Lewy Body Dementia, Parkinson Disease, Parkinson Disease Dementia
Conditions
Keywords
ketone ester, ketosis, functional neuroimaging
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.
Interventions
DIETARY_SUPPLEMENTKetone Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate
Ketone ester (KE) dietary supplement (KetoneAid)
Sponsors
Farmer Family Foundation
University of Michigan
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Metabolism | Pre and post approximately 30 days of intervention | 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. |
| Clinical Dementia Rating Scale Score | Pre and post approximately 30 days of intervention | 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. |
Countries
United States
Participant flow
Pre-assignment details
16 participants were enrolled in the study. There were no withdrawals.
Participants by arm
| Arm | Count |
|---|---|
| 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) | 4 |
| 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) | 10 |
| 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) | 2 |
| Total | 16 |
Baseline characteristics
| Characteristic | Parkinson Disease | Parkinson Disease Dementia/Lewy Body Dementia | Healthy Controls | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 10 Participants | 2 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 77 years STANDARD_DEVIATION 4.03 | 74.5 years STANDARD_DEVIATION 4.93 | 70 years STANDARD_DEVIATION 1.41 | 74.63 years STANDARD_DEVIATION 4.76 |
| Education | 19.0 years STANDARD_DEVIATION 3.56 | 16.7 years STANDARD_DEVIATION 4.52 | 17.0 years STANDARD_DEVIATION 1.41 | 17.31 years STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 10 Participants | 2 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Modified Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRSIII) | 46.00 units on a scale STANDARD_DEVIATION 5.9 | 47.80 units on a scale STANDARD_DEVIATION 11.22 | 6.75 units on a scale STANDARD_DEVIATION 9.55 | 44.23 units on a scale STANDARD_DEVIATION 16.76 |
| Montreal Cognitive Assessment (MoCA) | 22.25 units on a scale STANDARD_DEVIATION 4.27 | 17.00 units on a scale STANDARD_DEVIATION 7.41 | 24.00 units on a scale STANDARD_DEVIATION 1.41 | 19.19 units on a scale STANDARD_DEVIATION 6.75 |
| Parkinson's Disease Cognitive Rating Scale (PDCRS) | 66.75 units on a scale STANDARD_DEVIATION 16.13 | 48.50 units on a scale STANDARD_DEVIATION 25.31 | 79.00 units on a scale STANDARD_DEVIATION 7.07 | 56.88 units on a scale STANDARD_DEVIATION 24.04 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 10 Participants | 2 Participants | 16 Participants |
| Region of Enrollment United States | 4 participants | 10 participants | 2 participants | 16 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 10 Participants | 2 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 10 | 0 / 2 |
| other Total, other adverse events | 4 / 4 | 8 / 10 | 1 / 2 |
| serious Total, serious adverse events | 0 / 4 | 0 / 10 | 0 / 2 |
Outcome results
Primary
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). 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Parkinson Disease | Clinical Dementia Rating Scale Score | Pre-intervention | 0.5 score on a scale | Standard Deviation 0.41 |
| Parkinson Disease | Clinical Dementia Rating Scale Score | Post-intervention | 0.5 score on a scale | Standard Deviation 0.41 |
| Parkinson Disease Dementia/Lewy Body Dementia | Clinical Dementia Rating Scale Score | Pre-intervention | 1.0 score on a scale | Standard Deviation 0.85 |
| Parkinson Disease Dementia/Lewy Body Dementia | Clinical Dementia Rating Scale Score | Post-intervention | 1.15 score on a scale | Standard Deviation 0.88 |
| Healthy Controls | Clinical Dementia Rating Scale Score | Pre-intervention | 0 score on a scale | Standard Deviation 0 |
| Healthy Controls | Clinical Dementia Rating Scale Score | Post-intervention | 0.25 score on a scale | Standard Deviation 0.35 |
p-value: 0.37Wilcoxon (Mann-Whitney)
Primary
Glucose Metabolism
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Parkinson Disease | Glucose Metabolism | Pre-intervention | 133.0 milligrams per deciliter (mg/dL) | Standard Deviation 20.3 |
| Parkinson Disease | Glucose Metabolism | Post-intervention | 128.25 milligrams per deciliter (mg/dL) | Standard Deviation 18.26 |
| Parkinson Disease Dementia/Lewy Body Dementia | Glucose Metabolism | Pre-intervention | 134.86 milligrams per deciliter (mg/dL) | Standard Deviation 24.3 |
| Parkinson Disease Dementia/Lewy Body Dementia | Glucose Metabolism | Post-intervention | 132.86 milligrams per deciliter (mg/dL) | Standard Deviation 33.42 |
| Healthy Controls | Glucose Metabolism | Pre-intervention | 179.50 milligrams per deciliter (mg/dL) | Standard Deviation 19.09 |
| Healthy Controls | Glucose Metabolism | Post-intervention | 170.50 milligrams per deciliter (mg/dL) | Standard Deviation 21.92 |
p-value: 0.875Wilcoxon (Mann-Whitney)
p-value: 0.73995% CI: [-16.026, 12.026]t-test, 2 sided