Transplantation of Autologously Derived Mitochondria Following Ischemia

Not Applicable

Recruiting

• Conditions: Extracorporeal Membrane Oxygenation Complication
• Interventions: Other: autologous mitochondria transplantation

• Registration Number: NCT02851758
• Lead Sponsor: Boston Children's Hospital

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-07-25
• Study First Submitted QC: 2016-07-28
• Study First Posted: 2016-08-02
• Study Start: 2017-08-02
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-09
• Last Update Posted: 2023-01-11
• Primary Completion: 2024-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

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

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Exclusion Criteria

• Known mitochondria disorders

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Autologous mitochondria injection	autologous mitochondria transplantation	All subjects will have autologous mitochondria injected into ischemic areas of the myocardium (via injection or infusion).

Primary Outcome Measures

Name	Time	Method
Safety- Incidence of severe adverse events	1 week	Subjects will be SAE free for one week following injection

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States