Diabetes Mellitus, Type 2NCT05155410
Examining the Effect of Exogenous Ketone Supplementation on Glucose Control in Type 2 Diabetes
A study testing Exogenous Ketone Monoester in people with Diabetes Mellitus, Type 2, run by University of British Columbia at 1 site in Canada.
Trial summary
Ketone bodies are a fuel source and signaling molecule that are produced by the body during prolonged fasting or if an individuals consistently eats a low-carbohydrate "keto" diet. Read more about this study
- Who is it for?
- Ages 30 to 69 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Exogenous Ketone Monoester
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 15 Feb 2022to 3 Feb 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a type 2 diabetes diagnosis from a physician
- Have stable use of glucose-lowering medications for at least 3 months
Who cannot join
- Are a competitively trained endurance athlete
- Are actively attempting to gain or lose weight
- Have a history of mental illness or existing neurological disease(s), cardiovascular events (i.e., heart attack, stroke) in the last 2 years
- Have hypoglycemia, irritable bowel syndrome or inflammatory bowel disease
- Are currently using insulin or SGLT2 inhibitors
- Are using more than 2 classes of glucose-lowering medication
Show all 9Show fewer
- Are currently following a ketogenic diet or taking ketone supplements
- Are unable to commit for a 29-day trial
- Are unable to follow a controlled diet
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of British Columbia Okanagan
Kelowna, British Columbia, V1V 3G1
About this study
Official title: Effect of 14 Days of Exogenous Ketone Supplementation on Glycemic Control in Type 2 Diabetes: a Randomized Placebo-controlled Crossover Trial
Ketone bodies are a fuel source and signaling molecule that are produced by the body during prolonged fasting or if an individuals consistently eats a low-carbohydrate "keto" diet. Blood ketones can be used as a source of energy by the body, but they may also act as signals that impact the functioning of different cells in the body. Recently, the availability of ketone supplements that can be taken orally allows for raising blood ketones without having to fast or eat a "keto" diet. The investigators' studies and those of other researchers have shown that ketone supplementation can lower blood sugar without having to make any other dietary changes. Oral ingestion of ketones may therefore be an effective strategy to improve blood sugar control and influence how cells function.
The main objective of this study is to determine if consuming a ketone supplement 3 times per day (before meals) for 14 days lowers blood sugar and impacts how the body's cells function. The results of this study will be used to guide future recommendations on the utility of ketone supplements for improving health in individuals with, or at elevated risk of, type 2 diabetes.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Exogenous Ketone Monoester, Placebo
- Keywords
- 3-Hydroxybutyric Acid, Glycemic Control, Hyperglycemia, Ketones, Glucose Control, Inflammation, Immune cell function, Cognition
- Medical subject headings
- Diabetes Mellitus, Type 2, Hyperglycemia, Ketosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exogenous Ketone MonoesterDietary supplement
Also called KetoneAid KE4 Ketone Ester, D-β-hydroxybutyrate-R 1,3-Butanediol
Participants will consume 15g of the oral ketone monoester supplement 15 minutes prior to each meal of the day for 14 days. All meals will be provided throughout the 14-day supplementation period.
PlaceboDietary supplement
Also called Flavor- and volume-matched placebo supplement
Participants will consume an equivalent volume (30ml) of the active intervention supplement 15 minutes prior to each meal for 14 days. All meals will be provided throughout the 14-day placebo supplementation period.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Participants will consume 15 g of an active oral exogenous ketone monoester supplement 15 minutes prior to each meal of the day for a 14-day period.
Pre-intervention (baseline) and post-intervention measurements will be obtained before and immediately after the 14-day period.
All meals will be provided throughout the supplementation period Participants will wear a continuous glucose monitor for the first 10 consecutive days during the supplementation period. Receives: Dietary Supplement: Exogenous Ketone Monoester |
| Placebo | Placebo comparator | Participants will consume a flavor-matched placebo drink and undergo the same procedures described in the Experimental Arm Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose Control: Change in Fructosamine
Change in glucose control (from pre-intervention Day 0) will be quantified by serum fructosamine obtained by fasting blood sample in both conditions.
Measured: Day 14 (post-intervention)
Secondary outcomes (27)
Vascular function
Vascular function will be assessed by flow mediated dilation of the brachial artery using vascular ultrasound. A cuff will affixed on the forearm, distal to the brachial artery and will be inflated for 5 minutes. Flow mediation dilation will be measured over a 3-minute period following cuff release.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Cognition: N-back test
Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the computer-based app Inqisit6 Lab (Millisecond). The test will be the n-back test.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Cognition: Digit-symbol substitution test
Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the computer-based app Inquisit6 Lab (Millisecond). The test will be the digit-symbol substitution test.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma insulin at 14 days
Plasma insulin from venous blood samples will be measured using a high-sensitivity human insulin enzyme-like immunosorbent assay (ELISA) run in duplicate.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma free fatty acids at 14 days
Free fatty acids from venous blood samples will be measured by colorimetric assay run in duplicate.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline circulating inflammatory cytokines at 14 days
Key inflammatory cytokines including CRP will be quantified by Mesoscale Discovery U-PLEX run in duplicate.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Phagocytosis
Phagocytosis of fluorescent-labelled E. coli by immune cells from whole blood will be quantified by flow cytometry
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Oxidative Burst
LPS-stimulated oxidative burst by immune cells from whole blood will be quantified by flow cytometry
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Degranulation
Immune cell degranulation will be quantified by enzyme-linked immunosorbent assay run in duplicate (quantifying myeloperoxidase and elastase in whole blood cell culture supernatants).
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Immune Cell Phenotyping
Phenotyping of macrophages and T cells will be quantified by surface and intracellular staining by flow cytometry.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Complete blood count
A 5-part white blood cell differential and complete blood count will be quantified by hematology analyzer.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Glycemic Control: 2hr postprandial hyperglycemia
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing 2hr postprandial hyperglycemia.
Measured: Day 1 through to Day 10
Glycemic Control: 24hr average glucose area under the curve (AUC)
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing 24hr average glucose AUC.
Measured: Day 1 through to Day 10
Glycemic Control: Fasting glucose
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing fasting plasma glucose.
Measured: Day 1 through to Day 10
Glycemic Control: Change in Fasting Plasma glucose
Change in fasting plasma glucose (from pre-intervention Day 0) will be measured by fasting blood sample in both the active and placebo supplement conditions.
Measured: Day 14
Glycemic Control: Glycemic variability
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing glycemic variability.
Measured: Day 1 through to Day 10
Glycemic Control: Time in Target Range
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing time in target range.
Measured: Day 1 through to Day 10
Glycemic Control: HbA1c
Glycemic control will be measured by assessing HbA1c using a point-of-care analyzer.
Measured: Day 0 (pre-intervention) and Day 14 (post-intervention)
Lipid Panel
Lipid panel (total cholesterol, high-density cholesterol, low-density cholesterol, triglycerides, non-HDL cholesterol, cholesterol/HDL ratio) will be measured using a point-of-care analyzer.
Measured: Day 0 (pre-intervention) and Day 14 (post-intervention)
Body weight
Change in body weight will be measured using a body weight scale.
Measured: Day 0 (pre-intervention) and Day 14 (post-intervention)
Blood pressure
Change in blood pressure will be measured using an automated blood pressure device. Both systolic and diastolic blood pressure will be measured.
Measured: Day 0 (pre-intervention) and Day 14 (post-intervention)
Blood beta-hydroxybutyrate
Change in fasting blood beta-hydroxybutyrate will be measured using a standard assay.
Measured: Day 0 (pre-intervention) and Day 14 (post-intervention)
Physical activity
Physical activity will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Measured: Day 0 (pre-intervention) to Day 14 (post-intervention)
Sedentary time
Sedentary time will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Measured: Day 0 (pre-intervention) to Day 14 (post-intervention)
Sleeping time
Sleeping time will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Measured: Day 0 (pre-intervention) to Day 14 (post-intervention)
Resting heart rate
Change resting heart rate will be measured using an automated heart rate monitor device.
Measured: Day 0 (pre-intervention) and Day 14 (post-intervention)
Waist circumference
Change in waist circumference will be measures using a measurement tape.
Measured: Day 0 (pre-intervention) and Day 14 (post-intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2021
- Study start15 Feb 2022
- Primary completion3 Feb 2023
- Study completion3 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonathan Little, University of British Columbia
- Investigators
- Jonathan Little, PhD, Principal investigator, University of British Columbia- Okanagan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05155410
- Sponsor's protocol ID
- H21-01762
- Status last verified
- Apr 2023
- First submitted
- 30 Nov 2021
- Last updated
- 13 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators will share individual patient data (de-identified) with researchers upon reasonable request.
Publications
Baranowski BJ, Oliveira BF, Falkenhain K, Little JP, Mohammad A, Beaudette SM, Finch MS, Caldwell HG, Neudorf H, MacPherson REK, Walsh JJ. Effect of exogenous beta-hydroxybutyrate on BDNF signaling, cognition, and amyloid precursor protein processing in humans with T2D and insulin-resistant rodents. Am J Physiol Cell Physiol. 2025 Feb 1;328(2):C541-C556. doi: 10.1152/ajpcell.00867.2024. Epub 2025 Jan 13.
PubMed 39804761
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of 14 Days of Exogenous Ketone Supplementation on Glycemic Control in Type 2 Diabetes: a Randomized Placebo-controlled Crossover Trial
- ClinicalTrials.gov ID
- NCT05155410
- Acronym / sponsor ID
- H21-01762
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- 3-Hydroxybutyric Acid, Glycemic Control, Hyperglycemia, Ketones, Glucose Control, Inflammation, Immune cell function, Cognition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 15 Feb 2022 (actual)
- Primary completion
- 3 Feb 2023 (actual)
- Study completion
- 3 Feb 2023 (actual)
- First posted
- 13 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ketone bodies are a fuel source and signaling molecule that are produced by the body during prolonged fasting or if an individuals consistently eats a low-carbohydrate "keto" diet. Blood ketones can be used as a source of energy by the body, but they may also act as signals that impact the functioning of different cells in the body. Recently, the availability of ketone supplements that can be taken orally allows for raising blood ketones without having to fast or eat a "keto" diet. The investigators' studies and those of other researchers have shown that ketone supplementation can lower blood sugar without having to make any other dietary changes. Oral ingestion of ketones may therefore be an effective strategy to improve blood sugar control and influence how cells function.
