Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones

Conditions
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Lewy Body Dementia, Parkinson Disease, Parkinson Disease Dementia

Intervention / Treatment
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* Dietary Supplement: Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parkinson Disease<br>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<br>* Ketone ester (KE) dietary supplement (KetoneAid)<br>* Other names: KetoneAid;|
| Experimental: Parkinson Disease Dementia/Lewy Body Dementia<br>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<br>* Ketone ester (KE) dietary supplement (KetoneAid)<br>* Other names: KetoneAid;|
| Experimental: Healthy Controls<br>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<br>* Ketone ester (KE) dietary supplement (KetoneAid)<br>* Other names: KetoneAid;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketone ester, ketosis, functional neuroimaging