Trial Outcomes & Findings for Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones (NCT NCT05778695)

Last Updated: 2025-02-12

Results Overview

Continuous glucose meter 7-10-day average glucose readings before/after open-label treatment with the ketone ester in patients with PD, Parkinson's disease dementia/Lewy body dementia, 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 within 2 hours of eating meals.

Recruitment status

TERMINATED

Study phase

Target enrollment

16 participants

Primary outcome timeframe

Pre and post approximately 30 days of intervention

Results posted on

2025-02-12

Participant Flow

16 participants were enrolled in the study. There were no withdrawals.

Participant milestones

Participant milestones
Measure	Parkinson Disease Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Parkinson Disease Dementia/Lewy Body Dementia Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) TID as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Healthy Controls Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) TID as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)
Overall Study STARTED	4	10	2
Overall Study COMPLETED	4	10	2
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Parkinson Disease n=4 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Parkinson Disease Dementia/Lewy Body Dementia n=10 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) TID as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Healthy Controls n=2 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) TID as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Total n=16 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	10 Participants n=7 Participants	2 Participants n=5 Participants	16 Participants n=4 Participants
Age, Continuous	77 years STANDARD_DEVIATION 4.03 • n=5 Participants	74.5 years STANDARD_DEVIATION 4.93 • n=7 Participants	70 years STANDARD_DEVIATION 1.41 • n=5 Participants	74.63 years STANDARD_DEVIATION 4.76 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	10 Participants n=7 Participants	2 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	10 Participants n=7 Participants	2 Participants n=5 Participants	16 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	10 Participants n=7 Participants	2 Participants n=5 Participants	16 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	4 participants n=5 Participants	10 participants n=7 Participants	2 participants n=5 Participants	16 participants n=4 Participants
Education	19.0 years STANDARD_DEVIATION 3.56 • n=5 Participants	16.7 years STANDARD_DEVIATION 4.52 • n=7 Participants	17.0 years STANDARD_DEVIATION 1.41 • n=5 Participants	17.31 years STANDARD_DEVIATION 4.00 • n=4 Participants
Modified Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRSIII)	46.00 units on a scale STANDARD_DEVIATION 5.90 • n=5 Participants	47.80 units on a scale STANDARD_DEVIATION 11.22 • n=7 Participants	6.75 units on a scale STANDARD_DEVIATION 9.55 • n=5 Participants	44.23 units on a scale STANDARD_DEVIATION 16.76 • n=4 Participants
Montreal Cognitive Assessment (MoCA)	22.25 units on a scale STANDARD_DEVIATION 4.27 • n=5 Participants	17.00 units on a scale STANDARD_DEVIATION 7.41 • n=7 Participants	24.00 units on a scale STANDARD_DEVIATION 1.41 • n=5 Participants	19.19 units on a scale STANDARD_DEVIATION 6.75 • n=4 Participants
Parkinson's Disease Cognitive Rating Scale (PDCRS)	66.75 units on a scale STANDARD_DEVIATION 16.13 • n=5 Participants	48.50 units on a scale STANDARD_DEVIATION 25.31 • n=7 Participants	79.00 units on a scale STANDARD_DEVIATION 7.07 • n=5 Participants	56.88 units on a scale STANDARD_DEVIATION 24.04 • n=4 Participants

PRIMARY outcome

Timeframe: Pre and post approximately 30 days of intervention

Population: 13 of the 16 participants completed continuous glucose monitoring. The remaining 3 participants did not complete continuous glucose monitoring due to device availability and ability to understand instructions. Healthy control sample size (n=2) was not sufficient to perform statistical analysis for that group.

Outcome measures

Outcome measures
Measure	Parkinson Disease n=4 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Parkinson Disease Dementia/Lewy Body Dementia n=7 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Healthy Controls n=2 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)
Glucose Metabolism Pre-intervention	133.0 milligrams per deciliter (mg/dL) Standard Deviation 20.30	134.86 milligrams per deciliter (mg/dL) Standard Deviation 24.30	179.50 milligrams per deciliter (mg/dL) Standard Deviation 19.09
Glucose Metabolism Post-intervention	128.25 milligrams per deciliter (mg/dL) Standard Deviation 18.26	132.86 milligrams per deciliter (mg/dL) Standard Deviation 33.42	170.50 milligrams per deciliter (mg/dL) Standard Deviation 21.92

PRIMARY outcome

Timeframe: Pre and post approximately 30 days of intervention

Population: All participants completed CDR before and after intervention. There was no change in CDR scores in the Parkinson's disease group, and the Healthy Control group had insufficient sample size (n = 2) to perform any statistical analysis.

The clinical dementia rating scale is a measure of functional and cognitive performance relevant to dementia. It is scored from 0 (normal) to 3 (severe dementia). The clinical dementia rating scale will be assessed in patients with Parkinson's disease, Parkinson's disease dementia/Lewy body dementia, and healthy controls before and after open-label treatment with the ketone ester.

Outcome measures

Outcome measures
Measure	Parkinson Disease n=4 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Parkinson Disease Dementia/Lewy Body Dementia n=10 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Healthy Controls n=2 Participants Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)
Clinical Dementia Rating Scale Score Pre-intervention	0.5 score on a scale Standard Deviation 0.41	1.0 score on a scale Standard Deviation 0.85	0 score on a scale Standard Deviation 0
Clinical Dementia Rating Scale Score Post-intervention	0.5 score on a scale Standard Deviation 0.41	1.15 score on a scale Standard Deviation 0.88	0.25 score on a scale Standard Deviation 0.35

Adverse Events

Parkinson Disease

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Parkinson Disease Dementia/Lewy Body Dementia

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Healthy Controls

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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

Measure	Parkinson Disease n=4 participants at risk Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Parkinson Disease Dementia/Lewy Body Dementia n=10 participants at risk Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)	Healthy Controls n=2 participants at risk Participants will take the ketone ester supplement for 30 days +/- 7 days. For days 1 through 7, participants will take 12.5g (25mL) of the ketone ester supplement (KetoneAid) TID, and on day 8, the dose will be increased to 25g (50mL) three times daily (TID) as tolerated. KE dose will be titrated down to a tolerated level if necessary. Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate: Ketone ester (KE) dietary supplement (KetoneAid)
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/4 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Ear and labyrinth disorders Ear Infection	0.00% 0/4 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Injury, poisoning and procedural complications Fall	0.00% 0/4 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Psychiatric disorders Confusion	0.00% 0/4 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Nervous system disorders Freezing of Gait	25.0% 1/4 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/10 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Gastrointestinal disorders Diarrhea	25.0% 1/4 • Number of events 2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	20.0% 2/10 • Number of events 2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	50.0% 1/2 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Psychiatric disorders Hallucinations	25.0% 1/4 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/10 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Nervous system disorders Headache	25.0% 1/4 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Gastrointestinal disorders Heartburn	25.0% 1/4 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	30.0% 3/10 • Number of events 3 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Metabolism and nutrition disorders Lightheadedness	50.0% 2/4 • Number of events 2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	40.0% 4/10 • Number of events 7 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
General disorders Low energy	25.0% 1/4 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/10 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Metabolism and nutrition disorders Low glucose	25.0% 1/4 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/10 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Injury, poisoning and procedural complications Discomfort in Scanner	25.0% 1/4 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
General disorders Sleep changes	25.0% 1/4 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/10 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Musculoskeletal and connective tissue disorders Muscle soreness	0.00% 0/4 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
Gastrointestinal disorders Stomach ache	0.00% 0/4 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.
General disorders Throat irritation	0.00% 0/4 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	10.0% 1/10 • Number of events 1 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.	0.00% 0/2 • For all subjects, data was collected during the 30 +/- 7 days of tributyrin intervention.