Exogenous Ketones in Type 2 Diabetes
Primary Purpose
Ketosis, Type 2 Diabetes
Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Ketone monoester
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Ketosis
Eligibility Criteria
Inclusion Criteria:
- physician-diagnosed type 2 diabetes of ≥1 year
- current hemoglobin A1C (HbA1c) of 6.5-8.0%
- treatment with lifestyle or stable (≥3 months) oral glucose-lowering medications
- blood pressure of <160/99 mm Hg assessed according to guidelines
- non-smoking
- no prior history of cardiovascular disease or stroke
- not on hormone replacement therapy, corticosteroids, or anti-inflammatory medications
- 20-75 years old
Exclusion Criteria:
- being a competitive endurance athlete
- taking exogenous insulin or sodium glucose transporter 2 (SGLT2) inhibitors
- following a ketogenic diet, low-calorie diet, periodic fasting regimen, or consume ketogenic supplements
- being unable to travel to and from the university
- being unable to follow the controlled diet instructions
- being pregnant or planning to become pregnant during the study (if female)
- disorders of fat metabolism, chronic pancreatitis, had gastric bypass surgery and/or gallbladder disease
- being unable to read or communicate in English
Sites / Locations
- University of British Columbia, Okanagan
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ketone monoester
Placebo
Arm Description
Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight)
Acute dose of flavour-matched placebo.
Outcomes
Primary Outcome Measures
Plasma glucose
Plasma glucose concentration after ketone or placebo ingestion
Secondary Outcome Measures
Plasma insulin
Insulin across concentration after ketone or placebo ingestion
Plasma C-peptide
C-peptide across concentration after ketone or placebo ingestion
Plasma free fatty acids
Non-esterified fatty acid concentration after ketone or placebo ingestion
Plasma tumour necrosis factor alpha
Plasma tumour necrosis factor alpha concentration after ketone or placebo ingestion
Plasma tumour interleukin-1beta
Plasma tumour interleukin-1beta concentration after ketone or placebo ingestion
Plasma tumour interleukin-6
Plasma tumour interleukin-6 concentration after ketone or placebo ingestion
Cerebral blood flow
Intracranial blood flow velocity measured by ultrasound
Blood pressure
Blood pressure measured manually and by Finipres
Cognitive function
Measures of cognitive function using Brain Baseline battery on an iPad.
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor concentrations after ketone or placebo ingestion
Blood monocytes
Total blood monocytes and monocyte subsets after ketone or placebo ingestion
Self reported hunger and fullness
Self reported hunger and fullness by a 0 to 100 mm Visual Analog Scale (higher scores mean greater hunger or fullness)
Gastrointestinal symptoms
Gastroinestinal symptom questionnaire scores after ketone or placebo ingestion on a 0 to 100 mm Visual Analog Scale (higher scores mean greater symptoms)
Total energy consumed
Total energy consumed in kilocalories in buffet style meal after ketone or placebo ingestion
Monocyte histone acetylation
Histone acetylation status of monocytes measured after ketone or placebo ingestion
Full Information
NCT ID
NCT04194450
First Posted
December 9, 2019
Last Updated
July 29, 2022
Sponsor
University of British Columbia
1. Study Identification
Unique Protocol Identification Number
NCT04194450
Brief Title
Exogenous Ketones in Type 2 Diabetes
Official Title
The Effect of Acute Exogenous Oral Ketone Supplementation on Blood Glucose Levels in Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
January 15, 2020 (Actual)
Primary Completion Date
May 20, 2022 (Actual)
Study Completion Date
May 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Exogenous ketone supplements are proposed to have glucose-lowering potential, provide an alternative fuel for the brain and to enhance cognitive function. No studies have tested whether exogenous ketones can lower blood glucose in people with type 2 diabetes. In addition, the impact of exogenous ketones on brain blood flow, cognitive function or brain-derived neurotrophic factor in humans is unknown. The purpose of this study is to determine if acutely ingesting exogenous ketones, in the form of a ketone monoester drink, can lower glucose and improve measures of brain/cognitive function in humans with type 2 diabetes. Participants will consume a ketone monoester drink or placebo with blood samples, brain blood flow, and cognitive function assessed over 180 minutes. The researchers will also test how the ketone monoester drink impacts appetite and measures of inflammation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ketosis, Type 2 Diabetes
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Placebo masked with flavouring and participants consume in opaque containers.
