Back to resultsBrain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones
Primary Purpose
Parkinson Disease, Lewy Body Dementia, Parkinson Disease Dementia
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease focused on measuring ketone ester, ketosis, functional neuroimaging
Eligibility Criteria
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
Sites / Locations
- Domino's FarmsRecruiting
- University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Parkinson Disease
Parkinson Disease Dementia/Lewy Body Dementia
Healthy Controls
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain
Brain PET glucose radiotracer binding ratio relative to reference region
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).
Secondary Outcome Measures
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.
Montreal Cognitive Assessment (MoCA) score
Cognitive rating scale for early detection of mild cognitive impairment (Scoring: 0-30, with higher scores indicating better performance).
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.
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.
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.
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.
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).
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).
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).
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.
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.
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.
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).
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).
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.
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).
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.
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.
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.
Full Information
NCT ID
NCT05778695
First Posted
February 21, 2023
Last Updated
April 24, 2023
Sponsor
University of Michigan
Collaborators
Farmer Family Foundation
1. Study Identification
Unique Protocol Identification Number
NCT05778695
Brief Title
Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones
Official Title
Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 9, 2023 (Actual)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
May 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
Farmer Family Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease, Lewy Body Dementia, Parkinson Disease Dementia
Keywords
ketone ester, ketosis, functional neuroimaging
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Parkinson Disease
Arm Type
Experimental
Arm Description
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.
Arm Title
Parkinson Disease Dementia/Lewy Body Dementia
Arm Type
Experimental
Arm Description
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.
Arm Title
Healthy Controls
Arm Type
Experimental
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Ketone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate
Other Intervention Name(s)
KetoneAid
Intervention Description
Ketone ester (KE) dietary supplement (KetoneAid)
Primary Outcome Measure Information:
Title
Average Glucose metabolism
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain
Description
Brain PET glucose radiotracer binding ratio relative to reference region
Time Frame
after approximately 30 days of intervention
Title
Clinical Dementia Rating scale score
Description
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).
Time Frame
after approximately 30 days of intervention
Secondary Outcome Measure Information:
Title
Root mean square of center of pressure (COP) during the instrumented Sway test (iSWAY) eyes open condition
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Montreal Cognitive Assessment (MoCA) score
Description
Cognitive rating scale for early detection of mild cognitive impairment (Scoring: 0-30, with higher scores indicating better performance).
Time Frame
after approximately 30 days of intervention
Title
Time to complete the Instrumented Timed Up and Go test (iTUG)
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Mini Balance Evaluation Systems test (Mini-BESTest) Score
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Average gait speed
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Number of correct responses on the Wechsler Adult Intelligence Scale III (WAIS-III) Digit Symbol Coding test
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Percentage of participants with increased scores on Parkinson's Disease (PD)-Cognitive Rating Scale
Description
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).
Time Frame
after approximately 30 days of intervention
Title
Change in scores on the Boston Naming Test
Description
30-item test to examine confrontational word retrieval (Scoring: 0-30, a higher score indicates better performance).
Time Frame
after approximately 30 days of intervention
Title
Change in scores on the California Verbal Learning Test-II (CVLT-II) of verbal learning and memory
Description
Assessment of verbal learning and memory (Scoring: 0-16, a higher score indicates better performance).
Time Frame
after approximately 30 days of intervention
Title
Time to complete Stroop Color Word Interference Test
Description
During this test, participants read congruent and incongruent colored names of colors. Better performance is indicated by lower time to complete in seconds.
Time Frame
after approximately 30 days of intervention
Title
Time taken to complete the Delis-Kaplan Executive Function System (DKEFS) Trail Making Test
Description
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.
Time Frame
after approximately 30 days of intervention
Title
DKEFS Sorting Test combined score
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Number of correct responses on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Digit Span test
Description
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).
Time Frame
after approximately 30 days of intervention
Title
Number of correct responses on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Matrix Reasoning test
Description
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).
Time Frame
after approximately 30 days of intervention
Title
Number of correct responses on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Digit Backwards
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Number of correct responses on the Wechsler Adult Intelligence Scale IV (WAIS-IV) Information test
Description
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).
Time Frame
after approximately 30 days of intervention
Title
Change in Benton Judgement of Line Orientation scores
Description
This 30-item test is a measure of spatial perception, with scores ranging from 0-30. Higher scores indicate better spatial perception.
Time Frame
after approximately 30 days of intervention
Title
Number of words named on the Controlled Oral Word Association or "FAS" test.
Description
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.
Time Frame
after approximately 30 days of intervention
Title
Mean reaction time on reaction time test
Description
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.
Time Frame
after approximately 30 days of intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexis Griggs, BA
Phone
734-998-8420
Email
gralexis@med.umich.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Jeff Bohnen, BSc
Phone
734-998-8400
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolaas Bohnen, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Domino's Farms
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexis Griggs, BA
Phone
734-998-8420
Email
gralexis@med.umich.edu
Facility Name
University Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexis Griggs, BA
Phone
734-998-8420
Email
gralexis@med.umich.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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Brain Small Chain Fatty Acid Metabolism in Parkinson Disease: Ketones
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