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TerminatedNCT05446168BUTTERUpdated Jan 23, 2025Results posted

Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Tributyrin Supplementation

A Phase 1 interventional study of tributyrin in Parkinson Disease, sponsored by Nicolaas Bohnen, MD, PhD. Terminated at 1 site in United States. Open to participants aged 45 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-01-23.

Sponsored by Nicolaas Bohnen, MD, PhD · Phase 1, Interventional, and Treatment

Why this study was terminated
Withdrawal of funding
Phase
Phase 1
Study type
Interventional
Enrollment
18
Allocation
Non-randomized
Ages
45 Years and older
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • Parkinson Disease

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Keywords

  • short chain fatty acid
  • butyrate
  • tributyrin
  • functional neuroimaging
03

Who can participate

Ages eligible
45 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Healthy control volunteers over 45 years of age
  • People with Parkinson Disease over 45 years of age

Exclusion criteria

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
18 participants (actual)

Study arms

  • Experimental
    Parkinson's Disease Tributyrin Intervention

    Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.

    Drug: tributyrin

  • Experimental
    Healthy Control Tributyrin Intervention

    Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.

    Drug: tributyrin

Interventions

  • Drugtributyrin

    Post-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

06

Results

Posted Jan 23, 2025

Participant flow

Participant flow — Overall Study
MilestoneParkinson's Disease Tributyrin InterventionHealthy Control Tributyrin Intervention
Started143
Completed142
Not completed01
Withdrew: Physician decision01

Outcome measures

PrimaryWhole 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
Reported as:
Mean · Parametric DVR
Whole Brain Butyrate PET Radiotracer Binding
Parametric DVRParkinson's Disease Tributyrin InterventionHealthy Control Tributyrin Intervention
Pre-intervention1.81 ± 0.101.79 ± 0.02
Post-intervention1.73 ± 0.101.74 ± 0.01
Statistical analysis
  • Parkinson's Disease Tributyrin Intervention · t-test, 2 sided · p = 0.005 (A priori threshold for statistical significance is p \< 0.05.) · Mean difference (net): -0.08 · 95% CI -0.12 to -0.03t = -4.05, df = 7
PrimaryGlucose 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
Reported as:
Mean · milligrams per deciliter (mg/dL)
Glucose Metabolism
milligrams per deciliter (mg/dL)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin Intervention
Pre-Intervention135.00 ± 49.39104.50 ± 3.54
Post-Intervention139.33 ± 53.31125.00 ± 4.24
Statistical analysis
  • Parkinson's Disease Tributyrin Intervention · t-test, 2 sided · p = 0.27 (A priori threshold for statistical significance is p \< 0.05.) · Mean difference (net): 4.33 · 95% CI -3.81 to 12.47t = 1.17, df = 11

Adverse events

Collected over For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Parkinson's Disease Tributyrin Intervention0/14 (0%)0/14 (0%)13/14 (92.9%)
Healthy Control Tributyrin Intervention0/3 (0%)0/3 (0%)2/3 (66.7%)
Most frequent other events
Showing 10 of 13
Most frequent other events
EventParkinson's Disease Tributyrin InterventionHealthy Control Tributyrin Intervention
GI DiscomfortGastrointestinal disorders7/140/3
Behavioral DisturbancePsychiatric disorders0/141/3
HeadacheNervous system disorders0/141/3
Respiratory InfectionInfections and infestations4/140/3
Sleep DisruptionNervous system disorders3/140/3
Shakiness/DyskinesiaNervous system disorders2/140/3
Urinary Tract InfectionInfections and infestations2/140/3
Toe InjuryInjury, poisoning and procedural complications1/140/3
ClaustrophobiaPsychiatric disorders1/140/3
Gait DisturbancesNervous system disorders1/140/3

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin InterventionTotal
<=18 years000
Between 18 and 65 years516
>=65 years9211
Age, Continuous
Age, Continuous(years)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin InterventionTotal
Mean66.4 ± 5.767.3 ± 10.666.5 ± 6.4
Sex: Female, Male
Sex: Female, Male(Participants)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin InterventionTotal
Female527
Male9110
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin InterventionTotal
Hispanic or Latino000
Not Hispanic or Latino14317
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin InterventionTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White14317
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin InterventionTotal
United States14316
Education
Education(years)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin InterventionTotal
Mean17.9 ± 2.819.3 ± 3.518.1 ± 2.9
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III(units on a scale)Parkinson's Disease Tributyrin InterventionHealthy Control Tributyrin InterventionTotal
Mean46.9 ± 12.728.0 ± 20.543.6 ± 15.5

2 further baseline measures are reported on the registry.

07

Study locations

1 site
  • University of Michigan Health System Functional Neuroimaging, Cognitive and Mobility Laboratory
    Ann Arbor, Michigan 48106, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jul 23, 2024
  • Informed consent form · Mar 9, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT05446168
Lead sponsor
Nicolaas Bohnen, MD, PhD
Responsible party
Nicolaas Bohnen, MD, PhD (Professor of Radiology, University of Michigan) — Sponsor-investigator
First posted
Jul 6, 2022
Start date
Jul 1, 2022
Primary completion
Sep 26, 2023
Completion
Sep 26, 2023
Results posted
Jan 23, 2025
Last update
Jan 23, 2025

Study contacts

Nicolaas I Bohnen, MD, PhD
principal investigator · University of Michigan

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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