Examining the Feasibility of Prolonged Ketone Concentrate Supplement Drink Consumption in Adults With Type 2 Diabetes

Brief Summary:

Ketones are a source of energy and signaling molecule that are produced by the body when not consuming any food or consistently eating 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 how different cells in the body function.

Recently, ketone supplements have been developed that can be consumed as a drink. These supplements can raise blood ketones without having to fast or eat a "keto" diet. Previous studies have shown that these supplement drinks can lower blood sugar without having to make any other dietary changes. Drinking these ketone supplements may therefore be an effective strategy to improve blood sugar control and influence how cells function.

To find out if it is feasible for people with type 2 diabetes to drink these ketones supplements regularly over 90 days, we will compare between two groups in this study: one group that will be asked to drink ketone supplements, and one group that will be asked to drink a placebo supplement.

Study Overview

• Status: Active, not recruiting
• Conditions: Hyperglycemia; Diabetes Mellitus, Type 2; Ketosis
• Intervention / Treatment: Dietary supplement: Dietary Supplement: D-β-hydroxybutyric acid with R-1,3-butanediol; Other: Inert placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1V 1V7
      • University of British Columbia Okanagan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• diagnosed with type 2 diabetes by a physician at least 1 year prior
• stable use of glucose-lowering medications for at least three months
• must be able to read and understand English in order to complete the study questionnaires

Exclusion Criteria:

