The Microbiome in Parkinson's Disease

Completed

• Conditions: Parkinson Disease
• Interventions: Diagnostic Test: Microbiome specimens in stool

• Registration Number: NCT03129451
• Lead Sponsor: Spectrum Health Hospitals

Brief Summary

To investigate the dynamic relationship between the intestinal microbiota and Inflammation in subjects with Parkinson's disease.

Detailed Description

To investigate the dynamic relationship between the intestinal microbiota and Inflammation in subjects with Parkinson's disease. The current study examines the differential microbiome of the gut in subjects with parkinsonism. The current study determines whether certain Parkinson's subtypes are prone to pro-inflammatory microbiomes. This study also explores whether the intestinal microbiome in post-appendectomy Parkinson's subjects is modified as appendix has a role in regulating intestinal microbiome. The current study will examine whether microbiome changes influence inflammatory markers in the blood.

Study Timeline

• Study Start: 2017-04-17
• Study First Submitted: 2017-04-19
• Study First Submitted QC: 2017-04-21
• Study First Posted: 2017-04-26
• Primary Completion: 2021-01-07
• Study Completion: 2021-01-07
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-05
• Last Update Posted: 2024-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• Individuals with Parkinson's disease (including multiple system atrophy). Males and females are eligible for the study. Appendectomized cohort must have had their appendectomy at least 20 years before Parkinson's disease onset

Exclusion Criteria

• 1. Body Mass Index greater than or equal to 35 or less than or equal to 18. 2. Vital signs outside of acceptable range at Screening Visit, i.e., blood pressure >160/100, oral temperature >100°F, pulse >100.

  2. Use of any of the following drugs within the last 6 months:

  • systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral);

  • cytokines;

  • methotrexate or immunosuppressive cytotoxic agents;

  • large doses of commercial probiotics consumed (greater than or equal to 108 cfu or organisms per day) - includes tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component. Ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply.

    4. Acute viral/bacterial infection disease at the time of sampling (defer sampling until subject recovers). Acute disease is defined as the presence of a moderate or severe illness with or without fever.

    5. Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet.

    6. Recent history of chronic alcohol consumption defined as more than five 1.5- ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or five 5-ounce servings of wine per day.

    7. Positive test for HIV, HBV or HCV. 8. Any confirmed or suspected condition/state of immunosuppression or immunodeficiency (primary or acquired) including HIV infection.

    8. Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time.

    9. History of active uncontrolled gastrointestinal disorders or diseases including:

  • inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis;

  • irritable bowel syndrome (IBS) (moderate-severe);

  • persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated); 11. Female who is pregnant or lactating. 12. Atypical or secondary Parkinson's disease 13. Adults that are unable to consent, individuals that are not yet adults and prisoners are not eligible for this study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Levodopa-naïve	Microbiome specimens in stool	Levodopa-naïve Parkinson's disease
Akinetic-Rigid	Microbiome specimens in stool	Akinetic-Rigid type Parkinson's disease
Tremor-dominant	Microbiome specimens in stool	Tremor-dominant Parkinson's disease
Akinetic-Rigid / app	Microbiome specimens in stool	Akinetic-Rigid Parkinson's disease with an appendectomy
Multiple systems atrophy	Microbiome specimens in stool	Multiple systems atrophy PD
Levodopa-naïve w/app	Microbiome specimens in stool	Levodopa-naïve Parkinson's disease with an appendectomy
Tremor-dominant / app	Microbiome specimens in stool	Tremor-dominant Parkinson's disease with an appendectomy

Primary Outcome Measures

Name	Time	Method
The current study determines whether certain Parkinson's subtypes are prone to pro-inflammatory microbiomes.	3 years	Differences in microbiome abundance will be detected using a Kruskal-Wallis' test generating a Benjamini-Hochberg false discovery rate (FDR)-corrected P value (\<0.05 for significance). For the microbiome analysis, in silico community functional predictions will be performed using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) and significant differences in Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog (KO) abundances between groups will be identified (FDR-corrected P value \<0.05 for significance). Putative "proinflammatory" and "anti-inflammatory" bacteria taxa will be classified based on previous reports (and the references therein) (see Keshavarzian et al., 2015). Differences in inflammatory metabolite abundance will be detected using a Kruskal-Wallis' test generating a Benjamini-Hochberg false discovery rate (FDR)-corrected P value (0.05).

Trial Locations

Locations (1)

Spectrum Health; 🇺🇸 Grand Rapids, Michigan, United States