Autologous Mitochondrial Transplant for Cerebral Ischemia

Study Overview
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Brief Summary
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The investigators propose to infuse healthy autologous mitochondria into cerebral vessels supplying brain tissue experiencing ischemia in patients who undergo standard-of- care endovascular reperfusion therapy.

Detailed Description
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Stroke is one of the leading causes of morbidity and mortality worldwide. More than 80% of strokes are the result of ischemia caused by blockage of one or more cerebral arteries. Lack of blood supply starves brain cells of necessary glucose and oxygen, and disturbs cellular homeostasis, eventually resulting in neuronal death. Mitochondria are tiny organelles present in nearly all types of human cells and are vital to our survival. Much like a battery, they generate most of our adenosine triphosphate (ATP), the energy currency of the cell. Mitochondria are also involved in other tasks, such as signaling between cells and cell death. All these functions can be impaired during ischemia because of the damage caused to mitochondria. Based on many preclinical studies in animals, damage caused by ischemia can be reversed after infusing healthy mitochondria into injured tissues. An ongoing clinical trial in human hearts at Boston Children's Hospital has also demonstrated that transplanting autologous mitochondria via infusion or direct injection is well-tolerated and safe. The investigators at the University of Washington are recruiting subjects for a first-in-human-brain trial to confirm the safety of autologous mitochondrial transplant during brain ischemia. The transplantation will be performed within the same procedure as the clinically indicated reperfusion treatment. During standard-of-care endovascular treatment for cerebral ischemia, the investigators will obtain a very small biopsy from the muscle tissue adjacent to our surgical access site. Muscle tissue will be processed at bedside to extract the autologous mitochondria as performed in prior human cardiac trial and validated in animal studies. The endovascular treatment proceeds without disruption as clinically indicated, and the mitochondria are infused into the brain artery via micro-catheter during reperfusion.

Official Title
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Study Title: Autologous Mitochondrial Transplant for Cerebral Ischemia

Conditions
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Cerebral Ischemia

Intervention / Treatment
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* Other: Endovascular autologous mitochondrial transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for endovascular thrombectomy to treat acute large vessel occlusion Eligible for angioplasty (microcatheter-based balloon/mechanical and chemical angioplasty) to treat acute cerebral vasospasm after aneurysmal subarachnoid hemorrhage Subjects for whom there is likely to be enough time to obtain meaningful consent from patient or legally-authorized representative Exclusion Criteria: Unable to receive a brain MRI scan Known mitochondrial disease Hemodynamically unstable patients in whom standard of care endovascular reperfusion treatment cannot safely be performed or completed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transplantation<br>Endovascular infusion | Other: Endovascular autologous mitochondrial transplantation<br>* During standard-of-care endovascular reperfusion procedure, subjects will have autologous mitochondria infused via microcatheter into ischemic brain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of severe adverse events during mitochondrial infusion | Cerebral angiography is performed and reviewed in real-time throughout the standard of care reperfusion treatment, including before and after microcatheter infusion of mitochondria. | Through completion of reperfusion therapy, up to one hour post-infusion | 
| Incidence of severe adverse vascular events immediately post-mitochondrial infusion | Post-reperfusion therapy, CT scans are performed as part of the standard of care. The post-procedure CT scan will be reviewed for severe adverse events associated with the microcatheter infusion of mitochondria. | Up to 3 hours post-mitochondrial infusion | 
| Incidence of severe systemic adverse events associated with mitochondrial infusion | Post-reperfusion therapy, peripheral blood studies are performed and reviewed as part of the standard of care to assess systemic function. These include complete blood counts, coagulation studies, and serum chemistry. | Up to seven days after procedure completion | 
| Incidence of severe adverse events related to muscle biopsy | Muscle biopsy is obtained through the same incision as vascular access. The access site is evaluated via physical examination by medical personnel for six hours post-intervention per standard of care protocol. | Up to six hours after procedure completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of infarct volume post-mitochondrial infusion | Patients undergo brain MRI as part of standard of care evaluation after reperfusion therapy. These studies are compared with initial brain imaging studies obtained prior to reperfusion therapy. | Up to seven days after procedure completion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous mitochondrial transplantation, ischemic stroke