Parkinson's DiseasePhase 2NCT02683629
Investigation of the Safety and Efficacy of NTCELL® [Immunoprotected (Alginate-Encapsulated) Porcine Choroid Plexus Cells for Xenotransplantation] in Patients With Parkinson's Disease
A Phase 2 study testing NTCELL Implantation in people with Parkinson's Disease, run by Living Cell Technologies at 1 site in New Zealand.
Trial summary
To assess the safety of xenotransplantation of NTCELL [immunoprotected (alginate-encapsulated) choroid plexus cells] in patients with Parkinson's disease, assessed over the duration of the study, by monitoring the occurrence of adverse events and serious adverse events, including clinical and laboratory evidence of… Read more about this study
- Who is it for?
- Ages 40 to 65 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- NTCELL Implantation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteNew Zealand
- Study dates
- Feb 2016to 2 May 2019
- Phase
- Phase 2
- 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 40 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (males or females) in the age range 40 to 65 years
- Diagnosis of Parkinson's disease (minimum duration of 5 years) in accordance with the London Brain Bank criteria
- Patients diagnosed with idiopathic Parkinson's disease
- Optimum medication for Parkinson's disease
- Expected to meet the criteria for DBS in the future, in the opinion of the Investigator
- If female, no childbearing capability (those who are more than 2 years post-menopausal or have undergone voluntary sterilisation can be considered for enrolment)
- Provision of written informed consent. Patients will be required to agree to comply with all tests and visits specified in the protocol, and they (and their partners/close contacts) will also be required to consent to long-term microbiological monitoring, which is an integral part of the study
Who cannot join
- Any history of central nervous system infection
- Significant dementia as determined by neuropsychiatric assessment
- Focal neurological defects
- Evidence of significant ongoing medical or psychiatric disorders
- Secondary parkinsonism
- Severe autonomic symptoms
Show all 29Show fewer
- Atypical Parkinson's disease
- History of substance abuse
- Body mass index (BMI) ≥ 30 kg/m2 or ≤ 20 kg/m2
- Serious comorbid conditions that, in the opinion of the Investigator, are likely to affect participation in the study, including:
- Previous coronary heart disease manifesting as non-ST elevation myocardial infarction (NSTEMI), Q-wave infarction or unstable angina; coronary artery bypass graft (CABG); or percutaneous angioplasty
- Previous cerebrovascular disease manifesting as transient ischaemic attacks (TIAs) or stroke
- Peripheral vascular disease with foot ulcer and/or previous amputation
- History of New York Heart Association (NYHA) class II, III or IV congestive heart failure (CHF) and/or chronic atrial fibrillation
- Chronic obstructive pulmonary disease (COPD) or asthma with previous hospitalisation for decompensation; a requirement for mechanical ventilation at any stage; or long-term treatment with oral corticosteroids
- Liver disease with abnormal liver function tests defined as serum bilirubin ≥ 20 µmol/L, and/or ALT ≥ 100 U/L, and/or GGT ≥ 100 U/L, and/or albumin < 35 g/L
- Haematological disorders, including haemoglobin ≤ 110 g/L or platelet count < 80 x 109/L
- Kidney disease, defined as serum creatinine > 130 μmol/L in men and > 110 μmol/L in women and/or haematuria and/or active urinary sediment or casts
- Peptic ulcer disease and/or history of previous gastrointestinal bleeding
- Malignancy other than basal cell carcinoma
- History of epilepsy
- Untreated hypothyroidism
- Known adrenal insufficiency
- Previous brain surgery for Parkinson's disease
- Poor candidate for any surgery
- HIV antibody and/or risk factors for HIV infection
- Positive hepatitis C antibody, positive hepatitis B surface antigen, and hepatitis B core antibody
- Current administration of immunosuppressive medications (e.g. cyclosporin, tacrolimus, sirolimus, mycophenolate mofetil, muromonab-CD3, daclizumab, basiliximab, antithymocyte globulin, interferons) for other disease conditions
- Any other condition that, in the opinion of the Investigator, may interfere with adherence to the study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIb, Randomised, Double-blind, Placebo-controlled, Dose-range Investigation of the Safety and Efficacy of NTCELL® [Immunoprotected (Alginate-Encapsulated) Porcine Choroid Plexus Cells for Xenotransplantation] in Patients With Parkinson's Disease
To assess the safety of xenotransplantation of NTCELL [immunoprotected (alginate-encapsulated) choroid plexus cells] in patients with Parkinson's disease, assessed over the duration of the study, by monitoring the occurrence of adverse events and serious adverse events, including clinical and laboratory evidence of xenogeneic infection in transplant recipients and their partners/close contacts. Subsequent safety follow-up will include lifelong monitoring for clinical and laboratory evidence of xenogeneic infection.
To assess the efficacy of xenotransplantation of NTCELL [immunoprotected (alginate-encapsulated) choroid plexus cells] in patients with Parkinson's disease. This will be quantified by testing the secondary endpoints of the trial as described below (see Endpoints/Outcome Measures).
Read the detailed description
Parkinson's disease is characterized by widespread neural degeneration, particularly in the substantia nigra and its projections to the basal ganglia. Current therapy for Parkinson's disease is purely symptomatic. There is a pressing need for a treatment that reverses or slows the degeneration of the nigrostriatal pathway.
Numerous transplant-based therapies have attempted to support, repair or replace the degenerating nigrostriatal neurons. These have included the transplantation of foetal and other neuronal stem cells, gene transfers, and the implantation of devices releasing neural growth factors. All these have been shown to have some effectiveness in animal models, but have been generally disappointing in human studies.
Intracranial choroid plexus cell transplantation has the potential to deliver biological neural agents for the treatment of Parkinson's disease which cannot be achieved by conventional treatment. The overall aim of delivering neural proteins and compounds over many months to the basal ganglia of the brain is to enhance neural repair currently not possible with antiparkinsonian medication or deep brain stimulation (DBS).
As animal-derived tissues have to be protected from immune rejection when transplanted into humans, transplants are usually accompanied by immunosuppressive therapy. However, porcine choroid plexus cells are preferably implanted without the use of immunosuppressive drugs which cause significant morbidity. To protect them from immune rejection, the cells can be encapsulated in alginate microcapsules which permit the inward passage of nutrients and the outward passage of biologic neural proteins and compounds normally secreted by choroid plexus cells. Alginate-encapsulated porcine choroid plexus cells implanted into the brain without immunosuppressive drugs have survived rejection for many months in animal studies.
NTCELL comprises neonatal porcine choroid plexus cells encapsulated in alginate microcapsules.
The bilateral dose that will be administered to the 18 patients (initially 3 groups of 6 patients, randomised 4:2 NTCELL:sham surgery) enrolled in this trial will be up to a total of twice the human equivalent dose administered unilaterally in LCT's non-human primate study. Thus up to 240 NTCELL microcapsules (± 5%) administered on each side of the brain.
If there are no significant safety issues after implantation of the first group of patients, the second group of patients will then be scheduled to receive implants of NTCELL.
If there are no significant safety issues after implantation of the second group of patients, the third group of patients will then be scheduled to receive implants of NTCELL.
This study will adopt an adaptive design in respect to the choice of dose of NTCELL for the fourth group of patients (those patients who originally received sham surgery in Groups 1-3). Following unblinding of the study after Groups 1-3 have reached 26-week follow-up, an interim analysis, for safety and efficacy, will be undertaken.
If there are no significant safety issues, the last group of patients, Group 4, (who originally received sham surgery) will be scheduled to receive NTCELL implants. The dose of NTCELL given will be determined by the DSMB following a proposal from the Principal Investigator, based on the results of the interim analysis.
Parkinson's disease patients will be followed up for 26 weeks after receiving either an implantation of NTCELL or sham surgery.
