Clinical trial NCT03779711: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: ReGen Theranostics, Inc.
Sponsor class: OTHER
Collaborators: name: University of Oklahoma
name: Children's Hospital of Philadelphia
name: Children's Hospital Los Angeles
name: Children's Hospital Colorado
name: Children's Hospitals and Clinics of Minnesota
name: Ochsner Health System
name: Children's of Alabama
name: Children's Hospital Medical Center, Cincinnati
First posted: 2018-12-19
Enrollment: 95
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

  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.

Primary outcomes:
measure: Change in Right Ventricular Cardiac Function measured by apical fractional area change (FAC)
timeFrame: baseline, 3 months post-Stage II surgery
measure: Change in Right Ventricular Cardiac Function measured by circumferential strain.
timeFrame: baseline, 3 months post-Stage II surgery
measure: Change in Right Ventricular Cardiac Function measured by longitudinal strain.
timeFrame: baseline, 3 months post-Stage II surgery
measure: Change in Right Ventricular Ejection Fraction
timeFrame: baseline, 12 months post-Stage II surgery
Secondary outcomes:
measure: Change in ejection fraction
timeFrame: baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks)
measure: Cumulative days of hospitalization
timeFrame: 1, 3-months post Stage II surgery
measure: Change in weight
timeFrame: 3-months post Stage II surgery
measure: Change in heart rate
timeFrame: 3-months post Stage II surgery
measure: Change in oxygen saturation
timeFrame: 3-months post Stage II surgery
measure: Change in weight
timeFrame: baseline, every 6 months post-Stage II surgery
measure: Change in heart failure medication
timeFrame: baseline, every 6 months post-Stage II surgery
measure: Change in arrhythmia medication
timeFrame: baseline, every 6 months post-Stage II surgery
measure: Stage III surgical repair
timeFrame: Stage III surgery pre-op, approx. 4 years
measure: Total time until listed for cardiac transplantation
timeFrame: up to Stage III surgery pre-op, approx. 4 years
measure: Change in right ventricular function
timeFrame: baseline, Stage III surgery pre-op
measure: Total time until death
timeFrame: approx 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Orleans
country: United States
facility: Ocshner Medical Center
state: Louisiana
city: Minneapolis
country: United States
facility: Children's Hospitals of Minnesota
state: Minnesota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital and Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Mayo Clinic
name: Frank Cetta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Oklahoma University Medical Center
name: Harold M. Burkhart, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Joseph W. Rossano, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Minnesota
name: David M. Overman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Los Angeles
name: Ram Kumar Subramanyan, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Colorado
name: James Jaggers, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ochsner Health System
name: Benjamin Peeler, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemar Carlo, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: James Tweddell, M.D.
role: PRINCIPAL_INVESTIGATOR
References: