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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- The safety of xenotransplantation of NTCELL as measured by the incidence of adverse events related to treatment
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
NTCELL
NTCELL Implantation
干预措施: NTCELL Implantation (Biological)
Sham Surgery
Sham Surgery
干预措施: Sham Surgery (Other)
结局指标
主要结局
The safety of xenotransplantation of NTCELL as measured by the incidence of adverse events related to treatment
时间窗: 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
次要结局
- Change in total Unified Parkinson's Disease Rating Scale (UPDRS in the 'off' and 'on' state) over 26 weeks post-intervention compared with baseline(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(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(Baseline and 26 weeks)
- Change in L-dopa dosage over 26 weeks post-intervention compared with baseline(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(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(Baseline and 26 weeks)
- Change in Modified Hoehn and Yahr stage over 26 weeks post-intervention compared with baseline(Baseline and 26 weeks)