- Conditions
- Parkinson's Disease
- Being tested
- NTCELL Implantation, Sham Surgery
- Keywords
- Parkinson's Disease, Xenotransplantation, choroid plexus
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NTCELL ImplantationBiological
NTCELL Implantation
Sham SurgeryOther
Sham Surgery
| Study group | Role | What they receive |
|---|---|---|
| NTCELL | Experimental | NTCELL Implantation Receives: Biological: NTCELL Implantation |
| Sham Surgery | Sham comparator | Sham Surgery Receives: Other: Sham Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of xenotransplantation of NTCELL as measured by the incidence of adverse events related to treatment
Adverse events can result from, for example, abnormal clinical laboratory tests (including xenogeneic viral analysis), abnormal physical examination findings, any abnormal findings following review by an infectious disease physician. These multiple assessments result in the one outcome measure which is the incidence of treatment emergent adverse events
Measured: up to 26 weeks
Secondary outcomes (7)
Change in total Unified Parkinson's Disease Rating Scale (UPDRS in the 'off' and 'on' state) over 26 weeks post-intervention compared with baseline
Measured: Baseline and 26 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III in the 'on' state) over 26 weeks post-intervention compared with baseline
Measured: Baseline and 26 weeks
Change in Quality of life as assessed by Parkinson's Disease Questionnaire (PDQ-39) over 26 weeks post-intervention compared with baseline
Measured: Baseline and 26 weeks
Change in L-dopa dosage over 26 weeks post-intervention compared with baseline
Measured: Baseline and 26 weeks
Change in scores measured by the Unified Dyskinesia Rating Scale (UDysRS Parts I, II, III, IV - Parts III and IV will be performed in the 'off' and 'on' state) over 26 weeks post-intervention compared with baseline
Measured: Baseline and 26 weeks
Change in scores measured by the modified walking test in accordance with the CAPSIT-PD protocol (Defer et al. 1999) over 26 weeks post-intervention compared with baseline
Measured: Baseline and 26 weeks
Change in Modified Hoehn and Yahr stage over 26 weeks post-intervention compared with baseline
Measured: Baseline and 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2016 (estimated)
- Study startFeb 2016
- Primary completionOct 2017
- Study completion2 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Living Cell Technologies
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Statistecol Consultants Limited
- Responsible party
- Sponsor
- Investigators
- Barry Snow, Principal investigator, Auckland City Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02683629
- Sponsor's protocol ID
- LCT/PD-015
- Status last verified
- May 2019
- First submitted
- 8 Feb 2016
- Last updated
- 14 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: International conference presentations, press releases, International journal publications
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Randomised, Double-blind, Placebo-controlled, Dose-range Investigation of the Safety and Efficacy of NTCELL® [Immunoprotected (Alginate-Encapsulated) Porcine Choroid Plexus Cells for Xenotransplantation] in Patients With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT02683629
- Acronym / sponsor ID
- LCT/PD-015
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's Disease, Xenotransplantation, choroid plexus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Living Cell TechnologiesIndustry (pharma, biotech, devices)
- Collaborators
- Statistecol Consultants Limited
- Study start
- Feb 2016 (actual)
- Primary completion
- Oct 2017 (actual)
- Study completion
- 2 May 2019 (actual)
- First posted
- 17 Feb 2016 (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.
To assess the safety of xenotransplantation of NTCELL [immunoprotected (alginate-encapsulated) choroid plexus cells] in patients with Parkinson's disease, assessed over the duration of the study, by monitoring the occurrence of adverse events and serious adverse events, including clinical and laboratory evidence of xenogeneic infection in transplant recipients and their partners/close contacts. Subsequent safety follow-up will include lifelong monitoring for clinical and laboratory evidence of xenogeneic infection.
To assess the efficacy of xenotransplantation of NTCELL [immunoprotected (alginate-encapsulated) choroid plexus cells] in patients with Parkinson's disease. This will be quantified by testing the secondary endpoints of the trial as described below (see Endpoints/Outcome Measures).
Detailed description
Parkinson's disease is characterized by widespread neural degeneration, particularly in the substantia nigra and its projections to the basal ganglia. Current therapy for Parkinson's disease is purely symptomatic. There is a pressing need for a treatment that reverses or slows the degeneration of the nigrostriatal pathway.
Numerous transplant-based therapies have attempted to support, repair or replace the degenerating nigrostriatal neurons. These have included the transplantation of foetal and other neuronal stem cells, gene transfers, and the implantation of devices releasing neural growth factors. All these have been shown to have some effectiveness in animal models, but have been generally disappointing in human studies.
Intracranial choroid plexus cell transplantation has the potential to deliver biological neural agents for the treatment of Parkinson's disease which cannot be achieved by conventional treatment. The overall aim of delivering neural proteins and compounds over many months to the basal ganglia of the brain is to enhance neural repair currently not possible with antiparkinsonian medication or deep brain stimulation (DBS).
As animal-derived tissues have to be protected from immune rejection when transplanted into humans, transplants are usually accompanied by immunosuppressive therapy. However, porcine choroid plexus cells are preferably implanted without the use of immunosuppressive drugs which cause significant morbidity. To protect them from immune rejection, the cells can be encapsulated in alginate microcapsules which permit the inward passage of nutrients and the outward passage of biologic neural proteins and compounds normally secreted by choroid plexus cells. Alginate-encapsulated porcine choroid plexus cells implanted into the brain without immunosuppressive drugs have survived rejection for many months in animal studies.
