Effects of Probiotics on Peripheral Immunity in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 88
- 试验地点
- 2
- 主要终点
- Changes in plasma IFN-γ level
研究概览
简要总结
Parkinson's Disease (PD) is a common neurodegenerative disease, with no disease-modifying treatment available, therapy is therefore only symptomatic. The pathophysiology of the disease is still unclear, but inflammatory mechanisms are reported to play a prominent role. An involvement of peripheral adaptive immunity, with an imbalance in T cell subpopulations and in the expression of transcriptional factors (TF) in Cluster of Differentiation (CD) 4 positive T cells has been reported. An initial aggregation of α-synuclein (α-syn) in the gut with subsequent propagation along the vagus nerve to the brain has also been hypothesised. Interestingly, in an α-syn overexpressing murine model, the absence of gut microbiota prevented both microglia activation and motor impairment, pointing to a fundamental role of the microbiota in the development of PD. It has been shown that in Peripheral Blood Mononuclear Cells (PBMC) of PD patients, probiotics modulate the in vitro production of cytokines toward an anti-inflammatory profile. The investigators developed a clinical trial protocol for the evaluation of probiotics' effects on the peripheral immune system profile in Parkinson's Disease patients. ROS, Lymphocyte subpopulations, TF levels in PBMC will be assessed at baseline and after treatment with a mixture of probiotics in PD patients to assess immunomodulatory effects of said treatment. Motor and non-motor symptoms of PD will also be monitored through the trial period.
详细描述
Introduction Parkinson's Disease (PD) is a common neurodegenerative disease, affecting up to 1-2 people in 1000 at any given time. Prevalence increases with age and is estimated at 1% in people over 65.
There is no available treatment to prevent PD onset or to delay its progression and therapy is focused on symptoms management. The administration of carbidopa/levodopa allows for control of motor symptoms, but it becomes less effective as the disease progresses and increasing daily doses causes more frequent and severe side effects.
The histopathologic hallmark of PD is the loss of dopaminergic neurons and accumulation of α-synuclein (α-syn) in surviving neurons, but the underlying pathophysiology is still unclear. Inflammatory mechanisms have been suggested to play a prominent role in the disease, with an imbalance between detrimental and protective immune functions, as well as neurotoxicity caused by reactive oxygen species (ROS).
Further evidence highlights the involvement of peripheral adaptive immunity in PD, reporting an imbalance in T cell subpopulations and in the expression of transcriptional factors in CD4+ T cells in PD patients.
In these patients, non-motor symptoms may precede the onset of a clinically established disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •a diagnosis of Parkinson's Disease;
- •a disease duration between 2 and 5 years at baseline
排除标准
- •past or concomitant autoimmune disease
- •previous or ongoing immune-modulating or immunosuppressive therapy
- •inflammatory bowel diseases, colorectal diseases or past major abdominal or pelvic surgery
- •antibiotics therapy up to three months before enrolment
- •usage of tube feeding
- •known or suspected allergy to any component of the treatment or placebo mixtures
- •known and established cognitive decline or any comorbidity preventing reliable completion of trial assessments
- •motor fluctuations
结局指标
主要结局
Changes in plasma IFN-γ level
时间窗: Baseline, 12 weeks
IFN-γ level will be assessed in plasma samples via ELISA assay.
Changes in plasma IL-4 level
时间窗: Baseline, 12 weeks
IL-4 level will be assessed in plasma samples via ELISA assay.
Changes in ROS production capacity
时间窗: Baseline, 12 weeks
ROS production will be evaluated by the superoxide dismutase-sensitive cytochrome C reduction assay and results of these assays will be expressed as nmol of reduced cytochrome C / 10\^6 cells / 30 min.
Changes in plasma Transforming Growth Factor (TGF)-β level
时间窗: Baseline, 12 weeks
TGF-β level will be assessed in plasma samples via ELISA assay.
Changes in plasma TNF-α level
时间窗: Baseline, 12 weeks
TNF-α level will be assessed in plasma samples via ELISA assay.
Changes in plasma IL-17A level
时间窗: Baseline, 12 weeks
IL-17A level will be assessed in plasma samples via ELISA assay.
Changes in plasma IL-10 level
时间窗: Baseline, 12 weeks
IL-10 level will be assessed in plasma samples via ELISA assay.
次要结局
- Changes in Monocyte subpopulations(Baseline, 12 weeks)
- Changes in CD4+ T cells NR4A2 mRNA levels(Baseline, 12 weeks)
- Changes in Naive-Memory lymphocytes subpopulations(Baseline, 12 weeks)
- Changes in T helper (Th) lymphocytes subpopulations(Baseline, 12 weeks)
- Changes in Regulatory T cells (Treg) lymphocytes subpopulations(Baseline, 12 weeks)
- Changes in CD4+ T cells STAT4 mRNA levels(Baseline, 12 weeks)
- Changes in CD4+ T cells STAT6 mRNA levels(Baseline, 12 weeks)
- Changes in CD4+ T cells RORC mRNA levels(Baseline, 12 weeks)
- Changes in CD4+ T cells GATA3 mRNA levels(Baseline, 12 weeks)
- Changes in CD4+ T cells STAT1 mRNA levels(Baseline, 12 weeks)
- Changes in NK subpopulations(Baseline, 12 weeks)
- Changes in CD4+ T cells TBX21 mRNA levels(Baseline, 12 weeks)
- Changes in CD4+ T cells STAT3 mRNA levels(Baseline, 12 weeks)
- Changes in CD4+ T cells FOXP3 mRNA levels(Baseline, 12 weeks)
研究者
Franca Marino
Professor
Università degli Studi dell'Insubria