• competitively trained endurance athlete
• actively attempting to gain or lose weight
• having a history of mental illness or existing neurological disease
• having a history of cardiovascular events in the last two years, hypoglycemia, irritable bowel syndrome, or inflammatory bowel disease
• are currently taking SGLT2 inhibitors or insulin
• are using more than 2 classes of glucose-lowering medication
• currently following a ketogenic diet or regularly taking ketone supplements
• unable to commit to a 90-day trial
• being unable to follow remote guidance by internet or smartphone
• currently taking natural or over-the-counter supplements specifically designed to lower blood glucose (e.g., berberine, bitter melon)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Exogenous Ketone Supplement; Participants will be instructed to consume a total of 177 mL of the exogenous ketone supplement drink (for a total of 30 g of beta-hydroxybutyrate) per day (3 doses at 59 mL containing 10 g of beta-hydroxybutyrate each) for a period of 90 days.	Dietary supplement: Dietary Supplement: D-β-hydroxybutyric acid with R-1,3-butanediol; Pre-intervention (baseline) and post-intervention measurements will be obtained before and after the 90-day period respectively.
Placebo Comparator: Placebo Comparator: Inert placebo; Participants will be instructed to consume an equivalent volume (177 mL) of taste- and volume-matched placebo per day (3 doses at 59 mL) for 90 days.	Other: Inert placebo; Pre-intervention (baseline) and post-intervention measurements will be obtained before and after the 90-day period respectively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the feasibility of conducting a randomized controlled trial (RCT) on the effects of consumption of a ketone supplement in adults with type 2 diabetes in free-living environment for 90 days: Recruitment rate of participants into the trial	A recruitment rate of at least 4 participants per month (which will ensure the study is fully enrolled within a 1-year timeline) will be acceptable.	Start of enrolment to completion of enrolment
To determine the feasibility of conducting such an RCT: Compliance as measured by the self-reported volume of ketone supplement drink consumed	≥ 67% of the drinks provided being consumed by participants as determined via self-report (i.e., an average of two out of three drinks per day being consumed) will be acceptable.	Across the 90-day intervention period (days 0 through 90)
To determine the feasibility of conducting such an RCT: Retention as measured by the number of participants that complete the study	≤ 30% of recruited participants dropping out of the study will be acceptable	Across the 90-day intervention period (days 0 through 90)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures of glycemic control (HbA1c)	Glycemic control will be measured by assessing HbA1c in a clinical laboratory.	Day 0 (pre-intervention/baseline) and day 90 (post-intervention/follow-up)
Supplement acceptability	Supplement acceptability will be assessed via questionnaire.	Days 1, 45, and 90
Gastrointestinal distress	Gastrointestinal distress will be assessed via questionnaire.	Days 1, 45, and 90
Self-reported body weight	Self-reported body weight will be assessed by questionnaire.	Day 0 (pre-intervention/baseline) and day 90 (post-intervention/follow-up)
Self-reported energy consumption	Self-reported energy consumption will be assessed via 24-hour dietary recalls.	Days 0 (pre-intervention/baseline), 45, and 90
Levels of perceived hunger	Levels of perceived hunger will be assessed via questionnaire.	Days 0 (pre-intervention/baseline), 45, and 90
High-sensitivity c-reactive protein	High-sensitivity c-reactive protein will be measured in a clinical laboratory.	Day 0 (pre-intervention/baseline) and day 90 (post-intervention/follow-up)
Hematology panel	Hematology panel will be measured in a clinical laboratory.	Day 0 (pre-intervention/baseline) and day 90 (post-intervention/follow-up)
Liver enzymes (ALT, AST)	Liver enzymes (ALT, AST) will be measured in a clinical laboratory.	Day 0 (pre-intervention/baseline) and day 90 (post-intervention/follow-up)
Lipid panel (triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high density lipoprotein cholesterol, cholesterol/high-density lipoprotein cholesterol ratio)	Lipid panel will be measured in a clinical laboratory.	Day 0 (pre-intervention/baseline) and day 90 (post-intervention/follow-up)
Theory of planned behaviour	Theory of planned behaviour will be assessed via questionnaire.	Days 0 (pre-intervention/baseline) and 45
Sleep quality	Sleep quality will be assessed via questionnaire.	Days 0 (pre-intervention/baseline), 45, and 90
Cravings	Cravings will be assessed via questionnaire.	Days 0 (pre-intervention/baseline), 45, and 90
Self-rated health	Self-rated health and its impacts on daily life will be assessed via questionnaire.	Days 0 (pre-intervention/baseline), 45, and 90
Self-reported blood pressure (systolic and diastolic)	Self-reported blood pressure (systolic and diastolic) will be assessed via questionnaire (via study-provided blood pressure monitors).	Days 0 (pre-intervention/baseline), 45, and 90
Measures of glycemic control (postprandial glucose area under the curve)	Glycemic control will be measured by continuous glucose monitoring using the FreeStyle Libre 2 (Abbott) and quantified by assessing 2-hour postprandial hyperglycemia.	Days -5 through 9 (5 days of baseline and first 9 days of intervention period) and days 77 through 90 (last 2 weeks)
Measures of glycemic control (average daily glucose)	Glycemic control will be measured by continuous glucose monitoring using the FreeStyle Libre 2 (Abbott) and quantified by assessing the average daily glucose.	Days -5 through 9 (5 days of baseline and first 9 days of intervention period) and days 77 through 90 (last 2 weeks)
Measures of glycemic control (glucose variability)	Glycemic control will be measured by continuous glucose monitoring using the FreeStyle Libre 2 (Abbott) and quantified by assessing glucose variability.	Days -5 through 9 (5 days of baseline and first 9 days of intervention period) and days 77 through 90 (last 2 weeks)
Self-reported waist circumference	Self-reported waist circumference will be assessed by questionnaire (using study-provided measurement tape).	ay 0 (pre-intervention/baseline) and day 90 (post-intervention/follow-up)
Levels of physical activity	Theory of planned behaviour will be assessed via questionnaire.	Days 0 (pre-intervention/baseline) and 45
Overall acceptability	Will be assessed via an open ended questionnaire either at completion time or in case of withdrawal	Day 90 or in case of withdrawal

Collaborators and Investigators

• Sponsor: University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: July 4, 2023
• First Submitted That Met QC Criteria: August 1, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: RKT2D_concentrate

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will share individual patient data (de-identified) with researchers upon reasonable request.
• IPD Sharing 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.
• IPD Sharing 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).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No