The Microbiome in Parkinson's Disease

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

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Diagnostic test: Microbiome specimens in stool

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 Type: Observational
• Enrollment (Actual): 23

Contacts and Locations

• Study Contact: Name: Ashok Sriram; Phone Number: 616-267-7900; Email: ashok.sriram@spectrumhealth.org
• Study Contact Backup: Name: Casey Doyle; Phone Number: 616-486-6128; Email: casey.doyle@spectrumhealth.org

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

We will examine individuals who are current patients of a Spectrum Health Movement Disorder physician with: 1) Tremor-dominant Parkinson's disease, 2) Akinetic-Rigid type Parkinson's disease, 3) Multiple systems atrophy (MSA-P), 4) Levodopa-naïve Parkinson's disease, 5) Tremor-dominant Parkinson's disease with an appendectomy, 6) Akinetic-Rigid Parkinson's disease with an appendectomy, 7) Levodopa-naïve Parkinson's disease with an appendectomy

Description

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.

  3. 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.

    9. 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.

    10. 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 Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tremor-dominant; Tremor-dominant Parkinson's disease	Diagnostic test: Microbiome specimens in stool; Analyzing Microbiome specimens in stool
Akinetic-Rigid; Akinetic-Rigid type Parkinson's disease	Diagnostic test: Microbiome specimens in stool; Analyzing Microbiome specimens in stool
Multiple systems atrophy; Multiple systems atrophy PD	Diagnostic test: Microbiome specimens in stool; Analyzing Microbiome specimens in stool
Levodopa-naïve; Levodopa-naïve Parkinson's disease	Diagnostic test: Microbiome specimens in stool; Analyzing Microbiome specimens in stool
Tremor-dominant / app; Tremor-dominant Parkinson's disease with an appendectomy	Diagnostic test: Microbiome specimens in stool; Analyzing Microbiome specimens in stool
Akinetic-Rigid / app; Akinetic-Rigid Parkinson's disease with an appendectomy	Diagnostic test: Microbiome specimens in stool; Analyzing Microbiome specimens in stool
Levodopa-naïve w/app; Levodopa-naïve Parkinson's disease with an appendectomy	Diagnostic test: Microbiome specimens in stool; Analyzing Microbiome specimens in stool

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The current study determines whether certain Parkinson's subtypes are prone to pro-inflammatory microbiomes.	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).	3 years

Collaborators and Investigators

• Sponsor: Spectrum Health Hospitals
• Collaborators: Van Andel Research Institute
• Investigators: Principal Investigator: Ashok Sriram, MD, MS, Spectrum Health Medical Group

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2017
• Primary Completion (Actual): January 7, 2021
• Study Completion (Actual): January 7, 2021

Study Registration Dates

• First Submitted: April 19, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (Actual): April 26, 2017

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 2016-313

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No