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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Effect of 14 Days of Exogenous Ketone Supplementation on Glycemic Control in Type 2 Diabetes: a Randomized Placebo-controlled Crossover Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05155410
• Other study ID #: H21-01762
• Status: Completed
• Phase: N/A
• Start date: February 15, 2022
• Est. completion date: February 3, 2023

Study information

• Verified date: April 2023
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: February 3, 2023
• Est. primary completion date: February 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 69 Years

Eligibility

Inclusion Criteria:

• Have a type 2 diabetes diagnosis from a physician

• Have stable use of glucose-lowering medications for at least 3 months

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Dietary Supplement:
• Exogenous Ketone Monoester
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.
• Placebo
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.

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
Other	Supplement acceptability	Acceptability of the supplement (easy of compliance, taste etc.) will be assessed via questionnaire. A 7-point Likert scale will be used.	Day 14
Other	Hunger and fullness cravings questionnaire	Perceived hunger will be measured on a visual analogue scale questionnaire assessing hunger and fullness. The questions assessed are: How hungry do you feel? (0 = I am not hungry at all; 10 = I have never been more hungry); How satisfied do you feel? (0 = I am completely empty; 10 = I cannot eat another bite); How full do you feel? (0 = Not at all full; 10 = Totally full); How much more do you think you can eat? (0 = Nothing at all; 10 = A lot)	Day 0 (Pre-intervention) through to Day 3
Other	T cell Activation	Markers of T cell activation in whole blood will be quantified by flow cytometry.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Other	Cravings	Participants will be asked to report their desire to eat a particular type of food. A visual analogue scale will be used. The questions assessing cravings are: How often do you experience strong urges to eat particular types of food? (0 = Never; 10 = All the time); On average how often do you experience a strong urge to eat a particular type of food? (0 = Several times per day; 10 = Once per month); How strong are these urges you experience to eat particular types of food? (0 = Extremely weak; 10 = Extremely strong); Are the experiences of strong urges to eat a particular food always of the same strength? (0 = Never; 10 = Always); How easy is it to ignore this strong urge to eat a particular food? (0 = Very easy; 10 = Impossible); Is a strong urge to eat a particular food the same as a craving for food? (0 = No; 10 = Yes)	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Primary	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	Vascular function	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	Cognition: N-back test	Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the computer-based app Inqisit6 Lab (Millisecond). The test will be the n-back test.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Cognition: Digit-symbol substitution test	Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the computer-based app Inquisit6 Lab (Millisecond). The test will be the digit-symbol substitution test.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Change from baseline plasma insulin at 14 days	Plasma insulin from venous blood samples will be measured using a high-sensitivity human insulin enzyme-like immunosorbent assay (ELISA) run in duplicate.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Change from baseline plasma free fatty acids at 14 days	Free fatty acids from venous blood samples will be measured by colorimetric assay run in duplicate.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Change from baseline circulating inflammatory cytokines at 14 days	Key inflammatory cytokines including CRP will be quantified by Mesoscale Discovery U-PLEX run in duplicate.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Phagocytosis	Phagocytosis of fluorescent-labelled E. coli by immune cells from whole blood will be quantified by flow cytometry	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Oxidative Burst	LPS-stimulated oxidative burst by immune cells from whole blood will be quantified by flow cytometry	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Degranulation	Immune cell degranulation will be quantified by enzyme-linked immunosorbent assay run in duplicate (quantifying myeloperoxidase and elastase in whole blood cell culture supernatants).	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Immune Cell Phenotyping	Phenotyping of macrophages and T cells will be quantified by surface and intracellular staining by flow cytometry.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Complete blood count	A 5-part white blood cell differential and complete blood count will be quantified by hematology analyzer.	Day 0 (Pre-intervention) and Day 14 (post-intervention)
Secondary	Glycemic Control: 2hr postprandial hyperglycemia	Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing 2hr postprandial hyperglycemia.	Day 1 through to Day 10
Secondary	Glycemic Control: 24hr average glucose area under the curve (AUC)	Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing 24hr average glucose AUC.	Day 1 through to Day 10
Secondary	Glycemic Control: Fasting glucose	Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing fasting plasma glucose.	Day 1 through to Day 10
Secondary	Glycemic Control: Change in Fasting Plasma glucose	Change in fasting plasma glucose (from pre-intervention Day 0) will be measured by fasting blood sample in both the active and placebo supplement conditions.	Day 14
Secondary	Glycemic Control: Glycemic variability	Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing glycemic variability.	Day 1 through to Day 10
Secondary	Glycemic Control: Time in Target Range	Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing time in target range.	Day 1 through to Day 10
Secondary	Glycemic Control: HbA1c	Glycemic control will be measured by assessing HbA1c using a point-of-care analyzer.	Day 0 (pre-intervention) and Day 14 (post-intervention)
Secondary	Lipid Panel	Lipid panel (total cholesterol, high-density cholesterol, low-density cholesterol, triglycerides, non-HDL cholesterol, cholesterol/HDL ratio) will be measured using a point-of-care analyzer.	Day 0 (pre-intervention) and Day 14 (post-intervention)
Secondary	Body weight	Change in body weight will be measured using a body weight scale.	Day 0 (pre-intervention) and Day 14 (post-intervention)
Secondary	Blood pressure	Change in blood pressure will be measured using an automated blood pressure device. Both systolic and diastolic blood pressure will be measured.	Day 0 (pre-intervention) and Day 14 (post-intervention)
Secondary	Blood beta-hydroxybutyrate	Change in fasting blood beta-hydroxybutyrate will be measured using a standard assay.	Day 0 (pre-intervention) and Day 14 (post-intervention)
Secondary	Physical activity	Physical activity will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.	Day 0 (pre-intervention) to Day 14 (post-intervention)
Secondary	Sedentary time	Sedentary time will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.	Day 0 (pre-intervention) to Day 14 (post-intervention)
Secondary	Sleeping time	Sleeping time will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.	Day 0 (pre-intervention) to Day 14 (post-intervention)
Secondary	Resting heart rate	Change resting heart rate will be measured using an automated heart rate monitor device.	Day 0 (pre-intervention) and Day 14 (post-intervention)
Secondary	Waist circumference	Change in waist circumference will be measures using a measurement tape.	Day 0 (pre-intervention) and Day 14 (post-intervention)