The PISCES I study was conducted in Scotland at the Institute of Neurological Sciences, Southern General Hospital, Greater Glasgow and Clyde NHS Board. In this single administration, dose escalation safety study, ReNeuron’s CTX stem cell therapy was administered in ascending doses to a total of 11 stroke patients who were left disabled by an ischaemic stroke, the most common form of the condition. The Principal Investigator for the PISCES I trial was Professor Keith Muir, SINAPSE Professor of Clinical Imaging, Division of Clinical Neurosciences at the University of Glasgow. The aim of the clinical trial was to evaluate the safety of the implantation technique and to establish the side effect profile associated with the implantation of ReNeuron’s CTX stem cell therapy in patients who have suffered an ischaemic stroke.
Patients in the Phase I study were initially followed-up for at least two years. The two year end-point has now passed and they are continuing to be monitored in the longer term. Although the primary endpoints of the clinical trial relate to the safety and tolerability of the treatment, a number of clinical assessments of the patients in the trial are being made to evaluate changes in both motor and cognitive function over time.
In April 2015, long term follow-up data out to at least 24 months in all patients treated in the PISCES study was presented by the clinical team from Glasgow’s Southern General Hospital in a platform presentation at the 2015 European Stroke Organisation Conference (ESOC), taking place in Glasgow.
There have been no cell-related or immunological adverse events reported in any of the eleven patients treated in the study (across the four ascending dose levels). Adverse events reported were related only to the implantation procedure or the patient’s underlying medical condition.
Improvements in neurological status and limb function compared to pre-treatment baseline performance were observed within three months of treatment and maintained throughout long term follow-up. Improvements in the National Institutes of Health Stroke Scale (NIHSS) were seen in all dose groups. The NIHSS is a measure used to objectively quantify the impairment caused by a stroke. For all subjects, the median baseline score was 7. This improved to 5 at 3 months and was sustained at 2 years follow up with a median score of 5 (p=0.002).
Other measures of neuromuscular disability were supportive of the NIHSS improvement. Mean Ashworth Scale scores, a measure of limb spasticity, were 18.1 and 9.7 (affected upper and lower limb, respectively) at baseline, which improved to 15.7 and 7.8 at 3 months and 16.1 and 6.5 at 2 years. Improvements in scores on the Barthel Index (a measure of activities of daily living) were also consistent with the neuromuscular score changes with a median value of 12 at baseline, 14 at 3 months and 14 at 2 years.
In May 2014, long term follow up data to 12 months in all 11 patients treated in the PISCES study were presented by the clinical team from Glasgow’s Southern General Hospital at the 23rd European Stroke Conference in Nice, France.
There were no cell-related or immunological adverse events reported in any of the patients treated in the study. Adverse events were related only to the implantation procedure or underlying co-morbidities. Sustained reductions in neurological impairment and spasticity were observed in most patients compared to their stable pre-treatment baseline performance, reflected in the summary evaluation scores below (n=11 patients):
- National Institutes of Health Stroke Scale (measure of neurological deficit):
Trial inclusion criteria require a score of 6 or more, representing stable moderate to severe disability (total of 2 or more for motor arm and leg scores):
o Median pre-treatment score = 7
o Post-treatment scores improved by median 2 points at 3 months and 3 points at 12 months
- Barthel Index (measure of independence in performing activities of daily living, rated 0- 20):
o Median pre-treatment score = 12
o Post-treatment scores improved by median 1 point at 3 months and 3 points at 12 months
- Summated Ashworth Score (aggregated measure of spasticity in affected limbs, rated 0-40 arm, 0-25 leg):
o Mean pre-treatment aggregate score = 29
o Post-treatment scores improved by mean 5 points at 3 months and 7 points at 12 months
- Modified Rankin Score (overall measure of disability and handicap, rated 0-6):
o Median pre-treatment score = 3
o Score improved by 1 grade in n=4/11 patients at 12 months, with n=7/11 patients unchanged
- EuroQOL score (quality of life outcome measure, rated 0-100):
o Median pre-treatment score = 45
o Post-treatment scores improved by median 18 points at 12 months.
Preliminary functional MRI data in 7 of the treated patients at resting state show, at a group level, evidence of increased short-term connectivity between the cell-implanted region of the brain (the putamen) and the other deep brain regions that are concerned with sensory motor control, although relevance to functional outcomes in the patients requires further evaluation.
Further information regarding our clinical trials, including relevant contact details, may be found on clinicaltrials.gov.