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Ketone bodies are a fuel source and signaling molecule that are produced by your body during prolonged fasting or if you consistently eat at low-carbohydrate diet. Blood ketones can be used as a source of energy during fasting and are used by your brain as an alternative source of fuel to glucose. Previous studies have found that ketones, when consumed in form of a supplement drink, can increase blood ketone levels and lower blood glucose, the amount of sugar in your blood. This is of potential interest for individuals with high blood sugar, such as people living with type 2 diabetes. However, there are different types of ketone supplements that differ in how they are metabolized in the body. Little is known about how these supplements affect blood ketone and blood glucose levels. The main objective of this study is to determine the effect of three different ketone supplements on blood ketones and blood glucose. The results of this pilot study will be used to guide future research for larger and more extensive studies on ketone supplements.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester | Active Comparator | 1 x 20 mL |
|
| Beta-hydroxybutyric acid | Experimental | 1 x 237 mL |
|
| 1,3-Butanediol | Experimental | 1 x 35 mL |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester | Dietary Supplement | Single-dose pharmacokinetic study over 4 hours. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Blood Beta-hydroxybutyrate | Are under the curve (AUC) across 240 minutes after supplement consumption (assessed at baseline and 15, 30, 60, 90, 120, 180, and 240 post-supplementation) | 240 minutes (assessed at baseline and 15, 30, 60, 90, 120, 180, 240 minutes post-supplementation) |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Glucose | Area under the curve (AUC) | 240 minutes (assessed at baseline and 15, 30, 60, 90, 120, 180, 240 minutes post-supplementation) |
| Blood Pressure | Change over time |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of British Columbia Okanagan | Kelowna | British Columbia | V1V 1V7 | Canada |
The investigators will share individual patient data (de-identified) with researchers upon request.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 | 1 x 20 mL; (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester; single-dose pharmacokinetic study over 4 hours. 1 x 237 mL; Beta-hydroxybutyric acid; single-dose pharmacokinetic study over 4 hours. 1 x 35 mL; 1,3-Butanediol; single-dose pharmacokinetic study over 4 hours. |
| FG001 | Arm 2 | 1 x 20 mL; (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester; single-dose pharmacokinetic study over 4 hours. 1 x 35 mL; 1,3-Butanediol; single-dose pharmacokinetic study over 4 hours. 1 x 237 mL; Beta-hydroxybutyric acid; single-dose pharmacokinetic study over 4 hours. |
| FG002 | Arm 3 | 1 x 35 mL; 1,3-Butanediol; single-dose pharmacokinetic study over 4 hours. 1 x 237 mL; Beta-hydroxybutyric acid; single-dose pharmacokinetic study over 4 hours. 1 x 20 mL; (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester; single-dose pharmacokinetic study over 4 hours. |
| FG003 | Arm 4 | 1 x 35 mL; 1,3-Butanediol; single-dose pharmacokinetic study over 4 hours. 1 x 20 mL; (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester; single-dose pharmacokinetic study over 4 hours. 1 x 237 mL; Beta-hydroxybutyric acid; single-dose pharmacokinetic study over 4 hours. |
| FG004 | Arm 5 | 1 x 237 mL; Beta-hydroxybutyric acid; single-dose pharmacokinetic study over 4 hours. 1 x 35 mL; 1,3-Butanediol; single-dose pharmacokinetic study over 4 hours. 1 x 20 mL; (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester; single-dose pharmacokinetic study over 4 hours. |
| FG005 | Arm 6 | 1 x 237 mL; Beta-hydroxybutyric acid; single-dose pharmacokinetic study over 4 hours. 1 x 20 mL; (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester; single-dose pharmacokinetic study over 4 hours. 1 x 35 mL; 1,3-Butanediol; single-dose pharmacokinetic study over 4 hours. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention Period 1 |
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| Intervention Period 2 |
| |||||||||||||
| Intervention Period 3 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Single-dose pharmacokinetic study over 4 hours, three-way crossover study of three different ketone supplements (see description). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Blood Beta-hydroxybutyrate | Are under the curve (AUC) across 240 minutes after supplement consumption (assessed at baseline and 15, 30, 60, 90, 120, 180, and 240 post-supplementation) | Posted | Mean | Standard Deviation | area under the curve (mmol/L x 240 min) | 240 minutes (assessed at baseline and 15, 30, 60, 90, 120, 180, 240 minutes post-supplementation) |
|
Over the course of the three acute in-laboratory testing days
Adverse events were any events reported or experienced by participants. We did not assess all-cause mortality as this was an acute one-day study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | (R)-3-hydroxybutyl (R)-3-hydroxybutyrate Ketone Monoester | 1 x 20 mL (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester: Single-dose pharmacokinetic study over 4 hours. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan Little, PhD | University of British Columbia | 2508079876 | jonathan.little@ubc.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 15, 2022 | Dec 22, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007662 | Ketosis |
| ID | Term |
|---|---|
| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D020155 | 3-Hydroxybutyric Acid |
| C028491 | 1,3-butylene glycol |
| ID | Term |
|---|---|
| D006885 | Hydroxybutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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|
| Beta-hydroxybutyric acid | Dietary Supplement | Beta-hydroxybutyric acid |
|
|
| 1,3-Butanediol | Dietary Supplement | 1,3-Butanediol |
|
|
| 240 minutes (assessed at baseline and 15, 30, 60, 90, 120, 180, 240 minutes post-supplementation) |
| Heart Rate | Change over time | 240 minutes (assessed at baseline and 15, 30, 60, 90, 120, 180, 240 minutes post-supplementation) |
| Supplement Acceptability & Taste | Questionnaire | 240 minutes post-supplementation |
| Hunger & Fullness | Questionnaire | 240 minutes post-supplementation |
| Gastrointestinal Discomfort | Questionnaire | 60 minutes post-supplementation |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | 1,3-Butanediol | 1 x 35 mL 1,3-Butanediol: 1,3-Butanediol |
|
|
| Secondary | Blood Glucose | Area under the curve (AUC) | Not Posted | 240 minutes (assessed at baseline and 15, 30, 60, 90, 120, 180, 240 minutes post-supplementation) | Participants |
| Secondary | Blood Pressure | Change over time | Not Posted | 240 minutes (assessed at baseline and 15, 30, 60, 90, 120, 180, 240 minutes post-supplementation) | Participants |
| Secondary | Heart Rate | Change over time | Not Posted | 240 minutes (assessed at baseline and 15, 30, 60, 90, 120, 180, 240 minutes post-supplementation) | Participants |
| Secondary | Supplement Acceptability & Taste | Questionnaire | Not Posted | 240 minutes post-supplementation | Participants |
| Secondary | Hunger & Fullness | Questionnaire | Not Posted | 240 minutes post-supplementation | Participants |
| Secondary | Gastrointestinal Discomfort | Questionnaire | Not Posted | 60 minutes post-supplementation | Participants |
| 0 |
| 0 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Beta-hydroxybutyric Acid | 1 x 237 mL Beta-hydroxybutyric acid: Beta-hydroxybutyric acid | 0 | 0 | 0 | 12 | 0 | 12 |
| EG002 | 1,3-Butanediol | 1 x 35 mL 1,3-Butanediol: 1,3-Butanediol | 0 | 0 | 0 | 12 | 0 | 12 |
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| D009930 |
| Organic Chemicals |
| D006880 | Hydroxy Acids |
| D007657 | Ketone Bodies |
| D007659 | Ketones |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |