Hyperglycemia, PostprandialNCT03817749
Ketone Supplementation, Glucose Control, and Cardiovascular Function
A study testing Exogenous ketone monoester in people with Hyperglycemia, Postprandial and Overweight and Obesity, run by University of British Columbia at 1 site in Canada.
Trial summary
Post-prandial hyperglycemic excursions induce a cascade of deleterious effects on the body, including increased inflammation, production of reactive oxygen species, and impaired cardiovascular function. Ingestion of an exogenous oral ketone supplement blunts hyperglycemia in response to an oral glucose tolerance test. Read more about this study
- Who is it for?
- Ages 30 to 69 years
- Conditions the study is for
- Hyperglycemia, Postprandial, Overweight and Obesity, Diabetes Mellitus Risk
- 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
- 6 Feb 2019to 31 Dec 2020
- 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
- Elevated waist circumference (>102 cm for males, >88 cm for females) and/or Obesity (BMI > 30 kg/m2) and/or Diagnoses of prediabetes based on A1C (5.7-6.4%) and/or fasting plasma glucose (5.6-6.9 mmol/l) using ADA criteria
Who cannot join
- Competitively trained endurance athlete
- Actively attempting to lose weight
- History of mental illness or existing neurological disease(s)
- Previous cardiovascular events (i.e., heart attack, stroke)
- Diagnoses of diabetes
- Hypoglycemia
Show all 10Show fewer
- Irritable bowel syndrome or inflammatory bowel disease
- Taking medication that may interfere with insulin sensitivity
- Currently following a ketogenic diet or taking ketone supplements
- Unable to commit for 2 separate 14-day trials and 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 1V7
About this study
Official title: The Effects of Exogenous Ketone Supplementation on Cardiovascular Function and Glucose Control
Post-prandial hyperglycemic excursions induce a cascade of deleterious effects on the body, including increased inflammation, production of reactive oxygen species, and impaired cardiovascular function. Ingestion of an exogenous oral ketone supplement blunts hyperglycemia in response to an oral glucose tolerance test. Accordingly, it is hypothesized that exogenous ketone supplement ingestion prior to a meal could be an effective strategy for blunting postprandial hyperglycemia. Therefore, the purpose of this study is to investigate the effect of short-term (14-days) pre-meal exogenous ketone supplementation on glucose control, cardiovascular function, inflammation, and oxidative stress in individuals at an elevated risk of type 2 diabetes.
- Being tested
- Exogenous ketone monoester
- Keywords
- Flow mediated dilation, Glucose control, Inflammation, Immune cell function, Cognition, Oxidative stress, Cardiovascular function
- Medical subject headings
- Hyperglycemia, Overweight, Obesity, 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 HVMN ketone monoester supplement
Participants will consume 20g 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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | * Participants will consume 20 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 6 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: Exogenous ketone monoester |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose control
Post-prandial glucose excursions will be measured by continuous glucose monitoring using the iPro2 CGM by Medtronic in both the active and placebo supplement conditions. Post-prandial glucose following breakfast, lunch, and dinner will be averaged together.
Measured: 2 hours after a meal
Secondary outcomes (9)
Change from baseline flow mediated dilation at 14 days
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)
Change from baseline histone acetylation at 14 days
Histone H3 acetylation status will be quantified by flow cytometry using conjugated acetyl-histone H3 antibody specific for Lys9 (Pacific Blue 445) and the conjugated acetyl-histone H3 antibody specific for Lys14 (Alexa Fluor 488).
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline mitochondrial superoxide production at 14 days
Oxidative Stress will be measured by mitochondrial superoxide production in blood lymphocytes, monocytes, and neutrophils by flow cytometry using the MitoSOX red assay (ThermoFisher #M36008) and total intracellular ROS via the DCFDA assay (Sigma #D6883)
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline cognition (executive functions) at 14 days
Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the iPad-based app BrainBaseline. The tests will be the Stroop test, task-switching test, digit-symbol substitution test, and the n-back test.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma glucose at 14 days
Venous blood samples will be taken and plasma glucose will be measured using a hexokinase method.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma insulin at 14 days
Venous blood samples will be taken and plasma insulin will be measured using a high-sensitivity human insulin ELISA.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma free fatty acids at 14 days
Venous blood samples will be taken and free fatty acids will be measured by colorimetric assay.
