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Study of Autologous Bone Marrow Derived Mononuclear Cells for Treatment of Ebstein Anomaly (Ebstein)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Timothy J. Nelson, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02914171
First received: September 22, 2016
Last updated: October 5, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention Phase
Ebstein Anomaly
Biological: Autologous Bone Marrow-derived Mononuclear Cells
Device: Insertable cardiac monitor
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Number of adverse events in the cell treatment arm [ Time Frame: 30 days post cell delivery ]
  • Severity of adverse events in the cell treatment arm [ Time Frame: 30 days post cell delivery ]
  • Number of subjects who died [ Time Frame: 24 months post Ebstein repair ]
  • Number of subjects with sustained or symptomatic ventricular arrhythmias [ Time Frame: 24 months post Ebstein repair ]
  • Number of subjects with myocardial infarction [ Time Frame: 24 months post Ebstein repair ]
  • Number of subjects with unexpected cardiovascular procedures [ Time Frame: 24 months post Ebstein repair ]
  • Number of serious adverse events [ Time Frame: 24 months post Ebstein repair ]
  • Percentage of subjects in the treatment group that have cells delivered [ Time Frame: 24 months post Ebstein repair ]
  • Percentage of subjects in the treatment group completing the 24 month follow-up [ Time Frame: 24 months post Ebstein repair ]
  • Incidence of cardiac related hospitalizations from time of pre-operative evaluation [ Time Frame: 1, 6, and 24 months post Ebstein repair ]
  • Incidence of atrial arrhythmias from time of pre-operative evaluation [ Time Frame: 1, 6, and 24 months post Ebstein repair ]
  • Change in CT/MRI derived right ventricle ejection fraction from time of pre-operative evaluation [ Time Frame: 6 and 24 months post Ebstein repair ]
  • Change in echocardiography derived cardiac output and right ventricular dimensions from time of pre-operative evaluation [ Time Frame: 1, 6, and 24 months post Ebstein repair ]
  • Change in NT-Pro-BNP derived cardiac function trend from time of pre-operative evaluation [ Time Frame: 6 and 24 months post Ebstein repair ]
  • Incidence of cardiac related hospitalizations in the treatment group from time of pre-operative evaluation compared to the control group [ Time Frame: 1, 6, and 24 months post Ebstein repair ]
  • Incidence of atrial arrhythmias in the treatment group from time of pre-operative evaluation compared to the control group [ Time Frame: 1, 6, and 24 months post Ebstein repair ]
  • Change in CT/MRI derived right ventricle ejection fraction in the treatment group from time of pre-operative evaluation compared to the control group [ Time Frame: 6 and 24 months post Ebstein repair ]
  • Change in echocardiography derived cardiac output and right ventricular dimensions in the treatment group from time of pre-operative evaluation compared to the control group [ Time Frame: 1, 6, and 24 months post Ebstein repair ]
  • Change in NT-Pro-BNP derived cardiac function trend in the treatment group from time of pre-operative evaluation compared to the control group [ Time Frame: 1, 6, and 24 month post Ebstein repair ]

Estimated Enrollment: 20
Study Start Date: September 2016
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment arm
Individuals with Ebstein anomaly and underlying myopathic right ventricle undergoing planned surgical intervention using an add-on procedure delivering autologous bone marrow-derived mononuclear cells into the right ventricle.
Biological: Autologous Bone Marrow-derived Mononuclear Cells
Other Name: MNC
Device: Insertable cardiac monitor
Following surgical Ebstein repair a Medtronic Reveal LINQ Insertable Cardiac Monitor (ICM) will be placed subcutaneously in the anterior chest to continuously monitor the subject's heart rhythm and to record cardiac information through automatic detection of arrhythmias.
Other Names:
  • ICM
  • ILR
Control arm
Individuals with Ebstein anomaly and underlying myopathic right ventricle undergoing planned surgical intervention without cell delivery.
Device: Insertable cardiac monitor
Following surgical Ebstein repair a Medtronic Reveal LINQ Insertable Cardiac Monitor (ICM) will be placed subcutaneously in the anterior chest to continuously monitor the subject's heart rhythm and to record cardiac information through automatic detection of arrhythmias.
Other Names:
  • ICM
  • ILR

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. This will require a non-study cardiologist to review the clinical case and confirm the baseline cardiac function with evidence of right ventricle dysfunction. 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

Ages Eligible for Study:   6 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 intervention; planned preoperatively or required intraoperatively (pre-operative cardiothoracic ratio >0.65, right ventricular end-diastolic volume >250mL/m², or right ventricular ejection fraction ≤25% will be excluded due to increased likelihood of requiring cavopulmonary shunt)
  • Individuals who require tricuspid valve replacement
  • 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
  • Individuals who have undergone previous cardiac operations
  • Individuals with preoperative ventricular arrhythmia requiring medical management
  • Individuals with severe chronic diseases, 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 1) elevated serum creatinine level (eGFR <45mL/min), 2) prior significant reaction to intravenous contrast required for MRI or CT examination
  • Individuals with the following conditions within 60 days prior to surgery:

    • Cardiogenic shock or extracorporeal circulation
    • Documented infection requiring treatment with intravenous and/or oral antibiotics
    • Cardiac condition requiring emergency procedure
    • Seizures or history of significant neurological injury
    • 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 procedure
  • Individuals who weigh more than 90 kg secondary to cell-product dosing restrictions

The cell-product will not be delivered in subjects in the cell-treatment group after confirmation of cell-product not meeting release criteria by the Human Cellular Therapy Laboratory Manufacturing team.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02914171

Contacts
Contact: Karen M Cavanaugh, CCRP 507-538-8425 cavanaugh.karen@mayo.edu
Contact: Riess A Lori, CCRP 507-538-7730 riess.lori@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Karen M Cavanaugh, CCRP    507-538-8425    cavanaugh.karen@mayo.edu   
Contact: Lori A Riess, CCRP    507-538-7730    riess.lori@mayo.edu   
Principal Investigator: Muhammad Y Qureshi, MBBS         
Sponsors and Collaborators
Timothy J. Nelson
Investigators
Principal Investigator: Muhammad Y Qureshi, MBBS Mayo Clinic
Study Director: Timothy J Nelson, MD, PhD Mayo Clinic
  More Information

Responsible Party: Timothy J. Nelson, Program Director, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02914171     History of Changes
Other Study ID Numbers: 15-007580
Study First Received: September 22, 2016
Last Updated: October 5, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Mayo Clinic:
Myopathic right ventricle

Additional relevant MeSH terms:
Congenital Abnormalities
Ebstein Anomaly
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on March 23, 2017