Transplantation of Autologously Derived Mitochondria Following Ischemia

Transplantation of Autologously Derived Mitochondria for Protection Against Ischemia-reperfusion Injury Following Ischemia in Subjects on ECMO Support

The investigators propose a robust therapeutic intervention to ameliorate myocardial ischemia/ reperfusion injury and significantly decrease morbidity and mortality in patients requiring extracorporeal membrane oxygenation (ECMO), by direct injection of autogeneic mitochondria into the ischemic myocardium.

Study Overview

• Status: Recruiting
• Conditions: Extracorporeal Membrane Oxygenation Complication
• Intervention / Treatment: Other: autologous mitochondria transplantation

Detailed Description

Autologous mitochondria will be delivered to the ischemic heart muscle in one of two ways, during clinically indicated surgical procedure or during clinically indicated cardiac catheterization.

For surgical re-operation subjects:

After the subject's chest is open, 1-2 6mm biopsies will be collected from the exposed skeletal muscle of the chest wall. The tissue will be processed at bedside to extract the autologous mitochondria. Surgery will proceed as clinically indicated. Prior to closure of the chest, autologous mitochondria will be injected via 5-10 injections of approximately 0.1 mL each to the damaged area (if damaged muscle is local) or via injection into the proximal aorta while cross-clamped for clinically indicated surgery for global distribution of mitochondria via the coronary arteries if there is no evident area of damage. Following completion of surgical maneuvers the mitochondria will be injected into the aorta and the cross-clamp will be removed. If there is global injury but a cross-clamp is not clinically indicated, direct injection into the myocardium will occur throughout the ventricle as previously described. Chest closure will then occur as and if clinically indicated for both techniques.

For catheterization subjects:

Once in the catheterization lab, the temporary chest closure will be removed and 1-2 6 mm biopsies will be collected from the exposed skeletal muscle of the chest wall by the cardiac surgery team. The tissue will be processed at bedside to extract the autologous mitochondria. The catheterization will proceed as clinically indicated. Prior to completion of the procedure (interventional to restore blood flow or hemodynamics), mitochondria will be infused in 5 mL of buffer as conducted in large animal studies (5) via intracoronary infusion followed by a 5 mL flush with normal saline. Total dose of mitochondria will be equal to direct injection subjects, with a larger dilution to allow to infusion via cardiac catheter.

If there is no marked improvement in ventricular function following the injection/infusion of autologous mitochondria and the subject has a clinically indicated procedure in the days following the initial delivery, a second injection/infusion will be completed. At this time the follow up schedule will be reset to Day 0.

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Breanna Piekarski, RN, BSN; Phone Number: 617-919-4457; Email: breanna.piekarski@cardio.chboston.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Breanna Piekarski, RN, BSN; Phone Number: 617-919-4457; Email: breanna.piekarski@cardio.chboston.org
      • Principal Investigator: Sitaram M Emani, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric cardiology patients under the age of 18 on ECMO
• concerns for ischemic injury on the Cardiac Intensive Care Unit

Exclusion Criteria:

• Known mitochondria disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous mitochondria injection; All subjects will have autologous mitochondria injected into ischemic areas of the myocardium (via injection or infusion).	Other: autologous mitochondria transplantation; Autologous mitochondria obtained from the subject's own skeletal muscle will be injected or infused into the ischemic myocardium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety- Incidence of severe adverse events	Subjects will be SAE free for one week following injection	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy- Improvement in Outcome measures: increased ventricular function on echocardiogram, measured by ejection fraction	Improvement in ventricular function	1 week- 1 month
Efficacy- Improvement in Outcome measures: ability to be separated from ECMO support, measured in days since injection	The ability to decannulate from ECMO support	1 week- 1 month

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Investigators: Principal Investigator: Sitaram M Emani, MD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2017
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimate): August 2, 2016

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: IRB-P00014558

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No