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline interleukin-1(IL)-1beta at 14 days
Mature IL-1beta secretion will be quantified by ELISA run in duplicate
Measured: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline caspase-1 activation at 14 days
Caspase-1 activation will be quantified by flow cytometry. The fluorescent inhibitor probe FAM-YVAD-FMK binds covalently to activated caspase-1 and emits at 530nm
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 posted25 Jan 2019
- Study start6 Feb 2019
- Primary completion1 Mar 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hyperglycemia, PostprandialStudies 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
- Prevention
- 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03817749
- Sponsor's protocol ID
- H18-02930
- Status last verified
- Apr 2021
- First submitted
- 6 Dec 2018
- Last updated
- 28 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The investigators will share individual patient data (de-identified) with researchers upon request.
Publications
Walsh JJ, Caldwell HG, Neudorf H, Ainslie PN, Little JP. Short-term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross-over trial. J Physiol. 2021 Nov;599(21):4763-4778. doi: 10.1113/JP281988. Epub 2021 Oct 4.
PubMed 34605026Walsh JJ, Neudorf H, Little JP. 14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial. J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1738-e1754. doi: 10.1210/clinem/dgaa925.
PubMed 33367782
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Exogenous Ketone Supplementation on Cardiovascular Function and Glucose Control
- ClinicalTrials.gov ID
- NCT03817749
- Acronym / sponsor ID
- H18-02930
- Keywords
- Flow mediated dilation, Glucose control, Inflammation, Immune cell function, Cognition, Oxidative stress, Cardiovascular function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 6 Feb 2019 (actual)
- Primary completion
- 1 Mar 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 25 Jan 2019 (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.
Post-prandial hyperglycemic excursions induce a cascade of deleterious effects on the body, including increased inflammation, production of reactive oxygen species, and impaired cardiovascular function. Ingestion of an exogenous oral ketone supplement blunts hyperglycemia in response to an oral glucose tolerance test. Accordingly, it is hypothesized that exogenous ketone supplement ingestion prior to a meal could be an effective strategy for blunting postprandial hyperglycemia. Therefore, the purpose of this study is to investigate the effect of short-term (14-days) pre-meal exogenous ketone supplementation on glucose control, cardiovascular function, inflammation, and oxidative stress in individuals at an elevated risk of type 2 diabetes.
Study design
- Primary purpose
- Prevention
- 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 monoester* Participants will consume 20 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 6 consecutive days during the supplementation period. |
| Placebo | Placebo comparator | Dietary Supplement: Exogenous ketone monoesterParticipants 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 (1 listed)
- Elevated waist circumference (>102 cm for males, >88 cm for females) and/or Obesity (BMI > 30 kg/m2) and/or Diagnoses of prediabetes based on A1C (5.7-6.4%) and/or fasting plasma glucose (5.6-6.9 mmol/l) using ADA criteria
Key exclusion criteria (10 listed)
- Competitively trained endurance athlete
- Actively attempting to lose weight
- History of mental illness or existing neurological disease(s)
- Previous cardiovascular events (i.e., heart attack, stroke)
- Diagnoses of diabetes
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: HVMN ketone monoester supplementParticipants will consume 20g 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, Placebo |
Primary outcome
Glucose control
Time frame: 2 hours after a meal
Post-prandial glucose excursions will be measured by continuous glucose monitoring using the iPro2 CGM by Medtronic in both the active and placebo supplement conditions. Post-prandial glucose following breakfast, lunch, and dinner will be averaged together.
9 secondary outcomes
Change from baseline flow mediated dilation at 14 days
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline histone acetylation at 14 days
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline mitochondrial superoxide production at 14 days
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline cognition (executive functions) at 14 days
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma glucose at 14 days
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 interleukin-1(IL)-1beta at 14 days
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline caspase-1 activation at 14 days
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 28 Apr 2021.
- Derived from this study: PubMed 34605026Walsh JJ, Caldwell HG, Neudorf H, Ainslie PN, Little JP. Short-term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross-over trial. J Physiol. 2021 Nov;599(21):4763-4778. doi: 10.1113/JP281988. Epub 2021 Oct 4.
- Derived from this study: PubMed 33367782Walsh JJ, Neudorf H, Little JP. 14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial. J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1738-e1754. doi: 10.1210/clinem/dgaa925.
- Individual participant dataSharing planned: Undecided. The investigators will share individual patient data (de-identified) with researchers upon 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.
The record lists no contact. Use the official record to reach the sponsor.
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 Hyperglycemia, Postprandial and Overweight and Obesity, 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 1 inclusion and 10 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 28 Apr 2021. 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 (time frame: 2 hours after a meal). 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 NCT03817749, which also lists 2 linked publications.
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 28 Apr 2021.