Clinical trial NCT02914171: Study of Autologous Bone Marrow Derived Mononuclear Cells for Treatment of Ebstein Anomaly
Official title: Phase I Safety and Feasibility Study of Intramyocardial Delivery of Autologous Bone Marrow Derived Mononuclear Cells to Right Ventricle of Patients With Ebstein Anomaly During Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ebstein Anomaly
Keywords: Myopathic right ventricle
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2016-09-26
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to determine the safety and feasibility of autologous mononuclear cells (MNS) collected from bone marrow (BM) and using an add-on intramyocardial delivery for individuals with Ebstein anomaly undergoing surgical intervention compared to the control group undergoing the same surgical procedure without cell delivery. This add-on procedure has the potential to foster a new strategy for individuals with congenital heart disease.This is an open-label study of autologous MNC derived from bone marrow with a 2-year follow-up to document 1) incidence and severity of adverse event 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 to the right ventricle of subjects with Ebstein anomaly at the time of a planned surgical Ebstein repair compared to the control group undergoing the same planned surgical intervention without the cell delivery add-on procedure. Subjects will be screened at outpatient clinic visits at Mayo Clinic and interested qualified subjects will be consented and offered participation in this trial. Subject/Family will decide to participate in cell delivery or control arm. Once informed consent has been obtained, subjects will undergo identical evaluation (other than Hematology consultation and BM harvest occurring only in the cell-treatment group),preoperative values will be established/confirmed and a selection committee will review subjects within three days prior to planned procedure to confirm inclusion and exclusion criteria.However, individuals at high-risk, primarily neonates and those with preoperative advanced right heart failure will NOT be included such that the risk of this add-on procedure may not be acceptable. Following surgical Ebstein repair for the control group and following cell-based product delivery for the treatment group, all subjects will be followed for 24-months according to a pre-determined schedule that includes imaging studies along with a questionnaire, electrophysiology and laboratory studies at 1, 6, and 24 months post procedure. All subjects will be contacted for surveillance by phone at 3, 12, and 18 month post procedure.

Eligibility criteria: Inclusion Criteria:

* Age 6 months to 30 years
* Individuals clinically planned for elective surgical Ebstein repair
* Individuals able to undergo bone marrow aspirate according to clinical consultation with Hematology (cell treatment group only)
* Individuals able to undergo preoperative MRI or CT examination
* Individual and/or parent willing and able to give informed consent and willing to commit to completion of follow-up

Exclusion Criteria:

* Individuals requiring cavopulmonary shunt at the time of surgical Ebstein repair; planned preoperatively or required intraoperatively
* Individuals with, or reasonably expected to have, complications during surgical Ebstein repair or during post-operative recovery
* Individual who have not completed or will not be completing all pre-procedure work-up within 30 days of surgical Ebstein repair AND lack of pre-procedure work-up documented as a safety concern by a site investigator
* Individuals who have other clinical concerns as documented by a site investigator that could reasonably increase the risk of complications during or after surgical Ebstein repair
* Individuals whose cells have been determined, by the sponsor, to not be acceptable for release to the investigational site or individual whose cells have been compromised after cells released to investigational site (cell treatment group only)
* Individuals who require surgery on pulmonary, mitral, or aortic valve
* Individuals with pulmonary atresia or atrioventricular discordance with ventriculoarterial discordance
* Individuals with history of ventricular arrhythmia or new onset ventricular arrhythmia after enrollment that requires medical management
* Individuals who have undergone previous sternotomy
* Individuals with preoperative ventricular arrhythmia requiring medical management
* Individuals with severe chronic diseases, extensive extra-cardiac syndromes, or history of any cancer
* Individuals with current IV inotrope requirements
* Individuals with bleeding disorders or history of thrombosis
* Subjects not eligible for MRI or CT examination due to either a medical contraindication, including acute or chronic renal failure
* Individuals with a currently active infection being treated with oral antibiotics
* Individuals with the following conditions within 60 days prior to Ebstein repair surgery:

