Parkinson DiseaseNCT04956939
Levodopa Response and Gut Microbiome in Patients With Parkinson's Disease
An observational study of Parkinson Disease, run by Rush University Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Low dose levodopa and High dose levodopa
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2018to 31 Mar 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- Documented diagnosis of Parkinson's disease
- On Levodopa treatment
- 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.
Who cannot join
- 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:
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rush University Medical Center
Chicago, Illinois, 60612
About this study
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.
Read the 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.
- Conditions
- Parkinson Disease
- Being tested
- Low dose levodopa, High dose levodopa
- Keywords
- levodopa
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low dose levodopaDrug
Low frequency is defined as ≤ 3 LD doses a day
High dose levodopaDrug
High frequency dosage is defined as ≥ 5 LD doses per day
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | PD patients receiving low frequency dose of levodopa. Receives: Drug: Low dose levodopa | |
| Group 2 | PD patients receiving high frequency dose of levodopa. Receives: Drug: High dose levodopa | |
| Control Group | Spouses of PD patients without PD diagnosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: During the study visit,1 day
Secondary outcomes (10)
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.
Measured: During the study visit,1 day
Food and Frequency of Consumption
Food Timing Questionnaires (FTQ) consists of a list of foods and the frequency in which these foods are consumed.
Measured: During the study visit,1 day
Single day food recall
Automated Self-Administered 24-Hour Recall (ASA24) Dietary Assessment. Total nutrients from all supplements reported in a given day.
Measured: During the study visit,1 day
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.
Measured: During the study visit,1 day
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.
Measured: During the study visit,1 day
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.)?"
Measured: During the study visit,1 day
Sleep Disturbance
The Patient Reported Outcomes Measurement Information System (PROMIS) is a self-reported questionnaire that assess the sleep-wake function in adults.
Measured: During the study visit,1 day
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.
Measured: During the study visit,1 day
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.
Measured: During the study visit,1 day
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.
Measured: During the study visit,1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2021
- Study start17 Jul 2018
- Primary completion31 Mar 2021
- Study completion31 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Rush University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ali Keshavarzian, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04956939
- Sponsor's protocol ID
- RUMC 18032006
- Status last verified
- Nov 2022
- First submitted
- 11 Jun 2021
- Last updated
- 7 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levodopa Response and Gut Microbiome in Patients With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT04956939
- Acronym / sponsor ID
- RUMC 18032006
- Conditions
- Parkinson Disease
- Keywords
- levodopa
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Study start
- 17 Jul 2018 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 9 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | Drug: Low dose levodopaPD patients receiving low frequency dose of levodopa. |
| Group 2 | – | Drug: High dose levodopaPD patients receiving high frequency dose of levodopa. |
| Control Group | – | –Spouses of PD patients without PD diagnosis |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- Documented diagnosis of Parkinson's disease
- On Levodopa treatment
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low dose levodopaLow frequency is defined as ≤ 3 LD doses a day | Drug | Group 1 |
| High dose levodopaHigh frequency dosage is defined as ≥ 5 LD doses per day | Drug | Group 2 |
Primary outcome
Fecal microbial community structure and functional changes for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.
Time frame: During the study visit,1 day
Quantitative polymerase chain reaction (qPCR), 16S rRNA Sequencing and Shotgun Metagenomics
Oral microbial community structure and functional changes for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.
Time frame: During the study visit,1 day
Quantitative polymerase chain reaction (qPCR), 16S rRNA Sequencing and Shotgun Metagenomics
Change in the measurement of blood biomarker levodopa (ng/mL) over 12 time frames
Time frame: During the study visit,1 day
ELISA (enzyme-linked immunosorbent assay)
Change in the measurement of blood biomarker glucagon-like peptide-1 (GLP-1) (pm) over 12 time frames
Time frame: During the study visit,1 day
ELISA (enzyme-linked immunosorbent assay)
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.
Time frame: During the study visit,1 day
Lactulose Breath Scoring Test
Change in the measurement of blood levodopa metabolomics concentrations (ug/mL) across 12 time frames.
Time frame: During the study visit,1 day
Gas Chromatography - Tandem Mass Spectrometry (GC-MS/MS)
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
Time frame: During the study visit,1 day
Gas Chromatography - Tandem Mass Spectrometry (GC-MS/MS)
Change in the measurement of blood targeted trimethylamine N-oxide (TMAO) concentrations (uM) across 12 time frames
Time frame: During the study visit,1 day
Liquid Chromatography-Mass Spectrometry (LC-MS/MS)
10 secondary outcomes
Food Timing Screener
Time frame: During the study visit,1 day
Food and Frequency of Consumption
Time frame: During the study visit,1 day
Single day food recall
Time frame: During the study visit,1 day
Gastrointestinal Symptom and Severity
Time frame: During the study visit,1 day
Diet change
Time frame: During the study visit,1 day
REM Sleep Behavior Disorder assessment
Time frame: During the study visit,1 day
Sleep Disturbance
Time frame: During the study visit,1 day
Chronotype
Time frame: During the study visit,1 day
Functional status in patients with Parkinson's Disease
Time frame: During the study visit,1 day
Motor speed and lateralized coordination
Time frame: During the study visit,1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson Disease, run by Rush University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fecal microbial community structure and functional changes for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea. (time frame: During the study visit,1 day). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2022.