Abstract
BackgroundRecovery after a major stroke is usually limited, but cell therapy for patients with fixed neurologic deficits is emerging. Several recent clinical trials have investigated mesenchymal stem cell (MSC) therapy for patients with ischemic stroke. We previously reported the results of a controlled trial on the application of autologous MSCs in patients with ischemic stroke with a long-term follow-up of up to 5 years (the 'STem cell Application Researches and Trials In NeuroloGy’ (STARTING) study). The results from this pilot trial are challenging, but also raise important issues. In addition, there have been recent efforts to improve the safety and efficacy of MSC therapy for stroke.Methods and designThe clinical and preclinical background and the STARTING-2 study protocol are provided. The trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial. Both acute and chronic stroke patients will be selected based on clinical and radiological features and followed for 3 months after MSC treatment. The subjects will be randomized into one of two groups: (A) a MSC group (n = 40) or (B) a control group (n = 20). Autologous MSCs will be intravenously administered after ex vivo culture expansion with autologous ischemic serum obtained as early as possible, to enhance the therapeutic efficacy (ischemic preconditioning). Objective outcome measurements will be performed using multimodal MRI and detailed functional assessments by blinded observers.DiscussionThis trial is the first to evaluate the efficacy of MSCs in patients with ischemic stroke. The results may provide better evidence for the effectiveness of MSC therapy in patients with ischemic stroke.Trial registrationThis trial was registered with ClinicalTrials.gov, number NCT01716481.
Highlights
Recovery after a major stroke is usually limited, but cell therapy for patients with fixed neurologic deficits is emerging
This trial is the first to evaluate the efficacy of mesenchymal stem cell (MSC) in patients with ischemic stroke
Enhancing the therapeutic effects of stem cells Limited efficacy of current MSC therapy strategies The Cochrane group recently assessed the efficacy and safety of stem cell transplantation compared with conventional treatments in patients with ischemic stroke [40]
Summary
The STARTING-2 trial Trial characteristics and design STARTING-2 is the first study to evaluate the efficacy of MSC treatment in patients with ischemic stroke. Study objectives The study tests the hypothesis that patients with ischemic stroke with moderate to severe persistent neurologic deficits will have better outcomes with intravenous transplantation of autologous MSCs expanded with autologous serum obtained during the acute phase of stroke than patients receiving standard treatment. Any evidence of chronic comorbid condition or unstable acute systemic illnesses which, in the investigator’s opinion, could shorten survival or limit ability to complete the study 5 Presence of HIV, HBV, HCV, or syphilis on admission blood tests 6 Presence of active depression not adequately controlled that interferes with major activities of daily living immediately prior to the current stroke 7 Presence of dementia prior to the current stroke that is likely to confound clinical evaluation 8 Lactating women or pregnant women as determined by positive urine hCG test 9 Considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol 10 Unwilling to undergo bone marrow aspiration aWe will measure the degree of involvement of the ipsilateral subventricular zone on the initial diffusion-weighted image at two axial levels; (a) the upper thalamus and head of caudate nucleus and (b) the corona radiate (7-mm upper level).
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