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

Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01155492
• Other study ID #: 07100403
• Status: Completed
• Phase: N/A
• First received: June 15, 2010
• Last updated: May 29, 2013
• Start date: September 2007
• Est. completion date: February 2013

Study information

• Verified date: May 2013
• Source: Rush University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: February 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 25 Years and older

Eligibility

Inclusion Criteria--Parkinson's disease:

• Clinically diagnosed Parkinson's disease

• Hoehn & Yahr stage 1-2.5

• No symptomatic treatment of Parkinson's disease symptoms

Inclusion Criteria--Multiple System Atrophy

• Clinically diagnosed Multiple System Atrophy.

Inclusion Criteria--Control subjects:

• No diagnosis of Parkinson's disease and no signs of Parkinson's disease on screening neurological examination

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

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Multiple System Atrophy
• Parkinson Disease
• Parkinson's Disease
• Shy-Drager Syndrome

Locations

Country	Name	City	State
United States	Rush University Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Rush University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total urine sugar per 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.	24 hours	No
Primary	LH-PCR fingerprint analysis	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.	24 hours	No
Primary	Blood endotoxin and cytokine levels	Blood endotoxin and cytokine levels	24 hours	No
Primary	Histopathology and immunohistochemistry of colonic mucosa	A portion of the colonic tissue will be studied with histopathology and immunohistochemistry techniques for alpha-synuclein pathology, cytokines and inflammatory markers.	24 hours	No