Clinical trial NCT04956939: Levodopa Response and Gut Microbiome in Patients With Parkinson's Disease
Official title: Levodopa Response and Gut Microbiome in Patients With Parkinson's Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Parkinson Disease
Keywords: levodopa
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2021-07-09
Enrollment: 38
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Fecal microbial community structure and functional changes for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.
timeFrame: During the study visit,1 day
measure: Oral microbial community structure and functional changes for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.
timeFrame: During the study visit,1 day
measure: Change in the measurement of blood biomarker levodopa (ng/mL) over 12 time frames
timeFrame: During the study visit,1 day
measure: Change in the measurement of blood biomarker glucagon-like peptide-1 (GLP-1) (pm) over 12 time frames
timeFrame: During the study visit,1 day
measure: 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.
timeFrame: During the study visit,1 day
measure: Change in the measurement of blood levodopa metabolomics concentrations (ug/mL) across 12 time frames.
timeFrame: During the study visit,1 day
measure: 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
timeFrame: During the study visit,1 day
measure: Change in the measurement of blood targeted trimethylamine N-oxide (TMAO) concentrations (uM) across 12 time frames
timeFrame: During the study visit,1 day
Secondary outcomes:
measure: Food Timing Screener
timeFrame: During the study visit,1 day
measure: Food and Frequency of Consumption
timeFrame: During the study visit,1 day
measure: Single day food recall
timeFrame: During the study visit,1 day
measure: Gastrointestinal Symptom and Severity
timeFrame: During the study visit,1 day
measure: Diet change
timeFrame: During the study visit,1 day
measure: REM Sleep Behavior Disorder assessment
timeFrame: During the study visit,1 day
measure: Sleep Disturbance
timeFrame: During the study visit,1 day
measure: Chronotype
timeFrame: During the study visit,1 day
measure: Functional status in patients with Parkinson's Disease
timeFrame: During the study visit,1 day
measure: Motor speed and lateralized coordination
timeFrame: During the study visit,1 day
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
References: