Levodopa Response and Gut Microbiome in Patients With Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Observational

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.
    

Intervention name(s): Low dose levodopa; High dose levodopa
Intervention type(s): Drug; Drug
Intervention description(s): Low frequency is defined as ≤ 3 LD doses a day; High frequency dosage is defined as ≥ 5 LD doses per day
Intervention MeSH terms: Levodopa
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.
      
Biospecimen description: 
      Stool collection, saliva and oral swab, breath test, blood samples.
    
Keywords: levodopa