scholarly journals Are We Ready for Cell Therapy to Treat Stroke?

2021 ◽  
Vol 9 ◽  
Author(s):  
Fernando José Rascón-Ramírez ◽  
Noelia Esteban-García ◽  
Juan Antonio Barcia ◽  
Albert Trondin ◽  
Cristina Nombela ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Therapy ◽  
Statistical Design ◽  
Basic Research ◽  
Phase Iii ◽  
Main Element ◽  
General Description ◽  
Conducting Phase ◽  
Cell Therapies ◽  
Routes Of Administration

Clinical trials of cell therapies that target stroke started at the beginning of this century and they have experienced a significant boost in recent years as a result of promising data from basic research studies. The increase in the information available has paved the way to carry out more innovative and varied human studies. Efforts have focused on the search for a safe and effective treatment to stimulate neuro-regeneration in the brain and to reduce the sequelae of stroke in patients. Therefore, this review aims to evaluate the clinical trials using cell therapy to treat stroke published to date and assess their limitations. From 2000 to date, most of the published clinical trials have focused on phases I or II, and the vast majority of them demonstrate that stem cells are essentially safe to use when administered by different routes, with transient and mild adverse events that do not generally have severe consequences for health. In general, there is considerable variation in the trials in terms of statistical design, sample size, the cells used, the routes of administration, and the functional assessments (both at baseline and follow-up), making it difficult to compare the studies. From this general description, possibly the experimental protocol is the main element to improve in future studies. Establishing an adequate experimental and statistical design will be essential to obtain favorable and reliable results when conducting phase III clinical trials. Thus, it is necessary to standardize the criteria used in these clinical trials in order to aid comparison. Shortly, cell therapy will be a key approach in the treatment of stroke if adequate and comprehensive levels of recovery are to be achieved.

scholarly journals Cell Therapies for Spinal Cord Injury: Trends and Challenges of Current Clinical Trials

Neurosurgery ◽  
2020 ◽  
Vol 87 (4) ◽  
pp. E456-E472
Author(s):  
Richard D Bartlett ◽  
Sarah Burley ◽  
Mina Ip ◽  
James B Phillips ◽  
David Choi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Cell Therapy ◽  
Early Phase ◽  
Basic Research ◽  
Great Promise ◽  
Cell Therapies ◽  
Human Spinal Cord ◽  
Cord Injury

Abstract Cell therapies have the potential to revolutionize the treatment of spinal cord injury. Basic research has progressed significantly in recent years, with a plethora of cell types now reaching early-phase human clinical trials, offering new strategies to repair the spinal cord. However, despite initial enthusiasm for preclinical and early-phase clinical trials, there has been a notable hiatus in the translation of cell therapies to routine clinical practice. Here, we review cell therapies that have reached clinical trials for spinal cord injury, providing a snapshot of all registered human trials and a summary of all published studies. Of registered trials, the majority have used autologous cells and approximately a third have been government funded, a third industry sponsored, and a third funded by university or healthcare systems. A total of 37 cell therapy trials have been published, primarily using stem cells, although a smaller number have used Schwann cells or olfactory ensheathing cells. Significant challenges remain for cell therapy trials in this area, including achieving stringent regulatory standards, ensuring appropriately powered efficacy trials, and establishing sustainable long-term funding. However, cell therapies hold great promise for human spinal cord repair and future trials must continue to capitalize on the exciting developments emerging from preclinical studies.

scholarly journals Progenitor Cell Therapy for the Treatment of Central Nervous System Injury: A Review of the State of Current Clinical Trials

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Peter A. Walker ◽  
Matthew T. Harting ◽  
Shinil K. Shah ◽  
Mary-Clare Day ◽  
Ramy El Khoury ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Progenitor Cell ◽  
Neurological Injury ◽  
Cell Therapies ◽  
Potential Efficacy ◽  
Cord Injury

Recent preclinical work investigating the role of progenitor cell therapies for central nervous system (CNS) injuries has shown potential neuroprotection in the setting of traumatic brain injury (TBI), spinal cord injury (SCI), and ischemic stroke. Mechanisms currently under investigation include engraftment and transdifferentiation, modulation of the locoregional inflammatory milieu, and modulation of the systemic immunologic/inflammatory response. While the exact mechanism of action remains controversial, the growing amount of preclinical data demonstrating the potential benefit associated with progenitor cell therapy for neurological injury warrants the development of well-controlled clinical trials to investigate therapeutic safety and efficacy. In this paper, we review the currently active or recently completed clinical trials investigating the safety and potential efficacy of bone marrow-derived progenitor cell therapies for the treatment of TBI, SCI, and ischemic stroke. Our review of the literature shows that while the preliminary clinical trials reviewed in this paper offer novel data supporting the potential efficacy of stem/progenitor cell therapies for CNS injury, a great deal of additional work is needed to ensure the safety, efficacy, and mechanisms of progenitor cell therapy prior to widespread clinical trials.

