Clinical trial NCT02549625: Phase I Safety and Feasibility Study of Intracoronary Delivery of Autologous Bone Marrow Derived Mononuclear Cells
Official title: Phase I Safety and Feasibility Study of Intracoronary Delivery of Autologous Bone Marrow Derived Mononuclear Cells for Systemic, Single Right Ventricular Failure Due to Congenital Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Congenital Heart Disease
Keywords: Single right ventricular failure
Lead sponsor: ReGen Theranostics, Inc.
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
First posted: 2015-09-15
Enrollment: 10
Sex: ALL
Minimum age (years): 2
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to determine the safety and feasibility of autologous mononuclear cells (MNC) collected from bone marrow (BM) and intracoronary delivery for individuals with declining performance of their single right ventricle systemic pumps. This procedure has the potential to foster a new strategy for congenital heart patients. This is an open-label study of autologous MNC derived from bone marrow with a 2-year follow-up to document 1) related serious adverse events and 2) monitor changes in cardiac structure and function.

Detailed description: This study is an open label Phase I trial to determine the safety and feasibility of bone marrow-derived mononuclear cells delivered into the coronary circulation of subjects with Fontan circulation and right ventricular dysfunction. Subjects will be screened at outpatient clinic visits at Mayo Clinic and interested qualified subjects will be consented and offered participation in this trial. Once informed consent has been obtained; preoperative values will be established and a selection committee will review subjects within three days prior to planned procedure to confirm inclusion and exclusion criteria. This will require a non-study cardiologist to review the clinical case and confirm the baseline cardiac function with evidence of disease progression with right ventricle dysfunction. However, individuals with decreased cardiac function requiring inotropic support and immediate listing for cardiac transplantation will NOT be included such that the risk of this research procedure may not be acceptable. Following cell-based product delivery, subjects will be followed for 6-months according to a pre-determined schedule that includes imaging studies along with questionnaires, electrophysiology and laboratory studies. Subjects will be contacted for an additional 18-months for surveillance by phone.

Eligibility criteria: Inclusion Criteria:

* Individuals with Fontan circulation with right ventricular dysfunction
* Ejection fraction equal to or less than 40% despite optimal outpatient medical management for at least 3 months
* Able to undergo bone marrow aspirate according to clinical consultation with hematology (INR must be maintained at or below 1.5)
* Able to undergo an MRI or CT examination

Exclusion Criteria:

* Individuals or parents of minors unwilling to consent to participation
* Individuals with severe chronic diseases, extra-cardiac syndromes, or cancer
* Females 10 years and older with positive pregnancy test or lack of effective birth control method
* Individuals currently requiring IV inotropes
* Individuals with bleeding disorders or history of thrombosis
* Individuals not eligible for MRI and have elevated serum creatinine level (eGFR less that 45 mL/min) and therefore cannot have a CT examination
* Individuals not eligible for MRI and have a prior significant reaction to intravenous contrast required for CT examination
* Individuals with the following conditions within 60 days prior to procedure:

  * Cardiogenic shock or extracorporeal circulation;
  * New arrhythmia that required medication for control;
  * Documented infection requiring treatment with antibiotics, and/or current infection being treated with antibiotics;
  * Cardiac condition requiring emergency procedure;
  * Cardiovascular surgery;
  * Seizures or history of significant neurological injury;
  * Multi-system organ failure including acute or chronic renal failure

Primary outcomes:
measure: Number of related serious adverse events
timeFrame: 6 months post cell delivery
Secondary outcomes:
measure: Number of subjects who died
timeFrame: 6 months post cell delivery
measure: Number of subjects with sustained or symptomatic ventricular arrhythmias
timeFrame: 6 months post cell delivery
measure: Number of subjects with acute decompensated heart failure
timeFrame: 6 months post cell delivery
measure: Number of subjects with myocardial infarction
timeFrame: 6 months post cell delivery
measure: Number of subjects with cardiac infection
timeFrame: 6 months post cell delivery
measure: Number of subjects with unexpected cardiovascular procedures within 6 months following cellular transplantation
timeFrame: 6 months post cell delivery
measure: Percentage of subjects that have cells delivered
timeFrame: 6 months post cell delivery
measure: Percentage of subjects completing the 6-month follow-up
timeFrame: 6 months post cell delivery
measure: Change in CT/MRI derived right ventricle ejection fraction
timeFrame: Baseline, 6 months post cell delivery
measure: Change in diastolic ventricular volume
timeFrame: Baseline, 6 months post cell delivery
measure: Change in systolic ventricular volume
timeFrame: Baseline, 6 months post cell delivery
measure: Change in echocardiography derived right ventricle ejection fraction
timeFrame: Baseline, 6 months post cell delivery
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Timothy J Nelson, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: Mayo Clinic
name: Muhammad Y Qureshi, MBBS
role: PRINCIPAL_INVESTIGATOR
References: