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

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

Study Overview

• Status: Terminated
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: tributyrin

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parkinson's Disease Tributyrin Intervention; Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.	Drug: tributyrin; Post-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.
Experimental: Healthy Control Tributyrin Intervention; Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.	Drug: tributyrin; Post-biotic short chain fatty acid dietary supplement. Participants will take 500mg TID tributyrin supplement for 30 days +/- 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FDG glucose PET brain	Brain PET glucose radiotracer binding	after approximately 30 days of intervention
butyrate PET brain	butyrate PET radiotracer binding	after approximately 30 days of intervention
Montreal Cognitive Assessment cognitive rating scale (MoCa)	Montreal Cognitive Assessment cognitive rating scale is a cognitive assessment with scores ranging from 0-30, with higher scores indicating better cognitive function.	after approximately 30 days of intervention

Collaborators and Investigators

• Sponsor: Nicolaas Bohnen, MD, PhD
• Investigators: Principal Investigator: Nicolaas I Bohnen, MD, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): September 26, 2023
• Study Completion (Actual): September 26, 2023

Study Registration Dates

• First Submitted: July 1, 2022
• First Submitted That Met QC Criteria: July 1, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: functional neuroimaging; butyrate; short chain fatty acid; tributyrin
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: HUM00211320

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No