  * Cardiogenic shock or extracorporeal circulation
  * Documented infection requiring treatment with intravenous antibiotics
  * Cardiac condition requiring emergency procedure
  * Current or uncontrolled seizures or neurological injury that has resulted in a persistent deficit
  * Multi-system organ failure including acute or chronic renal failure
* Female subjects 10 years and older with positive pregnancy test or lack of effective birth control method during the 30 days prior to surgical Ebstein repair
* Individuals who weigh more than 90 kg

Primary outcomes:
measure: Number of adverse events from time of index procedure
timeFrame: 24 months post index procedure
measure: Severity of adverse events from time of index procedure
timeFrame: 24 months post index procedure
measure: Number of subjects who died
timeFrame: 24 months post index procedure
measure: Number of subjects with sustained symptomatic cardiac arrhythmias
timeFrame: 24 months post index procedure
measure: Number of subjects with myocardial infarction
timeFrame: 24 months post index procedure
measure: Number of subjects with unexpected, invasive cardiovascular procedures
timeFrame: 24 months post index procedure
measure: Number of serious adverse events
timeFrame: 24 months post index procedure
measure: Percentage of subjects in the treatment group that have cells delivered
timeFrame: 24 months post index procedure
measure: Percentage of subjects in the treatment group completing the 24 month follow-up
timeFrame: 24 months post index procedure
measure: Incidence of cardiac related hospitalizations from time of Ebstein repair
timeFrame: 1, 6, and 24 months post index procedure
measure: Incidence of cardiac arrhythmias from time of index procedure
timeFrame: 1, 6, and 24 months post index procedure
measure: Change in CT derived right ventricular dimensions from time of pre-operative evaluation
timeFrame: 6 and 24 months post index procedure
measure: Change in echocardiography derived cardiac output from time of pre-operative evaluation
timeFrame: 1, 6, and 24 months post index procedure
measure: Change in NT-Pro-BNP derived cardiac function trend from time of pre-operative evaluation
timeFrame: During hospitalization up to 29 days, 1, 6 and 24 months post index procedure
measure: Incidence of cardiac related hospitalizations in the treatment group from time of pre-operative evaluation compared to the control group
timeFrame: 1, 6, and 24 months post index procedure
measure: Incidence of cardiac arrhythmias in the treatment group from time of pre-operative evaluation compared to the control group
timeFrame: 1, 6, and 24 months post index procedure
measure: Change in MRI derived cardiac output in the treatment group from time of pre-operative evaluation compared to the control group
timeFrame: 6 and 24 months post index procedure
measure: Change in echocardiography derived right ventricular dimensions from time of pre-operative evaluation
timeFrame: 1, 6, and 24 months post index procedure
measure: Change in NT-Pro-BNP derived cardiac function trend in the treatment group from time of pre-operative evaluation compared to the control group
timeFrame: During hospitalization up to 29 days, 1, 6, and 24 month post index procedure
measure: Number of serious adverse events from time of enrollment
timeFrame: index procedure
measure: Percentage of subjects in the treatment group whose cells meet all release criteria
timeFrame: 24 months post index procedure
measure: Change in CT derived cardiac output from time of pre-operative evaluation
timeFrame: 6 and 24 months post index procedure
measure: Change in MRI derived right ventricle ejection fraction in the treatment group from time of pre-operative evaluation compared to the control group
timeFrame: 6 and 24 months post index procedure
measure: Change in MRI derived right ventricular dimensions in the treatment group from time of pre-operative evaluation compared to the control group
timeFrame: 6 and 24 months post index procedure
measure: Change in CT derived right ventricle ejection fraction from time of pre-operative evaluation
timeFrame: 6 and 24 months post index procedure
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Muhammad Y Qureshi, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Timothy J Nelson, MD, PhD
role: STUDY_DIRECTOR
References:
citation: O'Leary PW, Qureshi MY, Cetta F, Nelson TJ, Holst KA, Dearani JA; Wanek Program Clinical Pipeline Group. Cone Reconstruction for Ebstein Anomaly: Ventricular Remodeling and Preliminary Impact of Stem Cell Therapy. Mayo Clin Proc. 2021 Dec;96(12):3053-3061. doi: 10.1016/j.mayocp.2021.02.015. Epub 2021 Sep 1.