Increased Gut Permeability to Lipopolysaccharides (LPS) in Parkinson's Disease

Completed

• Conditions: Parkinson's Disease; Multiple System Atrophy

• Registration Number: NCT01155492
• Lead Sponsor: Rush University Medical Center

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2007-09
• Study First Submitted: 2010-06-15
• Study First Submitted QC: 2010-06-30
• Study First Posted: 2010-07-01
• Primary Completion: 2012-12
• Study Completion: 2013-02
• Status Verified: 2013-05
• Last Update Submitted: 2013-05-29
• Last Update Posted: 2013-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

Not provided

Exclusion Criteria

• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Total urine sugar per 24 hours	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	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	24 hours	Blood endotoxin and cytokine levels
Histopathology and immunohistochemistry of colonic mucosa	24 hours	A portion of the colonic tissue will be studied with histopathology and immunohistochemistry techniques for alpha-synuclein pathology, cytokines and inflammatory markers.

Trial Locations

Locations (1)

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States