Examining the Effect of Exogenous Ketone Supplementation on Glucose Control in Type 2 Diabetes

NCT05155410 | Completed

• 1 other identifier: H21-01762
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

3-Hydroxybutyric Acid; Glycemic Control; Hyperglycemia; Ketones; Glucose Control; Inflammation; Immune cell function; Cognition

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 14 (post-intervention)

Secondary Outcomes (27)

• Vascular function

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

• Cognition: N-back test

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

• Cognition: Digit-symbol substitution test

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

• Change from baseline plasma insulin at 14 days

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

• Change from baseline plasma free fatty acids at 14 days

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

Other Outcomes (4)

• Supplement acceptability

  Day 14

• Hunger and fullness cravings questionnaire

  Day 0 (Pre-intervention) through to Day 3

• T cell Activation

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

Study Arms (2)

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.

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

Dietary Supplement: Placebo

Interventions

Exogenous Ketone Monoester DIETARY_SUPPLEMENT

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.

Also known as: KetoneAid KE4 Ketone Ester, D-β-hydroxybutyrate-R 1,3-Butanediol

Experimental

Placebo DIETARY_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.

Also known as: Flavor- and volume-matched placebo supplement

Placebo

Eligibility Criteria

• Age: 30 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a type 2 diabetes diagnosis from a physician
• Have stable use of glucose-lowering medications for at least 3 months

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia Okanagan

Kelowna, British Columbia, V1V 3G1, Canada

Location

Related Publications (1)

• 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.

  PMID: 39804761 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hyperglycemia; Ketosis; Inflammation

Interventions

Flavoring Agents

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Acidosis; Acid-Base Imbalance; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Food Additives; Food Ingredients; Specialty Uses of Chemicals; Chemical Actions and Uses; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Jonathan Little, PhD

  University of British Columbia- Okanagan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: November 30, 2021
• First Posted: December 13, 2021
• Study Start: February 15, 2022
• Primary Completion: February 3, 2023
• Study Completion: February 3, 2023
• Last Updated: April 13, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The de-identified data and associated documents will be made available to researchers upon reasonable request for the duration that is required by the researchers.
• Access Criteria: Researchers from accredited institutions will be granted access to the de-identified data and associated documents provided they can show that it will be used for a research-related purpose (e.g., meta-analysis).

Locations

CA (1)