StrokePhase 1PISCESNCT01151124
Pilot Investigation of Stem Cells in Stroke
A Phase 1 study testing CTX0E03 neural stem cells in people with Stroke, run by ReNeuron Limited at 1 site in United Kingdom.
Trial summary
The study is designed to test the safety of a manufactured neural stem cell line (CTX cells) delivered by injection into the damaged brains of male patients 60 years of age or over who remain moderately to severely disabled 6 months to 5 years following an ischemic stroke. Read more about this study
- Who is it for?
- Ages 60 to 85 years, men only
- Conditions the study is for
- Stroke
- What is being tested?
- CTX0E03 neural stem cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2010to Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males
- 60 years or over
- Unilateral ischemic stroke involving subcortical white matter or Basal Ganglia 6 months to 5 years before entry
- NIHSS score minimum 6 with hemiparesis (2 or more for motor arm and leg)
- Neurologically stable for 2 m
- modified Rankin score of 2-4
Show all 9Show fewer
- Fit for general anesthesia, neurosurgery
- Capacity to consent
- Infarct at least 1cm diameter
Who cannot join
- Structural brain vascular lesions requiring surgery or increasing the risk of stereotaxic implantation
- Unstable medical conditions with expected survival <12 months
- Any medical condition that would impair participation (eg progressive neurological disorders, mental illness)
- Major surgery within 30 days
- Previous allogeneic tissue transplant
- MMSE < 24
Show all 10Show fewer
- Epilepsy
- Coagulation disorders or anticoagulant treatment that cannot be interrupted
- Stimulants, botox, tamoxifen
- Contraindications to MRI
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Division of Clinical Neurosciences, Glasgow Southern General Hospital
Glasgow, G51 4TF
About this study
Official title: A Phase I Safety Trial of CTX0E03 Drug Product Delivered Intracranially in the Treatment of Patients With Stable Ischemic Stroke
The study is designed to test the safety of a manufactured neural stem cell line (CTX cells) delivered by injection into the damaged brains of male patients 60 years of age or over who remain moderately to severely disabled 6 months to 5 years following an ischemic stroke. In addition the trial will evaluate a range of potential efficacy measures for future trials. Treatment will involve a single injection of one of four doses of CTX cells into the patient's brain in a carefully controlled neurosurgical operation performed under general anesthetic. The trial is designed to treat 12 patients and measure outcomes over 24 months. Patients will be invited to participate in a long-term follow-up trial for a further 8 years.
Read the detailed description
Design: The trial is an open label, single administration, ascending dose, single site trial using CTX neural stem cells with 24-month patient monitoring following treatment.
Pre-treatment selection of patients : Males aged ≥60 years with unilateral ischaemic stroke affecting sub-cortical white matter and/or basal ganglia 6 months to 5 years prior to entry into the study, with persistent unilateral hemiparesis, a minimum infarct diameter of 1 cm and stable neurological functional deficit as determined by the NIH Stroke Scale, (measured twice at least 1 month apart), will be eligible for treatment.
Treatment: The CTX cells will be injected by stereotaxic procedures into the putamen region of the brain of the patient under general anesthesia with imaging guidance to locate injection site. Four ascending doses of CTX cells will be tested in 12 patients (4 dosage groups of three patients at each dose level receiving 2 million, 5 million, 10 million or 20 million cells). Patients will be admitted to hospital the day before surgery and prepared for CTX cell implantation to take place. Patients will be discharged two days after surgery.
One patient will be treated at a time. An independent Data Safety Monitoring Board (DSMB) will make the decision to continue dosing at each dose level following satisfactory review of the 28 day safety data for the first patient at that dose level; and to increase the dose to the next level following satisfactory review of the 3 month safety data for all three patients in the previous dose group.
Post treatment follow-up of patients: There will be 6 scheduled visits to clinic for monitoring and neurofunctional testing and 5 scheduled telephone contacts to monitor adverse events (AEs) and concomitant medications over the 2 year follow-up period.
End-points: The primary end-point of the trial is safety, measured by numbers of relevant Serious Adverse Events, health screening, neurological assessment and scanning abnormalities. The secondary aim is to evaluate various MRI and other test measures for their potential as efficacy markers for subsequent trials.
