Ketone Supplementation, Glucose Control, and Cardiovascular Function

Overweight and Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03817749
• Other study ID #: H18-02930
• Status: Completed
• Phase: N/A
• Start date: February 6, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: April 2021
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 31, 2020
• Est. primary completion date: March 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus Risk
• Hyperglycemia
• Hyperglycemia, Postprandial
• Overweight
• Overweight and Obesity

Intervention

Dietary Supplement:
• Exogenous ketone monoester
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.

Locations

Country	Name	City	State
Canada	University of British Columbia, Okanagan.	Kelowna	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 hours after a meal
Secondary	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.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	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).	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	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)	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	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.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Change from baseline plasma glucose at 14 days	Venous blood samples will be taken and plasma glucose will be measured using a hexokinase method.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	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.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	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.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Change from baseline interleukin-1(IL)-1beta at 14 days	Mature IL-1beta secretion will be quantified by ELISA run in duplicate	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	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	Day 0 (Pre-intervention) and Day 14 (post-intervention)