scholarly journals Identification of the risks in CAR T-cell therapy clinical trials in China: a Delphi study

2020 ◽  
Vol 12 ◽  
pp. 175883592096657
Author(s):  
Weijia Wu ◽  
Yan Huo ◽  
Xueying Ding ◽  
Yuhong Zhou ◽  
Shengying Gu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
Delphi Method ◽  
Delphi Study ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Aims: Within the past few years, there has been tremendous growth in clinical trials of chimeric antigen receptor (CAR) T-cell therapies. Unlike those of many small-molecule pharmaceuticals, CAR T-cell therapy clinical trials are fraught with risks due to the use of live cell products. The aim of this study is to reach a consensus with experts on the most relevant set of risks that practically occur in CAR T-cell therapy clinical trials. Methods: A Delphi method of consensus development was used to identify the risks in CAR T-cell therapy clinical trials, comprising three survey rounds. The expert panel consisted of principal investigators, clinical research physicians, members of institutional ethics committees, and Good Clinical Practice managers. Results: Of the 24 experts invited to participate in this Delphi study, 20 participants completed Round 1, Round 2, and Round 3. Finally, consensus (defined as >80% agreement) was achieved for 54 risks relating to CAR T-cell clinical trials. Effective interventions related to these risks are needed to ensure the proper protection of subject health and safety. Conclusion: The Delphi method was successful in gaining a consensus on risks relevant to CAR T-cell clinical trials in a geographically diverse expert association. It is hoped that this work can benefit future risk-based quality management in clinical trials and can potentially promote the better development of CAR T-cell therapy products.

scholarly journals Trends in clinical trials for stroke by cell therapy: data mining ClinicalTrials.gov and the ICTRP portal site

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Takaharu Negoro ◽  
Hanayuki Okura ◽  
Midori Maehata ◽  
Shigekazu Hayashi ◽  
Satoru Yoshida ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Therapy ◽  
Chronic Phase ◽  
Cell Types ◽  
Phase Iii ◽  
Definitive Treatment ◽  
Stroke Treatment ◽  
Portal Site ◽  
Therapy Studies ◽  
Phase Iii Studies

Abstract Definitive treatment of stroke constitutes an important thesis of regenerative medicine in the cerebrovascular field. However, to date, no cell therapy products for stroke are yet on the market. In this study, we examined the clinical research trends related to cell therapy products in the stroke field based on data obtained from the ClinicalTrials.gov website and International Clinical Trials Research Platform (ICTRP) portal site. These data do not offer results of clinical trials comprehensively but provide information regarding various attributes of planned clinical trials including work in progress. We selected 78 cell therapy studies related to the field of stroke treatment from ClinicalTrial.gov and ICTRP. These were analyzed according to, e.g., the reporting countries, origin (autologous or allogeneic), of cell used, cell types and source organs, the progress of translational phases, target phase of the disease (acute or chronic stroke), and route of administration. This analysis revealed a trend whereby in the acute phase, mesenchymal stem cells were administered intravenously at a relatively higher dose, whereas in the chronic phase a small number of cells were administered intracranially. Only two randomized controlled Phase III studies with over 100 patients are registered, but none of them has been completed. Thus, cell therapy against stroke appears to constitute a premature area compared with cartilage repair as assessed in our previous report. In addition, tracking by means of the ID number of each trial via PubMed revealed that 44% of clinical studies in this field have corresponding published results, which was also discussed.

scholarly journals Cardiac Cell Therapies for the Treatment of Acute Myocardial Infarction: A Meta-Analysis from Mouse Studies

2017 ◽  
Vol 42 (1) ◽  
pp. 254-268 ◽  
Author(s):  
Cajetan Immanuel Lang ◽  
Markus Wolfien ◽  
Anne Langenbach ◽  
Paula Müller ◽  
Olaf Wolkenhauer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Mouse Model ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cell Therapies ◽  
Positive Effects ◽  
Advanced Therapies

Aims: Stem cell-based regenerative therapies for the treatment of ischemic myocardium are currently a subject of intensive investigation. A variety of cell populations have been demonstrated to be safe and to exert some positive effects in human Phase I and II clinical trials, however conclusive evidence of efficacy is still lacking. While the relevance of animal models for appropriate pre-clinical safety and efficacy testing with regard to application in Phase III studies continues to increase, concerns have been expressed regarding the validity of the mouse model to predict clinical results. Against the background that hundreds of preclinical studies have assessed the efficacy of numerous kinds of cell preparations - including pluripotent stem cells - for cardiac repair, we undertook a systematic re-evaluation of data from the mouse model, which initially paved the way for the first clinical trials in this field. Methods and Results: A systematic literature screen was performed to identify publications reporting results of cardiac stem cell therapies for the treatment of myocardial ischemia in the mouse model. Only peer-reviewed and placebo-controlled studies using magnet resonance imaging (MRI) for left ventricular ejection fraction (LVEF) assessment were included. Experimental data from 21 studies involving 583 animals demonstrate a significant improvement in LVEF of 8.59%+/- 2.36; p=.012 (95% CI, 3.7–13.8) compared with control animals. Conclusion: The mouse is a valid model to evaluate the efficacy of cell-based advanced therapies for the treatment of ischemic myocardial damage. Further studies are required to understand the mechanisms underlying stem cell based improvement of cardiac function after ischemia.

scholarly journals Stem cell therapies for ischemic stroke: current animal models, clinical trials and biomaterials

RSC Advances ◽  
2017 ◽  
Vol 7 (30) ◽  
pp. 18668-18680 ◽  
Author(s):  
Hugh H. Chan ◽  
Connor A. Wathen ◽  
Ming Ni ◽  
Shuangmu Zhuo
Keyword(s):  
Tissue Engineering ◽  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Animal Models ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Stem Cell Therapies ◽  
Cell Therapies

We report the facilitation of stem cell therapy in stroke by tissue engineering and applications of biomaterials.

scholarly journals Cell therapies for traumatic brain injury

2008 ◽  
Vol 24 (3-4) ◽  
pp. E18 ◽  
Author(s):  
Matthew T. Harting ◽  
James E. Baumgartner ◽  
Laura L. Worth ◽  
Linda Ewing-Cobbs ◽  
Adrian P. Gee ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Clinical Trials ◽  
Brain Injury ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Current Status ◽  
Cell Therapies ◽  
Current Therapies

Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease. Traumatic brain injury is a devastating event for which current therapies are limited. In this report the authors discuss the current status of using adult stem cells to treat traumatic brain injury, including the basic cell types and potential mechanisms of action, preclinical data, and the initiation of clinical trials.

scholarly journals Monitoring in practice – How are UK academic clinical trials monitored? A survey

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sharon B. Love ◽  
Victoria Yorke-Edwards ◽  
Sarah Lensen ◽  
Matthew R. Sydes
Keyword(s):  
Clinical Trials ◽  
Online Survey ◽  
Research Collaboration ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Final Decision ◽  
Evidence Based ◽  
Conducting Phase ◽  
Central Monitoring ◽  
Site Monitoring

Abstract Background Despite the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) encouraging the use of risk-based monitoring for trials in 2013, there remains a lack of evidence-based guidelines on how to monitor. We surveyed the academic United Kingdom Clinical Research Collaboration (UKCRC) registered clinical trials units (CTUs) to find out their policy on monitoring of phase III randomised clinical trials of an investigational medicinal product (CTIMPs). Methods An online survey of monitoring policy with sections on the CTU, central monitoring and on-site monitoring was sent to all 50 UKCRC registered CTUs in November 2018. Descriptive data analysis and tabulations are reported using the total number answering each question. Results A total of 43/50 (86%) of CTUs responded with 38 conducting phase III randomised CTIMP trials. Of these 38 CTUs, 34 finished the survey. Most CTUs (36/37, 97%) use a central monitoring process to guide, target or supplement site visits. More than half (19/36, 53%) of CTUs do not use an automated monitoring report when centrally monitoring trials and all units use trial team knowledge to make a final decision on whether an on-site visit is required. A total of 31/34 (91%) CTUs used triggers to decide whether or not to conduct an on-site monitoring visit. On-site, a mixture of source data verification and checking of processes was carried out. The CTUs overwhelmingly (27/34, 79%) selected optimising central monitoring as their most pressing concern. Conclusion The survey showed a wide variation in phase III randomised CTIMP trial monitoring practices by academic clinical trials units within a single research-active country. We urgently need to develop evidence-based regulator-agreed guidance for CTUs on best practice for both central and on-site monitoring and to develop tools for all CTUs to use.

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