Autologous Mitochondrial Transplant for Cerebral Ischemia

NCT04998357 | Recruiting DMC

• 1 other identifier: STUDY00006638
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cerebral Ischemia

Keywords

autologous mitochondrial transplantation; ischemic stroke

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Reduction of infarct volume post-mitochondrial infusion

  Up to seven days after procedure completion.

Study Arms (1)

Transplantation

EXPERIMENTAL

Endovascular infusion

Other: Endovascular autologous mitochondrial transplantation

Interventions

Endovascular autologous mitochondrial transplantation OTHER

During standard-of-care endovascular reperfusion procedure, subjects will have autologous mitochondria infused via microcatheter into ischemic brain.

Transplantation

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Harborview Medical Center

Seattle, Washington, 98104, United States

RECRUITING

Related Publications (16)

• Miralles FJ, Prijoles KL, Winter A, Levitt MR, Sancak Y, Walker M. Periprocedural therapeutics do not impair extracellular mitochondrial viability in transplantation. J Cereb Blood Flow Metab. 2025 May 14:271678X251340232. doi: 10.1177/0271678X251340232. Online ahead of print.

  PMID: 40367391 BACKGROUND

• Walker, M., Federico, E., Sancak, Y. et al. Mitochondrial Transplantation in Ischemic Stroke: Insights from a First-in-Human Brain Trial. Curr Transpl Rep 11, 53-62 (2024). https://doi.org/10.1007/s40472-024-00428-6

  BACKGROUND

• Walker M, Levitt MR, Federico EM, Miralles FJ, Levy SH, Lynne Prijoles K, Winter A, Swicord JK, Sancak Y. Autologous mitochondrial transplant for acute cerebral ischemia: Phase 1 trial results and review. J Cereb Blood Flow Metab. 2024 Dec 4:271678X241305230. doi: 10.1177/0271678X241305230. Online ahead of print.

  PMID: 39628322 BACKGROUND

• Preble JM, Pacak CA, Kondo H, MacKay AA, Cowan DB, McCully JD. Rapid isolation and purification of mitochondria for transplantation by tissue dissociation and differential filtration. J Vis Exp. 2014 Sep 6;(91):e51682. doi: 10.3791/51682.

  PMID: 25225817 BACKGROUND

• Guariento A, Piekarski BL, Doulamis IP, Blitzer D, Ferraro AM, Harrild DM, Zurakowski D, Del Nido PJ, McCully JD, Emani SM. Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury. J Thorac Cardiovasc Surg. 2021 Sep;162(3):992-1001. doi: 10.1016/j.jtcvs.2020.10.151. Epub 2020 Dec 1.

  PMID: 33349443 BACKGROUND

• Weixler V, Lapusca R, Grangl G, Guariento A, Saeed MY, Cowan DB, Del Nido PJ, McCully JD, Friehs I. Autogenous mitochondria transplantation for treatment of right heart failure. J Thorac Cardiovasc Surg. 2021 Jul;162(1):e111-e121. doi: 10.1016/j.jtcvs.2020.08.011. Epub 2020 Aug 10.

  PMID: 32919774 BACKGROUND

• Doulamis IP, Guariento A, Duignan T, Kido T, Orfany A, Saeed MY, Weixler VH, Blitzer D, Shin B, Snay ER, Inkster JA, Packard AB, Zurakowski D, Rousselle T, Bajwa A, Parikh SM, Stillman IE, Del Nido PJ, McCully JD. Mitochondrial transplantation by intra-arterial injection for acute kidney injury. Am J Physiol Renal Physiol. 2020 Sep 1;319(3):F403-F413. doi: 10.1152/ajprenal.00255.2020. Epub 2020 Jul 20.

  PMID: 32686525 BACKGROUND

• Orfany A, Arriola CG, Doulamis IP, Guariento A, Ramirez-Barbieri G, Moskowitzova K, Shin B, Blitzer D, Rogers C, Del Nido PJ, McCully JD. Mitochondrial transplantation ameliorates acute limb ischemia. J Vasc Surg. 2020 Mar;71(3):1014-1026. doi: 10.1016/j.jvs.2019.03.079. Epub 2019 Jul 26.

  PMID: 31353269 BACKGROUND

• Ramirez-Barbieri G, Moskowitzova K, Shin B, Blitzer D, Orfany A, Guariento A, Iken K, Friehs I, Zurakowski D, Del Nido PJ, McCully JD. Alloreactivity and allorecognition of syngeneic and allogeneic mitochondria. Mitochondrion. 2019 May;46:103-115. doi: 10.1016/j.mito.2018.03.002. Epub 2018 Mar 26.

  PMID: 29588218 BACKGROUND

• McCully JD, Levitsky S, Del Nido PJ, Cowan DB. Mitochondrial transplantation for therapeutic use. Clin Transl Med. 2016 Mar;5(1):16. doi: 10.1186/s40169-016-0095-4. Epub 2016 Apr 29.

  PMID: 27130633 BACKGROUND

• Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, Ji X, Lo EH. Transfer of mitochondria from astrocytes to neurons after stroke. Nature. 2016 Jul 28;535(7613):551-5. doi: 10.1038/nature18928.

  PMID: 27466127 BACKGROUND

• Pluchino S, Peruzzotti-Jametti L, Frezza C. Astrocyte power fuels neurons during stroke. Swiss Med Wkly. 2016 Nov 10;146:w14374. doi: 10.4414/smw.2016.14374. eCollection 2016. No abstract available.

  PMID: 27878792 BACKGROUND

• Bambrick L, Kristian T, Fiskum G. Astrocyte mitochondrial mechanisms of ischemic brain injury and neuroprotection. Neurochem Res. 2004 Mar;29(3):601-8. doi: 10.1023/b:nere.0000014830.06376.e6.

  PMID: 15038607 BACKGROUND

• Wu M, Gu X, Ma Z. Mitochondrial Quality Control in Cerebral Ischemia-Reperfusion Injury. Mol Neurobiol. 2021 Oct;58(10):5253-5271. doi: 10.1007/s12035-021-02494-8. Epub 2021 Jul 18.

  PMID: 34275087 BACKGROUND

• Norat P, Soldozy S, Sokolowski JD, Gorick CM, Kumar JS, Chae Y, Yagmurlu K, Prada F, Walker M, Levitt MR, Price RJ, Tvrdik P, Kalani MYS. Mitochondrial dysfunction in neurological disorders: Exploring mitochondrial transplantation. NPJ Regen Med. 2020 Nov 23;5(1):22. doi: 10.1038/s41536-020-00107-x.

  PMID: 33298971 BACKGROUND

• Norat P, Sokolowski JD, Gorick CM, Soldozy S, Kumar JS, Chae Y, Yagmurlu K, Nilak J, Sharifi KA, Walker M, Levitt MR, Klibanov AL, Yan Z, Price RJ, Tvrdik P, Kalani MYS. Intraarterial Transplantation of Mitochondria After Ischemic Stroke Reduces Cerebral Infarction. Stroke Vasc Interv Neurol. 2023 May;3(3):e000644. doi: 10.1161/svin.122.000644. Epub 2023 Mar 2.

  PMID: 37545759 BACKGROUND

Related Links

• The Stroke \& Applied NeuroScience Center at the University of Washington

MeSH Terms

Conditions

Brain Ischemia; Ischemic Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke

Study Officials

• Melanie S Walker, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

206-897-5802; sanslab@uw.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, School of Medicine

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: August 10, 2021
• Study Start: April 29, 2021
• Primary Completion: April 29, 2026
• Study Completion (Estimated): October 29, 2026
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)