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Completed

NCT Number: NCT03817749

Ketone Supplementation, Glucose Control, and Cardiovascular Function

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.

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Key information

Conditions

Hyperglycemia, Postprandial Body Weight Diabetes Mellitus Risk Glucose Metabolism Disorders Hyperglycemia Inflammation Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Overweight and Obesity Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

30 year–69 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of British Columbia, Okanagan.

Kelowna, British Columbia, V1V 1V7, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Exogenous Ketone Monoester

Dietary 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.

Other names: HVMN ketone monoester supplement

Primary outcomes

  1. 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.

Secondary outcomes

  1. Change from baseline flow mediated dilation at 14 days

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

    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.

  2. Change from baseline histone acetylation at 14 days

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

    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).

  3. Change from baseline mitochondrial superoxide production at 14 days

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

    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)

  4. Change from baseline cognition (executive functions) at 14 days

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

    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.

  5. Change from baseline plasma glucose at 14 days

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

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

  6. Change from baseline plasma insulin at 14 days

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

    Venous blood samples will be taken and plasma insulin will be measured using a high-sensitivity human insulin ELISA.

  7. Change from baseline plasma free fatty acids at 14 days

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

    Venous blood samples will be taken and free fatty acids will be measured by colorimetric assay.

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

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

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

  9. Change from baseline caspase-1 activation at 14 days

    Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)

    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

Sponsors and collaborators

Lead sponsor

University of British Columbia

Other

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Jan 25, 2019
Registry last updated
Apr 28, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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