Parkinson DiseasePhase 1/2BUTTER2NCT07154511
Phase 2 Trial of Tributyrin in People With Parkinson's Disease and Cognitive Impairments
A Phase 1/2 study testing Tributyrin in people with Parkinson Disease and Parkinson Disease Dementia, run by Prabesh Kanel at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn if taking a tributyrin supplement works to improve memory and thinking and walking and balance in adults with Parkinson disease Parkinson disease dementia. It will also learn about the safety of tributyrin supplementation. The main questions it aims to answer are: 1. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Parkinson Disease, Parkinson Disease Dementia
- What is being tested?
- Tributyrin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Nov 2025to May 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or Female, age 45 years and over.
- Diagnosis of PD based on the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Research Criteria (Hughes et al., 1992) AND evidence of mild cognitive impairment (Litvan et al., 2012) OR Diagnosis of PDD (Emre et al., 2007).
- If taking cholinesterase inhibitors, benzodiazepines, memantine, or anti-psychotic medications, on a stable regimen as defined by no medication changes for these drugs in prior 4 weeks.
Who cannot join
- Evidence of atypical parkinsonism.
- Contra-indications to MR imaging including but not limited to pacemakers, aneurysm clips, intraocular metal, cochlear implant, or severe claustrophobia.
- Evidence of large vessel stroke or mass lesion on MRI.
- Regular use of typical anti-cholinergic drugs.
- Recent history of significant, uncontrolled GI disease such as GERD, colorectal cancer.
- Significant metabolic or uncontrolled medical comorbidity.
Show all 9Show fewer
- Pregnant or nursing.
- Suicidal ideation, as indicated by a response of 2 or 3 on question 9 of the Beck Depression Inventory.
- Any other condition or criterion that would preclude safe and meaningful participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Domino's Farms
Ann Arbor, Michigan, 48105
Robert Vangel, BSc, 734-936-1168, rvangel@med.umich.edu
Prabesh Kanel, PhD
About this study
The goal of this clinical trial is to learn if taking a tributyrin supplement works to improve memory and thinking and walking and balance in adults with Parkinson disease Parkinson disease dementia. It will also learn about the safety of tributyrin supplementation. The main questions it aims to answer are:
- Does tributyrin improve memory/thinking test scores and walking/balance ability?
- What medical problems do participants have when taking tributyrin?
Read more
Researchers will compare tributyrin to a placebo (a look-alike substance that contains no drug) to see if tributyrin works to treat Parkinson disease symptoms.
Participants will:
- Take tributyrin 3 times a day for 80-100 days
- Complete motor and cognitive testing at the clinic before and after the supplementation period
- Complete brain imaging (MRI scans and PET scans) before and after the supplementation period.
Read the detailed description
Changes in cognition, progressing usually to dementia, are common features of Parkinson disease (PD). These debilitating impairments respond poorly to current anti-dementia treatments and call for novel strategies. Short chain fatty acids (SFCA), in particular butyric acid (BA), are naturally present in the colon as a bacterial product of dietary fiber fermentation. There is renewed interest in SCFAs because of their potential as alternative substrates in brain metabolism, their role in the gut-brain axis, and emerging evidence that interventions promoting SCFA benefit patients with neurodegenerative disorders. Convergent evidence suggests that SFCAs may ameliorate metabolic defects secondary to mitochondrial abnormalities in PD. In addition, the gut-brain axis represents a bidirectional communication complex system involving the vagal and sympathetic nerves and humoral systems. Effects of SCFA on the brain may be indirect and/or direct. For example, fiber-induced SCFA production in the colon may result in vagal nerve-mediated changes affecting the brain. Blood and brain levels of fiber-induced SCFA are naturally very low. SCFAs can be directly administered orally, resulting in higher portal vein and systemic plasma levels that may more potently affect brain functions. Oral butyrate supplementation, however, suffers from several limitations as plasma levels are low because of rapid metabolism. In contrast, tributyrin (the triglyceride of BA) is rapidly absorbed and chemically stable in plasma, diffuses through biological membranes and is metabolized by intracellular lipases, releasing therapeutically effective BA over time directly within cells. We previously generated target engagement data showing that oral tributyrin, 500 mg three times per day (tid) po, is well tolerated and improves cognition. We also conducted the first [11C]butyrate positron emission tomography (PET) study, demonstrating that tributyrin has direct brain effects, particularly in regions relevant to cognitive functions. Significant systemic anti-inflammatory effects were also observed. A limitation of our preliminary phase 1I target engagement study is the short duration (30 days) and lack of inclusion of people with PD with more severe cognitive impairments, such as dementia. The overarching goal of this project is to perform a parallel group, double-blinded, randomized placebo-controlled phase 2 clinical trial of tributyrin, 500 mg tid po for 90 days, to validate and extend these preliminary observations in a longer duration clinical trial in people with PD with mild cognitive impairment (PD-MCI) or Parkinson disease dementia (PDD). There is critical unmet clinical need to treat people currently affected with PD who have significant cognitive impairments. Our main hypothesis is that oral tributyrin supplementation will improve cognition as well as motor functions, including cognition-dependent postural instability and gait difficulties. Successful completion of this trial would set the stage for a major, multi-center phase III clinical trial aimed at ameliorating this particularly morbid feature of PD.
