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

T

Timothy J. Nelson

Status and phase

Completed
Phase 1

Conditions

Ebstein Anomaly

Treatments

Biological: Autologous Bone Marrow-derived Mononuclear Cells
Device: Insertable cardiac monitor

Study type

Interventional

Funder types

Other

Identifiers

NCT02914171
15-007580

Details and patient eligibility

About

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.

Full 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.

Enrollment

10 patients

Sex

All

Ages

6 months to 30 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

10 participants in 2 patient groups

Treatment arm
Experimental group
Description:
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.
Treatment:
Device: Insertable cardiac monitor
Biological: Autologous Bone Marrow-derived Mononuclear Cells
Control arm
Other group
Description:
Individuals with Ebstein anomaly and underlying myopathic right ventricle undergoing planned surgical intervention without cell delivery.
Treatment:
Device: Insertable cardiac monitor

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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