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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Parkinson's Disease Tributyrin Intervention | Experimental | Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days. |
|
| Healthy Control Tributyrin Intervention | Experimental | Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tributyrin | Drug | Post-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Pre and Post approximately 30 days of intervention |
| 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. | Pre and Post approximately 30 days of intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicolaas I Bohnen, MD, PhD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Health System Functional Neuroimaging, Cognitive and Mobility Laboratory | Ann Arbor | Michigan | 48106 | United States |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Healthy Control Tributyrin Intervention |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | Parametric DVR | Pre and Post approximately 30 days of intervention |
|
For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| GI Discomfort | Gastrointestinal disorders | Systematic Assessment | Related, mild, expected AE |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nicolaas Bohnen, MD, PhD | University of Michigan | 734-936-1168 | nbohnen@umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 23, 2024 | Aug 23, 2024 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 9, 2023 | Nov 1, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C005830 | tributyrin |
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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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Education | Mean | Standard Deviation | years |
|
| Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III | The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3 is a clinician-administered motor exam consisting of 18 items to evaluate the motor symptom severity in Parkinson's disease. Total scores range from 0 to 132, with higher scores indicating higher severity of motor symptoms. MDS-UPDRS Part 3 scores of 32 and below are typically considered mild, 33-58 is moderate, and 59 and above considered severe. | Mean | Standard Deviation | units on a scale |
|
| Montreal Cognitive Assessment (MoCA) | The Montreal Cognitive Assessment (MoCA) is used for detection of mild cognitive impairment. It assesses short-term memory, visuospatial abilities, executive functioning, attention, language, and orientation. Scores range from 0 to 30, with low scores indicating more cognitive impairment. Scores of 26 and above indicate normal cognitive performance, 18-25 indicate mild impairment, 10-17 indicate moderate impairment, and 0-9 indicate severe impairment. | Mean | Standard Deviation | units on a scale |
|
| Parkinson's Disease Cognitive Rating Scale (PDCRS) | The Parkinson's Disease Cognitive Rating Scale (PDCRS) evaluates cognition in Parkinson's disease. Scores range from 0-134 with lower scores indicating increased cognitive impairment. | Mean | Standard Deviation | units on a scale |
|
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.
| OG001 | 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. |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | milligrams per deciliter (mg/dL) | Pre and Post approximately 30 days of intervention |
|
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 13 |
| 14 |
| EG001 | 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. | 0 | 3 | 0 | 3 | 2 | 3 |
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| Behavioral Disturbance | Psychiatric disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Headache | Nervous system disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Sleep Disruption | Nervous system disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Shakiness/Dyskinesia | Nervous system disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Toe Injury | Injury, poisoning and procedural complications | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Claustrophobia | Psychiatric disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Respiratory Infection | Infections and infestations | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Urinary Tract Infection | Infections and infestations | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Gait Disturbances | Nervous system disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Leg Swelling | Vascular disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| High Blood Glucose | Metabolism and nutrition disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Unrelated, mild, unexpected AE |
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| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |