Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones

Small exploratory open-label pilot study to assess supplementation of a ketone ester (KetoneAid) as a potential therapy for persons with Parkinson disease (PD), Parkinson Disease Dementia/Lewy Body Dementia (PDD/LBD), and healthy controls.

Study Overview

• Status: Terminated
• Conditions: Parkinson Disease; Lewy Body Dementia; Parkinson Disease Dementia
• Intervention / Treatment: Dietary supplement: Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate

Detailed Description

The overarching goal of this study is to investigate glucose metabolic, cognitive, clinical and imaging changes in persons with PD and PDD/LBD before and after a month supplementation of a ketone ester (KetoneAid) in a small open label exploratory clinical trial. Positive findings in this small exploratory pilot trial may support future target engagement studies of ketone supplementation in PD and normal adults.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jeff Bohnen, BSc; Phone Number: 734-998-8400
• Study Contact Backup: Name: Alexis Griggs, BA; Phone Number: 734-998-8420; Email: gralexis@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University Hospital
      • Contact: Alexis Griggs, BA; Phone Number: 734-998-8420; Email: gralexis@med.umich.edu
    • Ann Arbor, Michigan, United States, 48105
      • Domino's Farms
      • Contact: Alexis Griggs, BA; Phone Number: 734-998-8420; Email: gralexis@med.umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 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
• People with Parkinson's Disease Dementia or Lewy Body Dementia over 45 years of age

Exclusion Criteria:

• Participants 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, high dose (>100mg QD) of quetiapine, or neuroleptic drugs
• History of significant GI disease
• Significant metabolic or uncontrolled medical comorbidity
• Poorly controlled diabetes
• Pregnancy or breast feeding
• Current excessive alcohol use
• Suicidal ideation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Dietary supplement: Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate; Ketone ester (KE) dietary supplement (KetoneAid); Other Names: KetoneAid
Experimental: 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.	Dietary supplement: Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate; Ketone ester (KE) dietary supplement (KetoneAid); Other Names: KetoneAid
Experimental: 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.	Dietary supplement: Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate; Ketone ester (KE) dietary supplement (KetoneAid); Other Names: KetoneAid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Glucose metabolism	7-10 day average glucose metabolism measured via continuous glucose monitor. Average glucose metabolism will be compared pre and post intervention with the Ketone Ester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate.	after approximately 30 days of intervention
Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain	Brain PET glucose radiotracer binding ratio relative to reference region	after approximately 30 days of intervention
Clinical Dementia Rating scale score	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).	after approximately 30 days of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Root mean square of center of pressure (COP) during the instrumented Sway test (iSWAY) eyes open condition	Root mean square of COP is a measure of postural sway collected during the eyes open condition of the iSWAY test in which participants stand on a firm surface with their eyes open and arms crossed over their chest for 30 seconds.	after approximately 30 days of intervention
Montreal Cognitive Assessment (MoCA) score	Cognitive rating scale for early detection of mild cognitive impairment (Scoring: 0-30, with higher scores indicating better performance).	after approximately 30 days of intervention
Time to complete the Instrumented Timed Up and Go test (iTUG)	Mobility test that evaluates the amount of time it takes the participants to stand, walk 10 feet, turn around, walk, and sit back down. Improved performance is indicated by lower time to complete measured in seconds.	after approximately 30 days of intervention
Mini Balance Evaluation Systems test (Mini-BESTest) Score	The Mini-BESTest is a 14 item scale used to measure different balance control systems: 1) Anticipatory, 2) Reactive Postural Control, 3) Sensory Orientation, 4) Dynamic Gait. This will be used to compare scores from pre and post intervention visits, with scores ranging from 0-28, higher scores indicating better performance.	after approximately 30 days of intervention
Average gait speed	Gait speed (m/s) as measured by the Protokinetics Zeno™ Walkway, which detects pressure as participants walk across it and can be used to determine gait speed.	after approximately 30 days of intervention
Number of correct responses on the Wechsler Adult Intelligence Scale III (WAIS-III) Digit Symbol Coding test	Participants will use a key consisting of numbers and symbols to complete a pattern in a given amount of time. Better performance on the test is indicated by greater number of correct, written symbols in a given amount of time.	after approximately 30 days of intervention
Percentage of participants with increased scores on Parkinson's Disease (PD)-Cognitive Rating Scale	Cognitive scale designed to capture impairments in cognitive function in Parkinson's disease. (Scoring: 0-134, with higher scores indicating better performance). Scores from before and after the intervention will be compared to determine the percentage of participants who see an improvement (indicated by ≥ 4-point higher score).	after approximately 30 days of intervention
Change in scores on the Boston Naming Test	30-item test to examine confrontational word retrieval (Scoring: 0-30, a higher score indicates better performance).	after approximately 30 days of intervention
Change in scores on the California Verbal Learning Test-II (CVLT-II) of verbal learning and memory	Assessment of verbal learning and memory (Scoring: 0-16, a higher score indicates better performance).	after approximately 30 days of intervention
Time to complete Stroop Color Word Interference Test	During this test, participants read congruent and incongruent colored names of colors. Better performance is indicated by lower time to complete in seconds.	after approximately 30 days of intervention
Time taken to complete the Delis-Kaplan Executive Function System (DKEFS) Trail Making Test	Participants complete five conditions where they must draw a trail from different numbers and letters based on the instructions. Each condition is timed. Mean time to complete will be compare from pre and post intervention visits to determine the effect of the supplement on processing speed and visual attention. Better performance is indicated by lower completion time in seconds.	after approximately 30 days of intervention
DKEFS Sorting Test combined score	Participants are given a set of cards that are different shapes, colors, sizes, and have different words printed on them. Participants sort these cards into as many groups as possible in 4 minutes or up to 10 sorts. They are then given presorted groups and must identify what they are sorted by. Both tasks are performed twice. Each task is scored from 0-32 for a total possible score out of 128, with higher scores indicating better performance.	after approximately 30 days of intervention
Number of correct responses on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Digit Span test	Participants sequentially order the numbers presented by the examiner. This will be used to compare the number of correct responses given at pre and post intervention visits to quantify if information processing speed improves (indicated by increased number of correct responses).	after approximately 30 days of intervention
Number of correct responses on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Matrix Reasoning test	This is a nonverbal reasoning task in which individuals are asked to identify patterns in designs which measures perceptual organization and nonverbal reasoning (Scoring: 0-16, with higher scores indicating better performance).	after approximately 30 days of intervention
Number of correct responses on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Digit Backwards	Participants are read a sequence of numbers and asked to repeat the same sequence back to the examiner in reverse order. (Scoring: 0-16, with higher scores indicating better performance). Number of correct responses given at pre and post intervention visits will be compared.	after approximately 30 days of intervention
Number of correct responses on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Information test	This test consists of 26 questions aimed at determining how much general knowledge the participant has accumulated from their environment (Scoring: 0-26, with higher scores indicating better performance).	after approximately 30 days of intervention
Change in Benton Judgement of Line Orientation scores	This 30-item test is a measure of spatial perception, with scores ranging from 0-30. Higher scores indicate better spatial perception.	after approximately 30 days of intervention
Number of words named on the Controlled Oral Word Association or "FAS" test.	The participants produce as many words as they can that begin with the given letter (F, A, or S) within a 1-min time period. Greater number of words produced indicates better performance on the test.	after approximately 30 days of intervention
Mean reaction time on reaction time test	Participants are shown an arrow pointing left or right on a screen and must click a button on a controller corresponding to the correct direction as quickly as possible. How quickly participants press the button is their reaction time, which is measured in milliseconds.	after approximately 30 days of intervention

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Farmer Family Foundation
• Investigators: Principal Investigator: Nicolaas Bohnen, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2023
• Primary Completion (Actual): October 4, 2023
• Study Completion (Actual): October 4, 2023

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: March 9, 2023
• First Posted (Actual): March 21, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: functional neuroimaging; ketosis; ketone ester
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Dementia; Lewy Body Disease
• Other Study ID Numbers: HUM00213035

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: No
• Studies a U.S. FDA-regulated device product: No