is a Phase IIb trial to determine if the delivery of the autologous UCB-MNC product into the myocardium of the right ventricle of the heart at the time of Stage II surgical repair will provide an improvement in cardiac function, reaching growth and developmental milestones, and quality of life, while also providing a reduction in the cumulative days of hospitalization following Stage II surgical repair. Long-term improvement in cardiac function, reaching growth and developmental milestones, reaching Stage III surgical repair pre-op work-up, prolonging time to cardiac transplantation or death, and improving quality of life will also be determined.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypoplastic Left Heart Syndrome

Keywords

Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord blood, Stem cells, Regenerative therapy, Stage II Glenn, Glenn Surgery, single ventricle

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

95 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Arm Title

Control

Arm Type

Active Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Autologous (self) mononuclear cells derived from umbilical cord blood

Intervention Description

The investigational product will be delivered into the right myocardium via sub-epicardial injections of 0.1 mL per kg body weight to achieve the target dose of 1-3 million TNC per kg body weight.at the time of Stage II surgical repair.

Intervention Type

Procedure

Intervention Name(s)

Stage II Surgical repair

Intervention Description

This operation usually is performed about six months after Stage I surgery to divert half of the blood to the lungs when circulation through the lungs no longer needs as much pressure from the ventricle. The shunt to the pulmonary arteries is disconnected and the right pulmonary artery is connected directly to the superior vena cava, the vein that brings deoxygenated blood from the upper part of the body to the heart. This sends half of the deoxygenated blood directly to the lungs without going through the ventricle.

Primary Outcome Measure Information:

Title

Change in Right Ventricular Cardiac Function measured by apical fractional area change (FAC)

Description

Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent.

Time Frame

baseline, 3 months post-Stage II surgery

Title

Change in Right Ventricular Cardiac Function measured by circumferential strain.

Description

Right ventricular cardiac function as measured by echocardiogram that includes studies for circumferential strain. Measured by percent.

Time Frame

baseline, 3 months post-Stage II surgery

Title

Change in Right Ventricular Cardiac Function measured by longitudinal strain.

Description

Right ventricular cardiac function as measured by echocardiogram that includes studies for longitudinal strain. Measured by percent.

Time Frame

baseline, 3 months post-Stage II surgery

Title

Change in Right Ventricular Ejection Fraction

Description

Time Frame

baseline, 12 months post-Stage II surgery

Secondary Outcome Measure Information:

Title

Change in ejection fraction

Description

Time Frame

baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks)

Title

Cumulative days of hospitalization

Description

Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.

Time Frame

1, 3-months post Stage II surgery

Title

Change in weight

Description

Time Frame

3-months post Stage II surgery

Title

Change in heart rate

Description

Heart rate as measured at home by subject's caregiver as standard of care per subject's provider. Caregivers will be instructed by the site staff on the best way to perform.

Time Frame

3-months post Stage II surgery

Title

Change in oxygen saturation

Description

Time Frame

3-months post Stage II surgery

Title

Change in weight

Description

Time Frame

baseline, every 6 months post-Stage II surgery

Title

Change in heart failure medication

Description

Changes in heart failure medications will be recorded by caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.

Time Frame

baseline, every 6 months post-Stage II surgery

Title

Change in arrhythmia medication

Description

Changes in arrhythmia medication will be recorded by subject's caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.

Time Frame

baseline, every 6 months post-Stage II surgery

Title

Stage III surgical repair

Description

The number of research subjects eligible for Stage III surgical repair

Time Frame

Stage III surgery pre-op, approx. 4 years

Title

Total time until listed for cardiac transplantation

Description

The number of days between Stage II surgery and listed on cardiac transplantation list.

Time Frame

up to Stage III surgery pre-op, approx. 4 years

Title

Change in right ventricular function

Description

Time Frame

baseline, Stage III surgery pre-op

Title

Total time until death

Description

The number of days between Stage II surgery and death occurrence

Time Frame

approx 4 years

10. Eligibility

Sex

All

Maximum Age & Unit of Time

12 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of HLHS or HLHS variant with single right ventricular dependent CHD having undergone Stage I surgical repair and undergoing Stage II surgical repair. Less than 13 months of age at time of Stage II surgical repair Previous participation in the UCB collection protocol with autologous UCB-MNC product that is acceptable for use (treatment arm only) Exclusion Criteria: History of DMSO reaction (treatment arm only). Parent(s) and/or legal guardian(s) unwilling to have their child participate or unwilling to follow the study procedures. Severe chronic diseases at the discretion of the treating physician. Extensive extra-cardiac syndromic features. Known history of cancer. Any of the following complications of his/her congenital heart disease: Any condition requiring urgent, or unplanned interventional procedure within 15 days prior to Stage II surgical repair, unless complete and full cardiac recovery is documented by site investigator Severe pulmonary hypertension (reported in the medical record as >70% systemic pressure) Other clinical concerns as documented by a site investigator that would predict (more likely to happen than not to happen) a risk of severe complications or very poor outcome, not directly related to the stem cell product or its injection procedure, during or after Stage II surgical repair.

Overall Study Officials: