Trial Outcomes & Findings for Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Tributyrin Supplementation (NCT NCT05446168)

Last Updated: 2025-01-23

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

Pre and Post approximately 30 days of intervention

Results posted on

2025-01-23

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	14	3
Overall Study COMPLETED	14	2
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Physician Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Parkinson's Disease Tributyrin Intervention n=14 Participants 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.	Healthy Control Tributyrin Intervention n=3 Participants 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.	Total n=17 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	66.4 years STANDARD_DEVIATION 5.7 • n=5 Participants	67.3 years STANDARD_DEVIATION 10.6 • n=7 Participants	66.5 years STANDARD_DEVIATION 6.4 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	3 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	3 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	3 participants n=7 Participants	16 participants n=5 Participants
Education	17.9 years STANDARD_DEVIATION 2.8 • n=5 Participants	19.3 years STANDARD_DEVIATION 3.5 • n=7 Participants	18.1 years STANDARD_DEVIATION 2.9 • n=5 Participants
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III	46.9 units on a scale STANDARD_DEVIATION 12.7 • n=5 Participants	28.0 units on a scale STANDARD_DEVIATION 20.5 • n=7 Participants	43.6 units on a scale STANDARD_DEVIATION 15.5 • n=5 Participants
Montreal Cognitive Assessment (MoCA)	26.8 units on a scale STANDARD_DEVIATION 2.9 • n=5 Participants	27.7 units on a scale STANDARD_DEVIATION 1.2 • n=7 Participants	26.9 units on a scale STANDARD_DEVIATION 2.7 • n=5 Participants
Parkinson's Disease Cognitive Rating Scale (PDCRS)	92.0 units on a scale STANDARD_DEVIATION 12.3 • n=5 Participants	96.3 units on a scale STANDARD_DEVIATION 3.8 • n=7 Participants	92.8 units on a scale STANDARD_DEVIATION 11.3 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Parkinson's Disease Tributyrin Intervention n=8 Participants 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.	Healthy Control Tributyrin Intervention n=2 Participants 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.
Whole Brain Butyrate PET Radiotracer Binding Pre-intervention	1.81 Parametric DVR Standard Deviation 0.10	1.79 Parametric DVR Standard Deviation 0.02
Whole Brain Butyrate PET Radiotracer Binding Post-intervention	1.73 Parametric DVR Standard Deviation 0.10	1.74 Parametric DVR Standard Deviation 0.01

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Parkinson's Disease Tributyrin Intervention n=12 Participants 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.	Healthy Control Tributyrin Intervention n=2 Participants 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.
Glucose Metabolism Post-Intervention	139.33 milligrams per deciliter (mg/dL) Standard Deviation 53.31	125.00 milligrams per deciliter (mg/dL) Standard Deviation 4.24
Glucose Metabolism Pre-Intervention	135.00 milligrams per deciliter (mg/dL) Standard Deviation 49.39	104.50 milligrams per deciliter (mg/dL) Standard Deviation 3.54

Adverse Events

Parkinson's Disease Tributyrin Intervention

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Healthy Control Tributyrin Intervention

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Parkinson's Disease Tributyrin Intervention n=14 participants at risk 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.	Healthy Control Tributyrin Intervention n=3 participants at risk 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.
Gastrointestinal disorders GI Discomfort	50.0% 7/14 • Number of events 8 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Psychiatric disorders Behavioral Disturbance	0.00% 0/14 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	33.3% 1/3 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Nervous system disorders Headache	0.00% 0/14 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	33.3% 1/3 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Nervous system disorders Sleep Disruption	21.4% 3/14 • Number of events 3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Nervous system disorders Shakiness/Dyskinesia	14.3% 2/14 • Number of events 2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Injury, poisoning and procedural complications Toe Injury	7.1% 1/14 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Psychiatric disorders Claustrophobia	7.1% 1/14 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Infections and infestations Respiratory Infection	28.6% 4/14 • Number of events 4 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Infections and infestations Urinary Tract Infection	14.3% 2/14 • Number of events 2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Nervous system disorders Gait Disturbances	7.1% 1/14 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Vascular disorders Leg Swelling	7.1% 1/14 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Metabolism and nutrition disorders High Blood Glucose	7.1% 1/14 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Respiratory, thoracic and mediastinal disorders Shortness of breath	7.1% 1/14 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.

Additional Information

Nicolaas Bohnen, MD, PhD

University of Michigan

Phone: 734-936-1168

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place