Parkinson's Disease, Small Intestinal Bacterial Overgrowth
Conditions
Brief summary
This study investigates the effect of treating Small Intestinal Bacterial Overgrowth (SIBO) in patients with Parkinson's Disease (PD). It will test the hypothesis that treating SIBO with the antibiotic rifaximin will improve motor complications in previously SIBO-positive PD patients.
Detailed description
Parkinson's Disease (PD) patients with motor fluctuations will be screened for the presence of Small Intestinal Bacterial Overgrowth (SIBO) using two hydrogen breath tests. SIBO-positive individuals will be eligible to enroll, and randomized to receive either rifaximin or placebo. This study includes two treatment regimens (including a placebo control), designed so that all patients will receive the active drug at some point during the trial. Motor outcomes will be followed for 3 or 6 months following enrollment, depending on the treatment arm to which the subject has been assigned. The primary endpoint is to assess the effect of rifaximin treatment to decrease off time in SIBO-positive PD patients. This pilot study will support the design of a larger, randomized controlled trial investigating the effect of SIBO eradication on reducing motor complications in PD patients with motor fluctuations. The current proposal is designed to demonstrate our ability to detect and treat SIBO in PD patients with motor fluctuations, to inform selection of the best SIBO detection method, to determine the optimal timeline for assessing motor endpoints, and to estimate the duration of benefits after treatment.
Interventions
DRUGRifaximin
Rifaximin is an antibiotic used to treat SIBO. It is a 7-day course of treatment followed by three or six months of follow-up. This is a placebo-controlled study designed so that all participants will receive the active drug at least once during the study.
DRUGPlacebo
Placebo matching Rifaximin treatment.
Sponsors
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Participants randomized to the drug ended their study participation at 3 months without switching over to a placebo. Those randomized to placebo were switched to the drug after 3 months and followed for another 3 months (6 months total).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of idiopathic PD * Daily off time ≥ 4 hours * No changes in levodopa or any other dopaminergic medications expected during the course of the study * Will be screened for cognitive ability (Montreal Cognitive Assessment score of ≥ 24) prior to enrollment * Will be screened for presence of SIBO prior to enrollment
Exclusion criteria
* Any comorbid non-PD-associated gastrointestinal (e.g., achlorhydria) or systemic diseases that may alter absorption or confound the study results * Exposure to proton pump inhibitors, immunosuppressive drugs, medications that affect GI motility (such as prokinetics, anticholinergics, and tricyclic antidepressants), antibiotics or any other drugs that affect the intestinal flora (such as laxatives) within a month prior to enrollment. * Prior deep brain stimulation or ablative functional neurosurgery. * Prior allergy to rifaximin * Women who are pregnant, lactating, or plan to become pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Off Time as Measured by Patient Diary | baseline to 1 month and 3 months; new baseline at 3 months to 4 months and 6 months | OFF time is the time in which levodopa has ceased to be effective and Parkinsonian symptoms reemerge. |
| Change in Off Time as Measured by Wireless Computer Monitoring System | 1, 3, and 6 months | This outcome measure was not analyzed due to low subject enrollment as well as poor subject compliance or data quality in some cases. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rifaximin (3-month Follow-up) Participants in this group received a 7-day treatment with Rifaximin and were followed for three months. Participants were blinded to their treatment assignment until the conclusions of the 3-month visit. | 2 |
| Placebo Then Rifaximin (6-month Follow-up) Participants in this group received a 7-day treatment with placebo and were followed for three months. Participants were blinded to their treatment assignment until the conclusions of the 3-month visit. At the end of the 3-month visit, they were given a 7-day course of Rifaximin and followed for an additional 3 months. | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Rifaximin (3-month Follow-up) | Placebo Then Rifaximin (6-month Follow-up) | Total |
|---|---|---|---|
| Age, Continuous | 72.2 years STANDARD_DEVIATION 5.3 | 61.2 years STANDARD_DEVIATION 5.8 | 66.7 years STANDARD_DEVIATION 7.8 |
| OFF time | 1.4 hours STANDARD_DEVIATION 2 | 5.2 hours STANDARD_DEVIATION 0.7 | 3.3 hours STANDARD_DEVIATION 2.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 2 |
| other Total, other adverse events | 0 / 4 | 0 / 2 |
| serious Total, serious adverse events | 0 / 4 | 0 / 2 |
Outcome results
Primary
Change in Off Time as Measured by Patient Diary
OFF time is the time in which levodopa has ceased to be effective and Parkinsonian symptoms reemerge.
Time frame: baseline to 1 month and 3 months; new baseline at 3 months to 4 months and 6 months
Population: Participants in this group completed the study at 3 months after treatment with rifaximin. They were not assessed at 4 and 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rifaximin (3-month Follow-up) | Change in Off Time as Measured by Patient Diary | 1 month change from baseline | -1.4 hours | Standard Deviation 2 |
| Rifaximin (3-month Follow-up) | Change in Off Time as Measured by Patient Diary | 3 month change from baseline | -0.9 hours | Standard Deviation 1.3 |
| Placebo Then Rifaximin | Change in Off Time as Measured by Patient Diary | 1 month change from baseline | -2.8 hours | Standard Deviation 0.7 |
| Placebo Then Rifaximin | Change in Off Time as Measured by Patient Diary | 3 month change from baseline | -2.0 hours | Standard Deviation 2.8 |
| Placebo Then Rifaximin | Change in Off Time as Measured by Patient Diary | 4 month change from new baseline (P to R group only) | -1.4 hours | Standard Deviation 2.5 |
| Placebo Then Rifaximin | Change in Off Time as Measured by Patient Diary | 6 month change from new baseline (P to R group only) | -2.2 hours | Standard Deviation 3.5 |
Primary
Change in Off Time as Measured by Wireless Computer Monitoring System
This outcome measure was not analyzed due to low subject enrollment as well as poor subject compliance or data quality in some cases.
Time frame: 1, 3, and 6 months
Population: This outcome measure was not analyzed due to low subject enrollment as well as poor subject compliance or data quality in some cases. No data were collected for this outcome measure.