Clinical trial NCT01155492: Increased Gut Permeability to Lipopolysaccharides (LPS) in Parkinson's Disease
Official title: Increased Gut Permeability to Lipopolysaccharides (LPS) in Parkinson's Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Parkinson's Disease
Multiple System Atrophy
Keywords: lipopolysaccharides
etiology
inflammation
colonic bacteria
intestinal permeability
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2010-07-01
Enrollment: 43
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with Parkinson's disease Age- and gender-matched controls

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.

Eligibility criteria: 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

Primary outcomes:
measure: Total urine sugar per 24 hours
timeFrame: 24 hours
measure: LH-PCR fingerprint analysis
timeFrame: 24 hours
measure: Blood endotoxin and cytokine levels
timeFrame: 24 hours
measure: Histopathology and immunohistochemistry of colonic mucosa
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
affiliation: Rush University Medical Center
name: Kathleen M Shannon, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One. 2011;6(12):e28032. doi: 10.1371/journal.pone.0028032. Epub 2011 Dec 1.