Post trial follow up: All trial patients will be flagged by the National Health Service Central Register (NHSCR) Scotland for life-long follow-up. In addition, all patients will be invited to take part in an 8-year follow up trial requiring an annual review by a suitable physician.
- Conditions
- Stroke
- Being tested
- CTX0E03 neural stem cells
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTX0E03 neural stem cellsBiological
Single administration by surgical delivery to the damaged area of the brain
| Study group | Role | What they receive |
|---|---|---|
| CTX0E03 DP | Experimental | human neural stem cell product, once only injection, increasing doses Receives: Biological: CTX0E03 neural stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
AEs monitored include vital signs, C-reactive protein and full blood count, structural MRI to seek evidence of hemorrhage, new infarction, inflammation or tumor, NIHSS measure (changes greater than 4) to indicate clinically significant neurological deterioration, neurological examination, CTX0E03 antibody screen, changes to concomitant medications
Measured: 1 year
Secondary outcomes (4)
Barthel Index
Measure of functional outcome (based on activities of daily living)
Measured: 1 year
Mini-Mental State Examination
Measure of cognitive impairment
Measured: 1 year
modified Rankin Score
Measure of overall disability and handicap
Measured: 1 year
EQ-5D
Measure of health-related quality of life outcomes
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2010 (estimated)
- Study startJun 2010
- Primary completionOct 2012
- Study completionOct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- ReNeuron Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01151124
- Sponsor's protocol ID
- RN01-CP-0001
- Acronym
- PISCES
- Status last verified
- Jul 2023
- First submitted
- 9 Jun 2010
- Last updated
- 6 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kalladka D, Sinden J, Pollock K, Haig C, McLean J, Smith W, McConnachie A, Santosh C, Bath PM, Dunn L, Muir KW. Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. Lancet. 2016 Aug 20;388(10046):787-96. doi: 10.1016/S0140-6736(16)30513-X. Epub 2016 Aug 3.
PubMed 27497862Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD. Investigation of Content, Stoichiometry and Transfer of miRNA from Human Neural Stem Cell Line Derived Exosomes. PLoS One. 2016 Jan 11;11(1):e0146353. doi: 10.1371/journal.pone.0146353. eCollection 2016.
PubMed 26752061Stevanato L, Hicks C, Sinden JD. Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes. J Vis Exp. 2015 Apr 12;(98):52410. doi: 10.3791/52410.
PubMed 25938519Stevanato L, Sinden JD. The effects of microRNAs on human neural stem cell differentiation in two- and three-dimensional cultures. Stem Cell Res Ther. 2014 Apr 11;5(2):49. doi: 10.1186/scrt437.
PubMed 24725992
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Safety Trial of CTX0E03 Drug Product Delivered Intracranially in the Treatment of Patients With Stable Ischemic Stroke
- ClinicalTrials.gov ID
- NCT01151124
- Acronym / sponsor ID
- PISCES / RN01-CP-0001
- Conditions
- Stroke
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- ReNeuron LimitedIndustry (pharma, biotech, devices)
- Study start
- Jun 2010 (actual)
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2022 (actual)
- First posted
- 25 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is designed to test the safety of a manufactured neural stem cell line (CTX cells) delivered by injection into the damaged brains of male patients 60 years of age or over who remain moderately to severely disabled 6 months to 5 years following an ischemic stroke. In addition the trial will evaluate a range of potential efficacy measures for future trials. Treatment will involve a single injection of one of four doses of CTX cells into the patient's brain in a carefully controlled neurosurgical operation performed under general anesthetic. The trial is designed to treat 12 patients and measure outcomes over 24 months. Patients will be invited to participate in a long-term follow-up trial for a further 8 years.
Detailed description
Design: The trial is an open label, single administration, ascending dose, single site trial using CTX neural stem cells with 24-month patient monitoring following treatment.
Pre-treatment selection of patients : Males aged ≥60 years with unilateral ischaemic stroke affecting sub-cortical white matter and/or basal ganglia 6 months to 5 years prior to entry into the study, with persistent unilateral hemiparesis, a minimum infarct diameter of 1 cm and stable neurological functional deficit as determined by the NIH Stroke Scale, (measured twice at least 1 month apart), will be eligible for treatment.