- Conditions
- Parkinson Disease, Parkinson Disease Dementia
- Being tested
- Tributyrin, Placebo
- Keywords
- short chain fatty acid, butyrate, tributyrin, functional neuroimaging
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TributyrinDrug
Post-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 90 days +/- 7 days.
PlaceboDrug
Participants will take 500mg TID placebo for 90 days +/- 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Tributyrin Supplementation | Experimental | Participants will take 500mg TID tributyrin supplement for 90 days +/- 7 days. Receives: Drug: Tributyrin |
| Placebo | Placebo comparator | Participants will take 500mg placebo for 90 days +/- 7 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Single composite global cognitive z-score
A global cognitive z-score derived from a neuropsychological battery including the California Verbal Learning Test (short- and long-term memory), Delis-Kaplan Executive Function System (verbal fluency via letter fluency test, executive function via Stroop and Trail Making Test Part 4), and Benton Judgment of Line Orientation Test (visuospatial cognition). Individual test scores are normatively z-scored with age- and sex-adjustment using data from 55 cognitively normal controls (Montreal Cognitive Assessment score > 25). All z-scores are aligned so that higher scores indicate better performance. Scores are averaged within domains and then across domains to compute the global cognitive z-score.
Measured: Baseline and post-intervention (83-97 days after starting supplement)
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III Score
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS part III) is the motor examination portion of the UPDRS evaluation. Scores range from 0-132, with higher scores indicating greater severity of motor symptoms.
Measured: Baseline and post-intervention (83-97 days after starting supplement)
Safety and tolerability of tributyrin
Safety and tolerability are assessed by monitoring the incidence, severity, and relationship of adverse events (AEs), serious adverse events (SAEs), and discontinuations due to AEs. AE information via biweekly phone-call monitoring, and during the post-intervention study visit.
Measured: During and after 83-97 day supplementation period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2025
- Study start7 Nov 2025
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
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.
- 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prabesh Kanel
- Sponsor type
- University, hospital or other
- Collaborators
- Farmer Family Foundation
- Responsible party
- Sponsor-investigator, Prabesh Kanel, University of Michigan
- Investigators
- Prabesh Kanel, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07154511
- Sponsor's protocol ID
- HUM00270219
- Acronym
- BUTTER2
- Status last verified
- Nov 2025
- First submitted
- 26 Aug 2025
- Last updated
- 12 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Tributyrin in People With Parkinson's Disease and Cognitive Impairments
- ClinicalTrials.gov ID
- NCT07154511
- Acronym / sponsor ID
- BUTTER2 / HUM00270219
- Conditions
- Parkinson Disease, Parkinson Disease Dementia
- Keywords
- short chain fatty acid, butyrate, tributyrin, functional neuroimaging
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Prabesh KanelUniversity, hospital or other
- Collaborators
- Farmer Family Foundation
- Study start
- 7 Nov 2025 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 4 Sep 2025 (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.
The goal of this clinical trial is to learn if taking a tributyrin supplement works to improve memory and thinking and walking and balance in adults with Parkinson disease Parkinson disease dementia. It will also learn about the safety of tributyrin supplementation. The main questions it aims to answer are:
- Does tributyrin improve memory/thinking test scores and walking/balance ability?
- What medical problems do participants have when taking tributyrin?
Researchers will compare tributyrin to a placebo (a look-alike substance that contains no drug) to see if tributyrin works to treat Parkinson disease symptoms.
Participants will:
- Take tributyrin 3 times a day for 80-100 days
- Complete motor and cognitive testing at the clinic before and after the supplementation period
- Complete brain imaging (MRI scans and PET scans) before and after the supplementation period.
Detailed description
Changes in cognition, progressing usually to dementia, are common features of Parkinson disease (PD). These debilitating impairments respond poorly to current anti-dementia treatments and call for novel strategies. Short chain fatty acids (SFCA), in particular butyric acid (BA), are naturally present in the colon as a bacterial product of dietary fiber fermentation. There is renewed interest in SCFAs because of their potential as alternative substrates in brain metabolism, their role in the gut-brain axis, and emerging evidence that interventions promoting SCFA benefit patients with neurodegenerative disorders. Convergent evidence suggests that SFCAs may ameliorate metabolic defects secondary to mitochondrial abnormalities in PD. In addition, the gut-brain axis represents a bidirectional communication complex system involving the vagal and sympathetic nerves and humoral systems. Effects of SCFA on the brain may be indirect and/or direct. For example, fiber-induced SCFA production in the colon may result in vagal nerve-mediated changes affecting the brain. Blood and brain levels of fiber-induced SCFA are naturally very low. SCFAs can be directly administered orally, resulting in higher portal vein and systemic plasma levels that may more potently affect brain functions. Oral butyrate supplementation, however, suffers from several limitations as plasma levels are low because of rapid metabolism. In contrast, tributyrin (the triglyceride of BA) is rapidly absorbed and chemically stable in plasma, diffuses through biological membranes and is metabolized by intracellular lipases, releasing therapeutically effective BA over time directly within cells. We previously generated target engagement data showing that oral tributyrin, 500 mg three times per day (tid) po, is well tolerated and improves cognition. We also conducted the first [11C]butyrate positron emission tomography (PET) study, demonstrating that tributyrin has direct brain effects, particularly in regions relevant to cognitive functions. Significant systemic anti-inflammatory effects were also observed. A limitation of our preliminary phase 1I target engagement study is the short duration (30 days) and lack of inclusion of people with PD with more severe cognitive impairments, such as dementia. The overarching goal of this project is to perform a parallel group, double-blinded, randomized placebo-controlled phase 2 clinical trial of tributyrin, 500 mg tid po for 90 days, to validate and extend these preliminary observations in a longer duration clinical trial in people with PD with mild cognitive impairment (PD-MCI) or Parkinson disease dementia (PDD). There is critical unmet clinical need to treat people currently affected with PD who have significant cognitive impairments. Our main hypothesis is that oral tributyrin supplementation will improve cognition as well as motor functions, including cognition-dependent postural instability and gait difficulties. Successful completion of this trial would set the stage for a major, multi-center phase III clinical trial aimed at ameliorating this particularly morbid feature of PD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tributyrin Supplementation | Experimental | Drug: TributyrinParticipants will take 500mg TID tributyrin supplement for 90 days +/- 7 days. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will take 500mg placebo for 90 days +/- 7 days. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or Female, age 45 years and over.
- Diagnosis of PD based on the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Research Criteria (Hughes et al., 1992) AND evidence of mild cognitive impairment (Litvan et al., 2012) OR Diagnosis of PDD (Emre et al., 2007).
- If taking cholinesterase inhibitors, benzodiazepines, memantine, or anti-psychotic medications, on a stable regimen as defined by no medication changes for these drugs in prior 4 weeks.
Key exclusion criteria (9 listed)
- Evidence of atypical parkinsonism.
- Contra-indications to MR imaging including but not limited to pacemakers, aneurysm clips, intraocular metal, cochlear implant, or severe claustrophobia.
- Evidence of large vessel stroke or mass lesion on MRI.
- Regular use of typical anti-cholinergic drugs.
- Recent history of significant, uncontrolled GI disease such as GERD, colorectal cancer.
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 |
|---|---|---|
| TributyrinPost-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 90 days +/- 7 days. | Drug | Tributyrin Supplementation |
| PlaceboParticipants will take 500mg TID placebo for 90 days +/- 7 days. | Drug | Placebo |
Primary outcome
Single composite global cognitive z-score
Time frame: Baseline and post-intervention (83-97 days after starting supplement)
A global cognitive z-score derived from a neuropsychological battery including the California Verbal Learning Test (short- and long-term memory), Delis-Kaplan Executive Function System (verbal fluency via letter fluency test, executive function via Stroop and Trail Making Test Part 4), and Benton Judgment of Line Orientation Test (visuospatial cognition). Individual test scores are normatively z-scored with age- and sex-adjustment using data from 55 cognitively normal controls (Montreal Cognitive Assessment score > 25). All z-scores are aligned so that higher scores indicate better performance. Scores are averaged within domains and then across domains to compute the global cognitive z-score.
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III Score
Time frame: Baseline and post-intervention (83-97 days after starting supplement)
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS part III) is the motor examination portion of the UPDRS evaluation. Scores range from 0-132, with higher scores indicating greater severity of motor symptoms.
Safety and tolerability of tributyrin
Time frame: During and after 83-97 day supplementation period
Safety and tolerability are assessed by monitoring the incidence, severity, and relationship of adverse events (AEs), serious adverse events (SAEs), and discontinuations due to AEs. AE information via biweekly phone-call monitoring, and during the post-intervention study visit.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2025.
- Individual participant dataSharing planned: No
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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.
Prabesh Kanel, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tributyrin in people with Parkinson Disease and Parkinson Disease Dementia, run by Prabesh Kanel 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 3 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 12 Nov 2025. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Robert Vangel, BSc (734-936-1168, rvangel@med.umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Single composite global cognitive z-score (time frame: Baseline and post-intervention (83-97 days after starting supplement)). The study lists 3 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 12 Nov 2025.