Levodopa Response and Gut Microbiome in Patients With Parkinson's Disease

NCT04956939 | Completed

• 1 other identifier: RUMC 18032006
• Study Type: observational
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Levodopa (LD) is an effective treatment to control symptoms of Parkinson's disease (PD). However, the response to (the effectiveness) LD changes over time and patients require higher and more frequent LD doses for treatment. The purpose of this study is to identify what reasons or causes might influence the changes in LD effectiveness, particularly if intestinal bacteria contribute to the breakdown of LD in patients with PD. This study is an observational cohort proof-of-concept study that follows PD patients who take PD at high-frequency doses and low-frequency doses. . Each PD patient will have a household healthy control/spouse enrolled into the study. Single patients with no spouse will still be eligible to enroll.

Conditions

Parkinson Disease

Keywords

levodopa

Outcome Measures

Primary Outcomes (8)

• Fecal microbial community structure and functional changes for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.

  Quantitative polymerase chain reaction (qPCR), 16S rRNA Sequencing and Shotgun Metagenomics

  During the study visit,1 day

• Oral microbial community structure and functional changes for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.

  Quantitative polymerase chain reaction (qPCR), 16S rRNA Sequencing and Shotgun Metagenomics

  During the study visit,1 day

• Change in the measurement of blood biomarker levodopa (ng/mL) over 12 time frames

  ELISA (enzyme-linked immunosorbent assay)

  During the study visit,1 day

• Change in the measurement of blood biomarker glucagon-like peptide-1 (GLP-1) (pm) over 12 time frames

  ELISA (enzyme-linked immunosorbent assay)

  During the study visit,1 day

• Change in the measurment scores of breath hydrogen and methane to assess mouth to cecum transit and presence or absence of small bowel bacteria overgrowth over 16 time frames.

  Lactulose Breath Scoring Test

  During the study visit,1 day

• Change in the measurement of blood levodopa metabolomics concentrations (ug/mL) across 12 time frames.

  Gas Chromatography - Tandem Mass Spectrometry (GC-MS/MS)

  During the study visit,1 day

• Changes in the measurement of blood targeted short chain fatty acids (SCFA) metabolomics concentrations (ug/mL) for acetate, propionate, butyrate and total SCFA across 12-time frames

  Gas Chromatography - Tandem Mass Spectrometry (GC-MS/MS)

  During the study visit,1 day

• Change in the measurement of blood targeted trimethylamine N-oxide (TMAO) concentrations (uM) across 12 time frames

  Liquid Chromatography-Mass Spectrometry (LC-MS/MS)

  During the study visit,1 day

Secondary Outcomes (10)

• Food Timing Screener

  During the study visit,1 day

• Food and Frequency of Consumption

  During the study visit,1 day

• Single day food recall

  During the study visit,1 day

• Gastrointestinal Symptom and Severity

  During the study visit,1 day

• Diet change

  During the study visit,1 day

Study Arms (3)

Group 1

PD patients receiving low frequency dose of levodopa.

Drug: Low dose levodopa

Group 2

PD patients receiving high frequency dose of levodopa.

Drug: High dose levodopa

Control Group

Spouses of PD patients without PD diagnosis

Interventions

Low dose levodopa DRUG

Low frequency is defined as ≤ 3 LD doses a day

Group 1

High dose levodopa DRUG

High frequency dosage is defined as ≥ 5 LD doses per day

Group 2

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We plan to enroll two groups of established PD patients on a stable dose of LD for the prior 4 weeks. We will enroll twelve patients in each of the following two groups: Group 1:"low frequency dose" patients and Group 2:" high frequency dose "patients. Low frequency is defined as ≤ 3 LD doses a day and high frequency as ≥ 5 LD doses per day. Each PD patient will have a household healthy control/spouse enrolled into the study. Single patients with no spouse will still be eligible to enroll.

You may qualify if:

• Documented diagnosis of Parkinson's disease
• On Levodopa treatment

You may not qualify if:

• History of GI diseases \[except for hemorrhoids or occasional (\<3 times a week) heartburn\] like Inflammatory bowel disease or Celiac disease
• Antibiotic use within last 12 weeks
• Use of probiotic supplement over the prior 2 weeks except yogurt
• Intentional change in diet
• Chronic use of NSAIDS. A washout period of 3 weeks is needed before the subject could be enrolled into the study. Low does aspirin is allowed.
• FOR CONTROL GROUP:
• No clinical evidence of neurological disorders including Parkinson's disease
• Live in the same household as the Parkinson's Disease patient or is a first degree relative of the PD patient.
• History of GI diseases \[except for hemorrhoids or occasional (\<3 times a week) heartburn\] like Inflammatory bowel disease or Celiac disease
• Antibiotic use within last 12 weeks
• Use of probiotic supplement over the prior 2 weeks except yogurt
• Intentional change in diet
• Chronic use of NSAIDS. A washout period of 3 weeks is needed before the subject could be enrolled into the study. Low does aspirin is allowed.

Sponsors & Collaborators

• Rush University Medical Center: lead

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Stool collection, saliva and oral swab, breath test, blood samples.

MeSH Terms

Conditions

Parkinson Disease

Interventions

Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Center for Integrated Microbiome and Chronobiology Research

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: July 9, 2021
• Study Start: July 17, 2018
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: November 7, 2022

Record last verified: 2022-11

Locations

US (1)