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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04956939
• Other study ID #: RUMC 18032006
• Status: Completed
• Start date: July 17, 2018
• Est. completion date: March 31, 2021

Study information

• Verified date: November 2022
• Source: Rush University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Levodopa (LD) is an effective treatment to control symptoms of Parkinson's disease (PD) and during the first few years of LD treatment patients are said to experience a 'honeymoon' period, reflective of a sustained beneficial response to this dopamine pro-drug. However, the response to LD changes over time and patients require higher and more frequent LD doses. Most patients develop motor response complications such as frequent periods of immobility and involuntary movements. The major unmet need is to preserve the initial, stable, response to LD and prevent the development of motor response complications. It is therefore essential to identify the underlying mechanism for the changes in LD effectiveness.

This study involves only 1 study visit. Prior to the study visit, participants will be asked to complete questionnaires and will receive an at-home stool collection kit. At the time of the study visit, participants will turn in their questionnaires and their at-home stool sample. On the day of the study visit, the patient will have fasted (overnight for 8 hours) and taken their last LD medication 12 hours prior to the visit. Each patient (and healthy control) will bring a home collected stool sample to their scheduled research visit which will be taken and stored in -80 freezers for the microbiota analysis. Oral swab will be collected for oral microbiota analysis. For PD patients only, an indwelling catheter for blood draws will be placed by one of the highly experienced GI infusion nurses and a fasting blood sample will be drawn. At the time of the visit, each patient will be given their morning LD dose (1.5 times their usual dose as they did not take LD for 12 hours), and then both patients and their controls will be given lactulose (20 mg) and have their breath collected every 10 minutes for the first hour, and then every 15 minutes for the following 3 hours (total 4 hours) for measurement of breath hydrogen and methane to assess mouth to cecum transit and presence/absence of small bowel bacteria overgrowth. PD patients will also have a blood sample drawn every 30 minutes, for 4 hours (total 8 draws) to measure LD and LD metabolites in the plasma Patients and controls will be provided a light breakfast (2 white wheat bread toasts with thin layer of butter and coffee). Each patient and control will complete a detailed dietary questionnaire (FFQ and 24 hour diet recall), a food timing questionnaire and screener and a structured demographic questionnaire. PD patients will also complete a questionnaire that includes PD-related information. Patients will also perform a simple finger tapping task to asses and quantify speed of movement before, during and after completion of study. Finger tapping task will be done using 2 mechanical counters mounted on a board. The patients go back and forth between these two counters and the number of taps in 30 seconds will be automatically recorded. In addition, patients will log their motor state (OFF versus ON) every half an hour on a PD diary.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: March 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

FOR PATIENTS WITH PD:

Inclusion Criteria:

• Documented diagnosis of Parkinson's disease

• On Levodopa treatment

Exclusion Criteria:

• 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:

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Low dose levodopa
Low frequency is defined as = 3 LD doses a day
• High dose levodopa
High frequency dosage is defined as = 5 LD doses per day

Locations

Country	Name	City	State
United States	Rush University Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Rush University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Food Timing Screener	Food Timing Screener (FTS) questionnaire. A structured food demographics questionnaire was therefore developed to access food timing. The questionnaire consists of eight questions asking subjects' eating habits on work days and non-work days. Questions include the time of the main meal during work and non-work days, time of last meal before bed, consistency of dinner within work and non-work days, and consistency of breakfast, lunch, and dinner between work and non-work days.	During the study visit,1 day
Secondary	Food and Frequency of Consumption	Food Timing Questionnaires (FTQ) consists of a list of foods and the frequency in which these foods are consumed.	During the study visit,1 day
Secondary	Single day food recall	Automated Self-Administered 24-Hour Recall (ASA24) Dietary Assessment. Total nutrients from all supplements reported in a given day.	During the study visit,1 day
Secondary	Gastrointestinal Symptom and Severity	Patient-Reported Outcomes Measurements Information System (PROMIS) gastrointestinal questionnaire for Belly Pain (6 questions), Bowel Incontinence (4 questions), Constipation (9 questions), and Gas & Bloating (12 questions). Higher score denoted more GI symptoms. Lower score denotes less GI symptoms. Scores range from 20 (low) to 80 (high). A score of 50 is denoted as the general population.	During the study visit,1 day
Secondary	Diet change	Vioscreen Food Frequency Questionnaire (FFQ). Total of 19 measured food components. Vioscreen captures comprehensive dietary behaviors in just 30 minutes. It is a unique dietary questionnaire, management and analysis system that efficiently gathers and manages data that immediately identifies dietary "habits" and counsel for lifestyle changes.	During the study visit,1 day
Secondary	REM Sleep Behavior Disorder assessment	RBD1Q questionnaire that consists of a single question, answered "yes" or "no," as follows: "Have you ever been told, or suspected yourself, that you seem to 'act out your dreams' while asleep (for example, punching, flailing your arms in the air, making running movements, etc.)?"	During the study visit,1 day
Secondary	Sleep Disturbance	The Patient Reported Outcomes Measurement Information System (PROMIS) is a self-reported questionnaire that assess the sleep-wake function in adults.	During the study visit,1 day
Secondary	Chronotype	The Munich ChronoType Questionnaire (MCTQ) uses a self-rated scale to assess individual phase of entrainment on work and work-free days; it is a tool to collect primary sleep times, such as bed- and rise-times, plus the clock time of becoming fully awake as well as sleep latency and inertia, in addition to other time points.	During the study visit,1 day
Secondary	Functional status in patients with Parkinson's Disease	The On-Off Parkinson's Disease Diary by Hauser assesses troublesome and non-troublesome dyskinesia through self-reported time markers.	During the study visit,1 day
Secondary	Motor speed and lateralized coordination	PD patients will take a Finger-Tapping Test (FTT) where hands are laid flat and fingers are lifted one at a time onto two mechanical counters mounted on a board. The patients go back and forth between these two counters and the number of taps in 30 seconds will be recorded.	During the study visit,1 day