Treatment: The CTX cells will be injected by stereotaxic procedures into the putamen region of the brain of the patient under general anesthesia with imaging guidance to locate injection site. Four ascending doses of CTX cells will be tested in 12 patients (4 dosage groups of three patients at each dose level receiving 2 million, 5 million, 10 million or 20 million cells). Patients will be admitted to hospital the day before surgery and prepared for CTX cell implantation to take place. Patients will be discharged two days after surgery.
One patient will be treated at a time. An independent Data Safety Monitoring Board (DSMB) will make the decision to continue dosing at each dose level following satisfactory review of the 28 day safety data for the first patient at that dose level; and to increase the dose to the next level following satisfactory review of the 3 month safety data for all three patients in the previous dose group.
Post treatment follow-up of patients: There will be 6 scheduled visits to clinic for monitoring and neurofunctional testing and 5 scheduled telephone contacts to monitor adverse events (AEs) and concomitant medications over the 2 year follow-up period.
End-points: The primary end-point of the trial is safety, measured by numbers of relevant Serious Adverse Events, health screening, neurological assessment and scanning abnormalities. The secondary aim is to evaluate various MRI and other test measures for their potential as efficacy markers for subsequent trials.
Post trial follow up: All trial patients will be flagged by the National Health Service Central Register (NHSCR) Scotland for life-long follow-up. In addition, all patients will be invited to take part in an 8-year follow up trial requiring an annual review by a suitable physician.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CTX0E03 DP | Experimental | Biological: CTX0E03 neural stem cellshuman neural stem cell product, once only injection, increasing doses |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males
- 60 years or over
- Unilateral ischemic stroke involving subcortical white matter or Basal Ganglia 6 months to 5 years before entry
- NIHSS score minimum 6 with hemiparesis (2 or more for motor arm and leg)
- Neurologically stable for 2 m
Key exclusion criteria (10 listed)
- Structural brain vascular lesions requiring surgery or increasing the risk of stereotaxic implantation
- Unstable medical conditions with expected survival <12 months
- Any medical condition that would impair participation (eg progressive neurological disorders, mental illness)
- Major surgery within 30 days
- Previous allogeneic tissue transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CTX0E03 neural stem cellsSingle administration by surgical delivery to the damaged area of the brain | Biological | CTX0E03 DP |
Primary outcome
Incidence of adverse events
Time frame: 1 year
AEs monitored include vital signs, C-reactive protein and full blood count, structural MRI to seek evidence of hemorrhage, new infarction, inflammation or tumor, NIHSS measure (changes greater than 4) to indicate clinically significant neurological deterioration, neurological examination, CTX0E03 antibody screen, changes to concomitant medications
4 secondary outcomes
Barthel Index
Time frame: 1 year
Mini-Mental State Examination
Time frame: 1 year
modified Rankin Score
Time frame: 1 year
EQ-5D
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2023.
- Derived from this study: PubMed 27497862Kalladka D, Sinden J, Pollock K, Haig C, McLean J, Smith W, McConnachie A, Santosh C, Bath PM, Dunn L, Muir KW. Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. Lancet. 2016 Aug 20;388(10046):787-96. doi: 10.1016/S0140-6736(16)30513-X. Epub 2016 Aug 3.
- Derived from this study: PubMed 26752061Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD. Investigation of Content, Stoichiometry and Transfer of miRNA from Human Neural Stem Cell Line Derived Exosomes. PLoS One. 2016 Jan 11;11(1):e0146353. doi: 10.1371/journal.pone.0146353. eCollection 2016.
- Derived from this study: PubMed 25938519Stevanato L, Hicks C, Sinden JD. Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes. J Vis Exp. 2015 Apr 12;(98):52410. doi: 10.3791/52410.
- Derived from this study: PubMed 24725992Stevanato L, Sinden JD. The effects of microRNAs on human neural stem cell differentiation in two- and three-dimensional cultures. Stem Cell Res Ther. 2014 Apr 11;5(2):49. doi: 10.1186/scrt437.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CTX0E03 neural stem cells in people with Stroke, run by ReNeuron Limited at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01151124, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2023.