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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Diabetes Mellitus, Type 2, Hyperglycemia, Ketosis

Intervention / Treatment
-----------------
* Dietary Supplement: Dietary Supplement: D-β-hydroxybutyric acid with R-1,3-butanediol
* Other: Inert placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Exogenous Ketone Supplement<br>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<br>* Pre-intervention (baseline) and post-intervention measurements will be obtained before and after the 90-day period respectively.<br>|
| Placebo Comparator: Placebo Comparator: Inert placebo<br>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<br>* Pre-intervention (baseline) and post-intervention measurements will be obtained before and after the 90-day period respectively<br>|

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) | 
| 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) | 
| 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 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) | 
| 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) | 
| Levels of physical activity | 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 | 
| Theory of planned behaviour | 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 |