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ketone monoester
Arm Type
Experimental
Arm Description
Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Acute dose of flavour-matched placebo.
Intervention Type
Dietary Supplement
Intervention Name(s)
Ketone monoester
Intervention Description
Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Primary Outcome Measure Information:
Title
Plasma glucose
Description
Plasma glucose concentration after ketone or placebo ingestion
Time Frame
180 minutes
Secondary Outcome Measure Information:
Title
Plasma insulin
Description
Insulin across concentration after ketone or placebo ingestion
Time Frame
180 minutes
Title
Plasma C-peptide
Description
C-peptide across concentration after ketone or placebo ingestion
Time Frame
180 minutes
Title
Plasma free fatty acids
Description
Non-esterified fatty acid concentration after ketone or placebo ingestion
Time Frame
180 minutes
Title
Plasma tumour necrosis factor alpha
Description
Plasma tumour necrosis factor alpha concentration after ketone or placebo ingestion
Time Frame
180 minutes
Title
Plasma tumour interleukin-1beta
Description
Plasma tumour interleukin-1beta concentration after ketone or placebo ingestion
Time Frame
180 minutes
Title
Plasma tumour interleukin-6
Description
Plasma tumour interleukin-6 concentration after ketone or placebo ingestion
Time Frame
180 minutes
Title
Cerebral blood flow
Description
Intracranial blood flow velocity measured by ultrasound
Time Frame
180 minutes
Title
Blood pressure
Description
Blood pressure measured manually and by Finipres
Time Frame
180 minutes
Title
Cognitive function
Description
Measures of cognitive function using Brain Baseline battery on an iPad.
Time Frame
180 minutes
Title
Brain-derived neurotrophic factor
Description
Brain-derived neurotrophic factor concentrations after ketone or placebo ingestion
Time Frame
180 minutes
Title
Blood monocytes
Description
Total blood monocytes and monocyte subsets after ketone or placebo ingestion
Time Frame
180 minutes
Title
Self reported hunger and fullness
Description
Self reported hunger and fullness by a 0 to 100 mm Visual Analog Scale (higher scores mean greater hunger or fullness)
Time Frame
180 minutes
Title
Gastrointestinal symptoms
Description
Gastroinestinal symptom questionnaire scores after ketone or placebo ingestion on a 0 to 100 mm Visual Analog Scale (higher scores mean greater symptoms)
Time Frame
180 minutes
Title
Total energy consumed
Description
Total energy consumed in kilocalories in buffet style meal after ketone or placebo ingestion
Time Frame
180 minutes after ketone or placebo ingestion
Title
Monocyte histone acetylation
Description
Histone acetylation status of monocytes measured after ketone or placebo ingestion
Time Frame
180 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
physician-diagnosed type 2 diabetes of ≥1 year
current hemoglobin A1C (HbA1c) of 6.5-8.0%
treatment with lifestyle or stable (≥3 months) oral glucose-lowering medications
blood pressure of <160/99 mm Hg assessed according to guidelines
non-smoking
no prior history of cardiovascular disease or stroke
not on hormone replacement therapy, corticosteroids, or anti-inflammatory medications
20-75 years old
Exclusion Criteria:
being a competitive endurance athlete
taking exogenous insulin or sodium glucose transporter 2 (SGLT2) inhibitors
following a ketogenic diet, low-calorie diet, periodic fasting regimen, or consume ketogenic supplements
being unable to travel to and from the university
being unable to follow the controlled diet instructions
being pregnant or planning to become pregnant during the study (if female)
disorders of fat metabolism, chronic pancreatitis, had gastric bypass surgery and/or gallbladder disease
being unable to read or communicate in English
Facility Information:
Facility Name
University of British Columbia, Okanagan
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1V 1V7
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Exogenous Ketones in Type 2 Diabetes
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