Limits...
Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial.

Kim SJ, Moon GJ, Chang WH, Kim YH, Bang OY, STARTING-2 (STem cell Application Researches and Trials In NeuroloGy-2) collaborato - Trials (2013)

Bottom Line: The clinical and preclinical background and the STARTING-2 study protocol are provided.The subjects will be randomized into one of two groups: (A) a MSC group (n = 40) or (B) a control group (n = 20).Objective outcome measurements will be performed using multimodal MRI and detailed functional assessments by blinded observers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Gangnam-gu, Seoul, South Korea. nmboy@unitel.co.kr.

ABSTRACT

Background: Recovery 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 design: The 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.

Discussion: This 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 registration: This trial was registered with ClinicalTrials.gov, number NCT01716481.

Show MeSH

Related in: MedlinePlus

Study protocol of 'STem cell Application Researches and Trials In NeuroloGy-2’ (STARTING-2) study at each timepoint. *Indicates 1 day before mesenchymal stem cell (MSC) infusion in the MSC group vs 30 days (± 2 days) after randomization in the control group. †MSC group only. ‡Will be performed at 14 days after MSC transplantation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4016561&req=5

Figure 3: Study protocol of 'STem cell Application Researches and Trials In NeuroloGy-2’ (STARTING-2) study at each timepoint. *Indicates 1 day before mesenchymal stem cell (MSC) infusion in the MSC group vs 30 days (± 2 days) after randomization in the control group. †MSC group only. ‡Will be performed at 14 days after MSC transplantation.

Mentions: The clinical trial protocol and consent form were approved by the Korean FDA and the Institutional Review Board of the Samsung Medical Center. Written informed consent will be obtained from all patients and/or their first-degree relatives. Inclusion and exclusion criteria are shown in Table 2. During the inpatient rehabilitation period, all participants will receive conventional rehabilitation therapy (physical, occupational, speech/language, or cognitive rehabilitation therapy as needed). Investigators blinded to treatment allocation will measure neurological disability using the NIHSS and functional scores for mRS and mBI. Motor parameters will be evaluated by the Motricity index and Fugl-Meyer assessment for gross motor function, Purdue pegboard test and box and block test for fine motor function, and functional ambulatory category and 10-m gait speed tests for mobility, for further demonstration and characterization of motor recovery [56-60]. Cognition (Mini-Mental Status Examination (MMSE)) and quality of life (EuroQol Five Dimensions (EQ-5D) questionnaire) tests will also be administered. Any complications or adverse effects observed during the study period will be described in detail. Flow diagrams of the study protocol are shown in Figures 2 and 3.


Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial.

Kim SJ, Moon GJ, Chang WH, Kim YH, Bang OY, STARTING-2 (STem cell Application Researches and Trials In NeuroloGy-2) collaborato - Trials (2013)

Study protocol of 'STem cell Application Researches and Trials In NeuroloGy-2’ (STARTING-2) study at each timepoint. *Indicates 1 day before mesenchymal stem cell (MSC) infusion in the MSC group vs 30 days (± 2 days) after randomization in the control group. †MSC group only. ‡Will be performed at 14 days after MSC transplantation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016561&req=5

Figure 3: Study protocol of 'STem cell Application Researches and Trials In NeuroloGy-2’ (STARTING-2) study at each timepoint. *Indicates 1 day before mesenchymal stem cell (MSC) infusion in the MSC group vs 30 days (± 2 days) after randomization in the control group. †MSC group only. ‡Will be performed at 14 days after MSC transplantation.
Mentions: The clinical trial protocol and consent form were approved by the Korean FDA and the Institutional Review Board of the Samsung Medical Center. Written informed consent will be obtained from all patients and/or their first-degree relatives. Inclusion and exclusion criteria are shown in Table 2. During the inpatient rehabilitation period, all participants will receive conventional rehabilitation therapy (physical, occupational, speech/language, or cognitive rehabilitation therapy as needed). Investigators blinded to treatment allocation will measure neurological disability using the NIHSS and functional scores for mRS and mBI. Motor parameters will be evaluated by the Motricity index and Fugl-Meyer assessment for gross motor function, Purdue pegboard test and box and block test for fine motor function, and functional ambulatory category and 10-m gait speed tests for mobility, for further demonstration and characterization of motor recovery [56-60]. Cognition (Mini-Mental Status Examination (MMSE)) and quality of life (EuroQol Five Dimensions (EQ-5D) questionnaire) tests will also be administered. Any complications or adverse effects observed during the study period will be described in detail. Flow diagrams of the study protocol are shown in Figures 2 and 3.

Bottom Line: The clinical and preclinical background and the STARTING-2 study protocol are provided.The subjects will be randomized into one of two groups: (A) a MSC group (n = 40) or (B) a control group (n = 20).Objective outcome measurements will be performed using multimodal MRI and detailed functional assessments by blinded observers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Gangnam-gu, Seoul, South Korea. nmboy@unitel.co.kr.

ABSTRACT

Background: Recovery 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 design: The 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.

Discussion: This 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 registration: This trial was registered with ClinicalTrials.gov, number NCT01716481.

Show MeSH
Related in: MedlinePlus