Three stem cell clinical trials for stroke explained – Part III of our Strokemark special report

September 4, 2018

We are all waiting for stem cell treatment to become available. And as we wait, there is actually a lot of work going on to make that happen. To date, several pilot clinical trials have shown that delivering stem cells taken from different sources in different ways (IV, IA, IC; see glossary section for explanation) can be safe. Different studies and clinical trials used stem cells from various sources (see glossary for examples) with positive results.

This video explains what clinical trials are and what you should know before considering participating.

This information might all seem a bit confusing. That’s why we will take the time to explain three current promising studies. All three studies are moving towards becoming Phase III clinical trials, which means that the study will be scaled up so that a greater number of patients can take part. This gives researchers more information so that they can reach more definite conclusions.

Study 1: Pilot Investigation of Human Neural Stem Cells in Chronic Ischemic Stroke Patients (PISCES, NCT01151124) – including the possibility to participate in a new Phase II study within the US (PISCES III)

Phase I

In 2016 researchers from the UK published a Phase I clinical trial in The Lancet. They recruited 11 male patients between 60 and 85 years old to test the safety and tolerability of neural stem cells (cells that come from the nervous system and can regenerate and turn into other types of cells). Patients all had an ischemic stroke 6 months to 5 years ago. ReNeuron Limited, a company that produces the stem cell line CDX-DP which is derived from an embryonic source and used in this study, funded this research. 

Preclinical studies in rats with chronic stroke showed long-term safety, improved behavioral outcomes, and brain tissue regeneration from CDX-DP cells. Because of these positive outcomes, the clinical trial was born. However, the researchers added a component.

The clinical trial aimed to test the same outcomes from the preclinical trials but in humans. And the researchers also wanted to test a dose escalation in chronic stroke patients. Dose escalation means that the number of cells injected became increasingly higher. Progressively, patients received an injection of 2 million, 5 million, 10 million, and then 20 million CTX-DP cells in a single dose directly to the brain. Doctors injected these on the same side the stroke happened, but in healthy brain tissue which provides an environment where the cells can thrive. Researchers then monitored the patients for two years.

The results of this study are promising, showing no adverse effects of stem cell treatment and neurological improvements, as assessed by the National Institute of Health Stroke Scale [NIHSS] score. However, as with most studies, there were limitations like the small sample of only 11 male patients and the wide range of stroke onset before the treatment (6-60 months). Therefore a Phase II study was designed and is now completed.

Phase II

Phase II involved 23 participants who had an ischemic stroke that affected arm movement. Patients all experienced their stroke 2-3 months before participation. All patients received a single dose of 20 million CTX-DP cells. Researchers monitored their progress for one year. The goal was to find evidence for improved arm function. Even though the study was completed recently, no results have been published so far.

However, the results seemed to justify another Phase II study with 110 participants, including a placebo group. And here is the good news: this study will take place in the US (Burlington, Massachusetts). If you are between 35 and 75 years old, your ischemic stroke occurred 4 – 10 months ago (6 – 12 months when the actual surgical procedure starts), and you meet the other criteria listed here (https://clinicaltrials.gov/ct2/show/NCT03629275?term=stem+cells&recrs=ab&cond=stroke&cntry=US&rank=1), you might want to consider showing this your doctor and discuss possible participation.  

Study 2: Phase I/IIa Clinical trial to treat chronic ischemic stroke with mesenchymal cells

Some remarkable discoveries came out of this study involving 18 patients between 30 and 75 years old. All patients were in a chronic state, meaning their stroke was 6 months to 5 years ago. SB623 cells from SanBio, Inc. were injected a few millimeters away from the injury site. It is important not to inject into the injury or too closely because this is not a cell-friendly environment and the implanted cells die very quickly.

This video explains the study with stem cells in stroke.

SB623 cells, which are taken from an adult source, are expected to survive in a cell-friendly environment for up to one month. According to preclinical data, these cells can actively migrate towards the injured area. Each of the 6 patients in each group had either 2.5, 5, or 10 million cells implanted depending on the group assignment. Despite the different amount of cells injected, there were no differences in results between the three groups.

Even though preclinical studies show that stem cells can turn into neurons and form new connections between cells, this study did not support the notion that the more cells injected, the more benefit. Dr. Steinberg hypothesizes the reason for this is that the secreted growth hormones and other factors are responsible for the found effects, not the stem cells themselves.

Limitations and future research

Because this was a Phase I study, there are limitations. There was a small number of patients, group assignment was not random, and there was no placebo group. Also, the patient selection was highly selective. Researchers enrolled less than 5% of all monitored patients. It is important to note that improvements for some patients happened already the day following surgery, which is very early, perhaps maybe too early, for a treatment-related effect. A Phase II study with 156 participants including a placebo group is now actively taking place.

Study 3: STARTING Study: Autologous mesenchymal stem cell transplantation (intravenous) in stroke patients

This study looks at the intravenous infusion of autologous mesenchymal stem cells (aMSCs) in 5 patients and compares them to 25 patients in a control group who did not receive the treatment. Men and women between the ages of 30 and 75 who had an ischemic stroke not more than 90 days ago were included in this study.

So what are aMSCs?

aMSCs are healthy adult stem cells taken from the patient. During a process that takes place in the hospital, technicians harvest these cells. They are cultured and enriched outside the body and then reintroduced back into the patient’s body via an intravenous catheter. These cells secrete growth hormones and other factors. For this reason, researchers expect them to help regenerate and repair a damaged area.

Did aMSCs work?

The researchers found that neurological function improved early on during the therapy. However, those improvements dwindled during the year following the treatment. In fact, most of the improvements disappeared after a year’s time. However, participants reported no adverse effects.

In a follow-up to this study, the researchers monitored 16 patients infused with aMSCs and followed them for 5 years (this group included the 5 patients from the first study). The control group had 36 patients. Again, the participants did not report any adverse effects.

The researchers found that the treated group of patients had a decreased mortality rate and scored better on a modified Rankin scale, which is a standardized scale to measure disabilities. However, the lack of strong statistically significant differences between the groups indicates a need for further research.

Limitations

This study had several limitations. First, there was no placebo group. And the control group knew they did not receive treatment. This can lead to an overestimation of the real effects. Patients might feel better thanks to a strong belief or hope that the treatment helps. It can also lead to exaggerated side-effects for the same reason reversed.

In addition, there was an imbalance between the number of patients in the experimental and control groups. This is a problem for statistics, as the results get less trustworthy with small numbers and invariances. Also, it raises the question as to why so many patients dropped out of the treatment group. Originally, the groups had an equal number of participants. The last limitation considered the usage of aMSCs. Using adult stem cells from your own body has the advantage of reducing possible side effects. However, it takes a while to obtain enough of them in a laboratory procedure. This shifts the treatment away from acute stroke by about 6 weeks due to MSC production procedure.

The physicians running Phase III of the STARTING clinical trial are now recruiting in Korea. They are using a new way to culture the aMSCs and speed up the process. This will reduce the time between stroke and treatment.  

Conclusion

We at Strokemark hope this gives you a better understanding of the current research involving stem cells. The possibilities are exciting and offer patients hope of recovery. If you would like to find out more about these studies, please contact us.

What you can do with this information

Editorial note:

Many clinical trials involving stem cells and stroke recovery exist. Learn about three that show a lot of promise.

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