Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kathleen M. Shannon, Rush University Medical Center
ClinicalTrials.gov Identifier:
NCT01155492
First received: June 15, 2010
Last updated: May 29, 2013
Last verified: May 2013
  Purpose

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.


Condition
Parkinson's Disease
Multiple System Atrophy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Increased Gut Permeability to Lipopolysaccharides (LPS) in Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by Rush University Medical Center:

Primary Outcome Measures:
  • Total urine sugar per 24 hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood endotoxin and cytokine levels

  • Histopathology and immunohistochemistry of colonic mucosa [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    A portion of the colonic tissue will be studied with histopathology and immunohistochemistry techniques for alpha-synuclein pathology, cytokines and inflammatory markers.


Biospecimen Retention:   Samples With DNA

Colonic mucosa biopsies


Enrollment: 43
Study Start Date: September 2007
Study Completion Date: February 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Subjects with Parkinson's disease
Male and female subjects with clinically diagnosed Parkinson's disease, Stage I-IV.
Control subjects
Age- and gender-matched subjects who do not have Parkinson's disease
Multiple system atrophy.
Men and women with clinically diagnosed multiple system atrophy.

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

Ages Eligible for Study:   25 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Subjects with Parkinson's disease Age- and gender-matched controls

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01155492

Locations
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
Rush University Medical Center
Investigators
Principal Investigator: Kathleen M Shannon, M.D. Rush University Medical Center
  More Information

No publications provided by Rush University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kathleen M. Shannon, Professor, Neurological Sciences, Rush University Medical Center
ClinicalTrials.gov Identifier: NCT01155492     History of Changes
Other Study ID Numbers: 07100403
Study First Received: June 15, 2010
Last Updated: May 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Rush University Medical Center:
lipopolysaccharides
etiology
inflammation
colonic bacteria
intestinal permeability

Additional relevant MeSH terms:
Multiple System Atrophy
Parkinson Disease
Shy-Drager Syndrome
Autonomic Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Hypotension
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
Primary Dysautonomias
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014