Ketone Supplementation, Glucose Control, and Cardiovascular Function

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Exogenous ketone monoester

About this trial

This is an interventional prevention trial for Hyperglycemia, Postprandial focused on measuring Flow mediated dilation, Glucose control, Inflammation, Immune cell function, Cognition, Oxidative stress, Cardiovascular function

Eligibility Criteria

30 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Sites / Locations

University of British Columbia, Okanagan.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental

Placebo

Arm Description

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.

Participants will consume a flavor matched placebo drink and undergo the same procedures described in the Experimental Arm

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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).

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)

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.

Change from baseline plasma glucose at 14 days

Venous blood samples will be taken and plasma glucose will be measured using a hexokinase method.

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.

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.

Change from baseline interleukin-1(IL)-1beta at 14 days

Mature IL-1beta secretion will be quantified by ELISA run in duplicate

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

Full Information

NCT ID

NCT03817749

First Posted

December 6, 2018

Last Updated

April 26, 2021

Sponsor

University of British Columbia

1. Study Identification

Unique Protocol Identification Number

NCT03817749

Brief Title

Ketone Supplementation, Glucose Control, and Cardiovascular Function

Official Title

The Effects of Exogenous Ketone Supplementation on Cardiovascular Function and Glucose Control

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

February 6, 2019 (Actual)

Primary Completion Date

March 1, 2020 (Actual)

Study Completion Date

December 31, 2020 (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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperglycemia, Postprandial, Overweight and Obesity, Diabetes Mellitus Risk

Keywords

Flow mediated dilation, Glucose control, Inflammation, Immune cell function, Cognition, Oxidative stress, Cardiovascular function

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will consume a flavor matched placebo drink and undergo the same procedures described in the Experimental Arm

Intervention Type

Dietary Supplement

Intervention Name(s)

Exogenous ketone monoester

Other Intervention Name(s)

HVMN ketone monoester supplement

Intervention Description

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.

Primary Outcome Measure Information:

Title

Glucose control

Description

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.

Time Frame

2 hours after a meal

Secondary Outcome Measure Information:

Title

Change from baseline flow mediated dilation at 14 days

Description

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.

Time Frame