The main objective of this study is to determine if consuming a ketone supplement 3 times per day (before meals) for 14 days lowers blood sugar and impacts how the body's cells function. The results of this study will be used to guide future recommendations on the utility of ketone supplements for improving health in individuals with, or at elevated risk of, type 2 diabetes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Dietary Supplement: Exogenous Ketone MonoesterParticipants will consume 15 g of an active oral exogenous ketone monoester supplement 15 minutes prior to each meal of the day for a 14-day period. Pre-intervention (baseline) and post-intervention measurements will be obtained before and immediately after the 14-day period. All meals will be provided throughout the supplementation period Participants will wear a continuous glucose monitor for the first 10 consecutive days during the supplementation period. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboParticipants will consume a flavor-matched placebo drink and undergo the same procedures described in the Experimental Arm |
Who may qualify
- Ages
- 30 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Have a type 2 diabetes diagnosis from a physician
- Have stable use of glucose-lowering medications for at least 3 months
Key exclusion criteria (9 listed)
- Are a competitively trained endurance athlete
- Are actively attempting to gain or lose weight
- Have a history of mental illness or existing neurological disease(s), cardiovascular events (i.e., heart attack, stroke) in the last 2 years
- Have hypoglycemia, irritable bowel syndrome or inflammatory bowel disease
- Are currently using insulin or SGLT2 inhibitors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exogenous Ketone MonoesterAlso: KetoneAid KE4 Ketone Ester, D-β-hydroxybutyrate-R 1,3-ButanediolParticipants will consume 15g of the oral ketone monoester supplement 15 minutes prior to each meal of the day for 14 days. All meals will be provided throughout the 14-day supplementation period. | Dietary supplement | Experimental |
| PlaceboAlso: Flavor- and volume-matched placebo supplementParticipants will consume an equivalent volume (30ml) of the active intervention supplement 15 minutes prior to each meal for 14 days. All meals will be provided throughout the 14-day placebo supplementation period. | Dietary supplement | Placebo |
Primary outcome
Glucose Control: Change in Fructosamine
Time frame: Day 14 (post-intervention)
Change in glucose control (from pre-intervention Day 0) will be quantified by serum fructosamine obtained by fasting blood sample in both conditions.
27 secondary outcomes
Vascular function
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Cognition: N-back test
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Cognition: Digit-symbol substitution test
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma insulin at 14 days
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma free fatty acids at 14 days
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline circulating inflammatory cytokines at 14 days
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Phagocytosis
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Oxidative Burst
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Degranulation
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Immune Cell Phenotyping
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Complete blood count
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Glycemic Control: 2hr postprandial hyperglycemia
Time frame: Day 1 through to Day 10
Glycemic Control: 24hr average glucose area under the curve (AUC)
Time frame: Day 1 through to Day 10
Glycemic Control: Fasting glucose
Time frame: Day 1 through to Day 10
Glycemic Control: Change in Fasting Plasma glucose
Time frame: Day 14
Glycemic Control: Glycemic variability
Time frame: Day 1 through to Day 10
Glycemic Control: Time in Target Range
Time frame: Day 1 through to Day 10
Glycemic Control: HbA1c
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Lipid Panel
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Body weight
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Blood pressure
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Blood beta-hydroxybutyrate
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Physical activity
Time frame: Day 0 (pre-intervention) to Day 14 (post-intervention)
Sedentary time
Time frame: Day 0 (pre-intervention) to Day 14 (post-intervention)
Sleeping time
Time frame: Day 0 (pre-intervention) to Day 14 (post-intervention)
Resting heart rate
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Waist circumference
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2023.
- Derived from this study: PubMed 39804761Baranowski BJ, Oliveira BF, Falkenhain K, Little JP, Mohammad A, Beaudette SM, Finch MS, Caldwell HG, Neudorf H, MacPherson REK, Walsh JJ. Effect of exogenous beta-hydroxybutyrate on BDNF signaling, cognition, and amyloid precursor protein processing in humans with T2D and insulin-resistant rodents. Am J Physiol Cell Physiol. 2025 Feb 1;328(2):C541-C556. doi: 10.1152/ajpcell.00867.2024. Epub 2025 Jan 13.
- Individual participant dataSharing planned: Yes. The investigators will share individual patient data (de-identified) with researchers upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Little, PhD principal investigator
University of British Columbia- Okanagan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exogenous Ketone Monoester in people with Diabetes Mellitus, Type 2, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucose Control: Change in Fructosamine (time frame: Day 14 (post-intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05155410, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2023.