Parkinson Disease
Conditions
Keywords
short chain fatty acid, butyrate, tributyrin, functional neuroimaging
Brief summary
Small exploratory open-label pilot study to assess the short-chain fatty acid (SCFA) prodrug tributyrin as a potential therapy for persons with Parkinson disease
Detailed description
The overarching goal of this small exploratory open-label pilot study is to explore metabolic (glucose metabolism, butyrate) and cognition (MoCa) before and after open-label treatment with the short-chain fatty acid (SCFA) prodrug tributyrin in a small pilot study in PD and normal control older adults. Positive findings in this small exploratory pilot trial may support target engagement study of SCFA supplementation in normal adults and PD.
Interventions
DRUGtributyrin
Post-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.
Sponsors
Nicolaas Bohnen, MD, PhD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy control volunteers over 45 years of age * People with Parkinson Disease over 45 years of age
Exclusion criteria
* Subjects with contra-indications to MR imaging, including pacemakers or claustrophobia; * Evidence of large vessel stroke or mass lesion on MRI * Regular use of anti-cholinergic, benzodiazepines or neuroleptic drugs * History of significant GI disease * Significant metabolic or uncontrolled medical comorbidity * Poorly controlled diabetes * Pregnancy or breast feeding * Dementia requiring informed assent * Suicidal ideation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Whole Brain Butyrate PET Radiotracer Binding | Pre and Post approximately 30 days of intervention | Whole-brain butyrate distribution volume ratios (DVRs) were computed relative to a cerebral white matter reference region pre and post approximately 30 days of open-label treatment with tributyrin. Lower radiotracer binding is interpreted to reflect higher levels of (non-tracer) butyrate in the brain, whereas higher radiotracer binding reflects higher butyrate receptor binding site availability, indicating lower levels of non-tracer butyrate in the brain. |
| Glucose Metabolism | Pre and Post approximately 30 days of intervention | Continuous glucose meter 7-10-day average glucose readings before/after open-label treatment with the SCFA prodrug tributyrin in patients with PD and normal controls. Healthy fasting blood glucose ranges from 70 to 99 milligrams per deciliter (mg/dL), with a healthy maximum of 180 mg/dL withing 2 hours of eating meals. |
Countries
United States
Participant flow
Pre-assignment details
18 participants were enrolled in the study. One Parkinson's disease subject withdrew prior to beginning study procedures and thus is not counted as started.
Participants by arm
| Arm | Count |
|---|---|
| Parkinson's Disease Tributyrin Intervention Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.
tributyrin: Post-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days. | 14 |
| Healthy Control Tributyrin Intervention Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.
tributyrin: Post-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days. | 3 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Parkinson's Disease Tributyrin Intervention | Healthy Control Tributyrin Intervention | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 2 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 1 Participants | 6 Participants |
| Age, Continuous | 66.4 years STANDARD_DEVIATION 5.7 | 67.3 years STANDARD_DEVIATION 10.6 | 66.5 years STANDARD_DEVIATION 6.4 |
| Education | 17.9 years STANDARD_DEVIATION 2.8 | 19.3 years STANDARD_DEVIATION 3.5 | 18.1 years STANDARD_DEVIATION 2.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 3 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Montreal Cognitive Assessment (MoCA) | 26.8 units on a scale STANDARD_DEVIATION 2.9 | 27.7 units on a scale STANDARD_DEVIATION 1.2 | 26.9 units on a scale STANDARD_DEVIATION 2.7 |
| Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III | 46.9 units on a scale STANDARD_DEVIATION 12.7 | 28.0 units on a scale STANDARD_DEVIATION 20.5 | 43.6 units on a scale STANDARD_DEVIATION 15.5 |
| Parkinson's Disease Cognitive Rating Scale (PDCRS) | 92.0 units on a scale STANDARD_DEVIATION 12.3 | 96.3 units on a scale STANDARD_DEVIATION 3.8 | 92.8 units on a scale STANDARD_DEVIATION 11.3 |
| 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 | 14 Participants | 3 Participants | 17 Participants |
| Region of Enrollment United States | 14 participants | 3 participants | 16 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 1 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 3 |
| other Total, other adverse events | 13 / 14 | 2 / 3 |
| serious Total, serious adverse events | 0 / 14 | 0 / 3 |
Outcome results
Primary
Glucose Metabolism
Continuous glucose meter 7-10-day average glucose readings before/after open-label treatment with the SCFA prodrug tributyrin in patients with PD and normal controls. Healthy fasting blood glucose ranges from 70 to 99 milligrams per deciliter (mg/dL), with a healthy maximum of 180 mg/dL withing 2 hours of eating meals.
Time frame: Pre and Post approximately 30 days of intervention
Population: 2 Parkinson's disease participants did not complete continuous glucose monitoring due to scheduling conflicts, thus only 14/16 participants were included in this analysis. Healthy control sample size (n=2) was not sufficient to perform statistical analysis for that group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Parkinson's Disease Tributyrin Intervention | Glucose Metabolism | Pre-Intervention | 135.00 milligrams per deciliter (mg/dL) | Standard Deviation 49.39 |
| Parkinson's Disease Tributyrin Intervention | Glucose Metabolism | Post-Intervention | 139.33 milligrams per deciliter (mg/dL) | Standard Deviation 53.31 |
| Healthy Control Tributyrin Intervention | Glucose Metabolism | Pre-Intervention | 104.50 milligrams per deciliter (mg/dL) | Standard Deviation 3.54 |
| Healthy Control Tributyrin Intervention | Glucose Metabolism | Post-Intervention | 125.00 milligrams per deciliter (mg/dL) | Standard Deviation 4.24 |
p-value: 0.2795% CI: [-3.81, 12.47]t-test, 2 sided
Primary
Whole Brain Butyrate PET Radiotracer Binding
Whole-brain butyrate distribution volume ratios (DVRs) were computed relative to a cerebral white matter reference region pre and post approximately 30 days of open-label treatment with tributyrin. Lower radiotracer binding is interpreted to reflect higher levels of (non-tracer) butyrate in the brain, whereas higher radiotracer binding reflects higher butyrate receptor binding site availability, indicating lower levels of non-tracer butyrate in the brain.
Time frame: Pre and Post approximately 30 days of intervention
Population: Brain imaging was not strictly required for participation in the remaining components of the study. Not all participants underwent PET imaging. Healthy control sample size (n=2) was not sufficient to perform statistical analysis for that group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Parkinson's Disease Tributyrin Intervention | Whole Brain Butyrate PET Radiotracer Binding | Pre-intervention | 1.81 Parametric DVR | Standard Deviation 0.1 |
| Parkinson's Disease Tributyrin Intervention | Whole Brain Butyrate PET Radiotracer Binding | Post-intervention | 1.73 Parametric DVR | Standard Deviation 0.1 |
| Healthy Control Tributyrin Intervention | Whole Brain Butyrate PET Radiotracer Binding | Pre-intervention | 1.79 Parametric DVR | Standard Deviation 0.02 |
| Healthy Control Tributyrin Intervention | Whole Brain Butyrate PET Radiotracer Binding | Post-intervention | 1.74 Parametric DVR | Standard Deviation 0.01 |
p-value: 0.00595% CI: [-0.12, -0.03]t-test, 2 sided