Intraarterial Stem Cells in Subacute Ischemic Stroke

To Evaluate the Safety, Feasibility and Clinical Outcome of Intraarterial Infusion of Bone Marrow Derived Mononuclear Cells in Subacute Ischaemic Stroke Patients

Stroke is a leading cause of morbidity and mortality.Acute ischemia causes irreversible damage to neurons and glial cells, leading to functional deficits and chronic sequelae with variable degrees of spontaneous recovery of function. Stem cells have been shown to enhance recovery through multiple immunomodulatory effects, neoangiogenesis and neurogenesis.

We conducted a prospective randomised end observer blinded study to evaluate primarily the safety of intraarterial autologous stem cells delivered to ipsilateral middle cerebral artery in acute and subacute stroke patients (0-15 days post ictus).Secondarily we aimed to evaluate the outcome on the basis of clinical evaluation and follow up imaging

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke; MCA Infarction
• Intervention / Treatment: Biological: autologous BMMNC stem cells; Other: standard care

Detailed Description

1. This study was done over a period of one and a half years from July 2015 to December 2016. A total of 229 patients who presented with acute middle cerebral artery stroke and admitted at Post graduate institute of medical education and research were evaluated for recruitment into this study.
2. Participants who satisfied the inclusion criteria were randomized at 1 week into control and stem cell infusion test group within 15 days of stroke onset.
3. Investigators evaluated 20 patients, with 10 each in control and stem cell infusion test group.
4. Participants in the test group were infused autologous bone marrow mononuclear cells through intraarterial route using a microcatheter which was placed in proximal ipsilateral M1 segment of MCA. Participants in the control group did not receive stem cell therapy. Rest of the pharmacological treatment and physiotherapy were similar in both groups for the period of 6 months.

5,Participants were evaluated with clinical and radiological follow up at 6 months.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Requires presence of all of the following

1. Age range 20-80 years symptoms
2. Signs of clinically definite MCA stroke (0 to 14 days post ictus)
3. National Institute of Health Stroke Scale (NIHSS)> 7,
4. Stroke clinically and on imaging conforming to the MCA territory,
5. Recanalization/patency of involved M1 segment of MCA on imaging
6. Patency of carotid arteries for intra-arterial access of cerebral circulation

Exclusion Criteria: Requires presence of any of the following

1. cerebral hemorrhage on CT/MRI
2. Imaging evidence of M1-MCA segment complete occlusion
3. Hemodynamic instability
4. Known defect of clotting or platelet function
5. Severe co-morbidity precluding intra-arterial intervention
6. Hepatic or renal dysfunction
7. Pregnant patients
8. Patient likely to be unavailable for follow-up
9. Patients with evidence of chronic illness or advanced cancer
10. Patient already dependent in activities of daily living before the present acute stroke i.e. pre stroke mRS >3
11. Refusal to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stem cell group; autologous BMMNC stem cells with standard care	Biological: autologous BMMNC stem cells; Autologous BMMNC injected in the ipsilateral MCA; Other: standard care
Active Comparator: Control; Patients randomised in this group received standard care only	Other: standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in National Institutes of Health Stroke Scale	increase in National Institutes of Health Stroke Scale more than / equal to 4 points	6 month
symptomatic intracranial hemorrhage		6 month
new ischemic lesion		6 month
Death		6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified rankin score	A modified rankin score of 0-1 in patients with National Institutes of Health Stroke Scale of 8-14 at the admission and modified rankin score of 0-2 in patients with National Institutes of Health Stroke Scale >14 at the admission.	6 months

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Investigators: Study Director: Vivek Gupta, DM, Postgraduate Institute of Medical Education and Research; Principal Investigator: Vikas Bhatia, DM, Postgraduate Institute of Medical Education and Research

Publications and helpful links

General Publications

• Moniche F, Gonzalez A, Gonzalez-Marcos JR, Carmona M, Pinero P, Espigado I, Garcia-Solis D, Cayuela A, Montaner J, Boada C, Rosell A, Jimenez MD, Mayol A, Gil-Peralta A. Intra-arterial bone marrow mononuclear cells in ischemic stroke: a pilot clinical trial. Stroke. 2012 Aug;43(8):2242-4. doi: 10.1161/STROKEAHA.112.659409. Epub 2012 Jul 3.
• Battistella V, de Freitas GR, da Fonseca LM, Mercante D, Gutfilen B, Goldenberg RC, Dias JV, Kasai-Brunswick TH, Wajnberg E, Rosado-de-Castro PH, Alves-Leon SV, Mendez-Otero R, Andre C. Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke. Regen Med. 2011 Jan;6(1):45-52. doi: 10.2217/rme.10.97.
• Suarez-Monteagudo C, Hernandez-Ramirez P, Alvarez-Gonzalez L, Garcia-Maeso I, de la Cuetara-Bernal K, Castillo-Diaz L, Bringas-Vega ML, Martinez-Aching G, Morales-Chacon LM, Baez-Martin MM, Sanchez-Catasus C, Carballo-Barreda M, Rodriguez-Rojas R, Gomez-Fernandez L, Alberti-Amador E, Macias-Abraham C, Balea ED, Rosales LC, Del Valle Perez L, Ferrer BB, Gonzalez RM, Bergado JA. Autologous bone marrow stem cell neurotransplantation in stroke patients. An open study. Restor Neurol Neurosci. 2009;27(3):151-61. doi: 10.3233/RNN-2009-0483.
• Savitz SI, Misra V, Kasam M, Juneja H, Cox CS Jr, Alderman S, Aisiku I, Kar S, Gee A, Grotta JC. Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann Neurol. 2011 Jul;70(1):59-69. doi: 10.1002/ana.22458.
• Friedrich MA, Martins MP, Araujo MD, Klamt C, Vedolin L, Garicochea B, Raupp EF, Sartori El Ammar J, Machado DC, Costa JC, Nogueira RG, Rosado-de-Castro PH, Mendez-Otero R, Freitas GR. Intra-arterial infusion of autologous bone marrow mononuclear cells in patients with moderate to severe middle cerebral artery acute ischemic stroke. Cell Transplant. 2012;21 Suppl 1:S13-21. doi: 10.3727/096368912x612512.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: March 7, 2017
• First Submitted That Met QC Criteria: March 14, 2017
• First Posted (Actual): March 15, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2017
• Last Update Submitted That Met QC Criteria: March 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Brain Infarction; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Infarction, Middle Cerebral Artery
• Other Study ID Numbers: PGIMER RADIOLOGY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No