Increased Gut Permeability to Lipopolysaccharides (LPS) in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Total urine sugar per 24 hours
研究概览
简要总结
The gut may be a portal of entry for agents that cause or contribute to the causes of Parkinson's disease (PD). The investigators are studying changes in the normal population of gut flora and in intestinal permeability and their associations with early PD.
详细描述
Clinical and pathological data suggest Parkinson's disease (PD) may result from an inflammatory process beginning in the intestinal wall that initiates alpha-synuclein aggregation, which then spreads from neuron to neuron, reaching the central nervous system. Bacteria living within the intestinal tract produce lipopolysaccharide endotoxin, a toxin known to induce parkinsonism in animal models. We hypothesize that exposure to LPS, either from excessive production or excessive absorption may be the cause of this inflammation. This study aims to: (1) describe differences in the population of gut bacteria in PD compared to control subjects; (2) assess leakiness of the gut wall by differential absorption of non-absorbable sugars; (3) measure plasma levels of endotoxin and inflammation; and (4) study characteristic PD pathology and evidence of inflammation in biopsy samples of the colon obtained by sigmoidoscopy.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 25 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Secondary or atypical parkinsonism other than Multiple System Atrophy
- •Occupation or medical treatment known to influence intestinal flora
- •Organic gastrointestinal disease other than hiatal hernia or hemorrhoids; history of gastrointestinal surgery other than remote appendectomy or cholecystectomy.
- •Acute or chronic medical illness that would confound study results.
- •Coagulopathy or use of anticoagulant medications (including aspirin).
- •Chronic use of diuretics
结局指标
主要结局
Total urine sugar per 24 hours
时间窗: 24 hours
Subjects consume a mixture of sugars (lactulose, sucrose), then collect urine for 24 hours. Sugar concentrations in the urine are assayed by gas chromatography.
LH-PCR fingerprint analysis
时间窗: 24 hours
Total genomic DNA will be extracted from colonic mucosa biopsy specimens and lumenal samples, and will be amplified by PCR using bacterial primers. PCR products will be separated and analyzed for amplicon length heterogeneity.
Blood endotoxin and cytokine levels
时间窗: 24 hours
Blood endotoxin and cytokine levels
Histopathology and immunohistochemistry of colonic mucosa
时间窗: 24 hours
A portion of the colonic tissue will be studied with histopathology and immunohistochemistry techniques for alpha-synuclein pathology, cytokines and inflammatory markers.
次要结局
未报告次要终点
研究者
Kathleen M. Shannon
Professor, Neurological Sciences
Rush University Medical Center