NTCELL comprises neonatal porcine choroid plexus cells encapsulated in alginate microcapsules.
The bilateral dose that will be administered to the 18 patients (initially 3 groups of 6 patients, randomised 4:2 NTCELL:sham surgery) enrolled in this trial will be up to a total of twice the human equivalent dose administered unilaterally in LCT's non-human primate study. Thus up to 240 NTCELL microcapsules (± 5%) administered on each side of the brain.
If there are no significant safety issues after implantation of the first group of patients, the second group of patients will then be scheduled to receive implants of NTCELL.
If there are no significant safety issues after implantation of the second group of patients, the third group of patients will then be scheduled to receive implants of NTCELL.
This study will adopt an adaptive design in respect to the choice of dose of NTCELL for the fourth group of patients (those patients who originally received sham surgery in Groups 1-3). Following unblinding of the study after Groups 1-3 have reached 26-week follow-up, an interim analysis, for safety and efficacy, will be undertaken.
If there are no significant safety issues, the last group of patients, Group 4, (who originally received sham surgery) will be scheduled to receive NTCELL implants. The dose of NTCELL given will be determined by the DSMB following a proposal from the Principal Investigator, based on the results of the interim analysis.
Parkinson's disease patients will be followed up for 26 weeks after receiving either an implantation of NTCELL or sham surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NTCELL | Experimental | Biological: NTCELL ImplantationNTCELL Implantation |
| Sham Surgery | Sham comparator | Other: Sham SurgerySham Surgery |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adults (males or females) in the age range 40 to 65 years
- Diagnosis of Parkinson's disease (minimum duration of 5 years) in accordance with the London Brain Bank criteria
- Patients diagnosed with idiopathic Parkinson's disease
- Optimum medication for Parkinson's disease
- Expected to meet the criteria for DBS in the future, in the opinion of the Investigator
Key exclusion criteria (29 listed)
- Any history of central nervous system infection
- Significant dementia as determined by neuropsychiatric assessment
- Focal neurological defects
- Evidence of significant ongoing medical or psychiatric disorders
- Secondary parkinsonism
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 |
|---|---|---|
| NTCELL ImplantationNTCELL Implantation | Biological | NTCELL |
| Sham SurgerySham Surgery | Other | Sham Surgery |
Primary outcome
The safety of xenotransplantation of NTCELL as measured by the incidence of adverse events related to treatment
Time frame: up to 26 weeks
Adverse events can result from, for example, abnormal clinical laboratory tests (including xenogeneic viral analysis), abnormal physical examination findings, any abnormal findings following review by an infectious disease physician. These multiple assessments result in the one outcome measure which is the incidence of treatment emergent adverse events
7 secondary outcomes
Change in total Unified Parkinson's Disease Rating Scale (UPDRS in the 'off' and 'on' state) over 26 weeks post-intervention compared with baseline
Time frame: Baseline and 26 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III in the 'on' state) over 26 weeks post-intervention compared with baseline
Time frame: Baseline and 26 weeks
Change in Quality of life as assessed by Parkinson's Disease Questionnaire (PDQ-39) over 26 weeks post-intervention compared with baseline
Time frame: Baseline and 26 weeks
Change in L-dopa dosage over 26 weeks post-intervention compared with baseline
Time frame: Baseline and 26 weeks
Change in scores measured by the Unified Dyskinesia Rating Scale (UDysRS Parts I, II, III, IV - Parts III and IV will be performed in the 'off' and 'on' state) over 26 weeks post-intervention compared with baseline
Time frame: Baseline and 26 weeks
Change in scores measured by the modified walking test in accordance with the CAPSIT-PD protocol (Defer et al. 1999) over 26 weeks post-intervention compared with baseline
Time frame: Baseline and 26 weeks
Change in Modified Hoehn and Yahr stage over 26 weeks post-intervention compared with baseline
Time frame: Baseline and 26 weeks
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 14 May 2019.
- Individual participant dataSharing planned: Yes. International conference presentations, press releases, International journal publications
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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.
Barry Snow principal investigator
Auckland City Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NTCELL Implantation in people with Parkinson's Disease, run by Living Cell Technologies at 1 site in New Zealand.
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 7 inclusion and 29 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 14 May 2019. 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 New Zealand. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The safety of xenotransplantation of NTCELL as measured by the incidence of adverse events related to treatment (time frame: up to 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 May 2019.