Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06327464
Status:
RECRUITING
Last Update Posted:
2024-05-08
First Post:
2024-02-23
Brief Title:
Exogenous Ketones and Appetite
Sponsor:
University of British Columbia
Organization:
University of British Columbia
Study Overview
Official Title:
The Effect of Exogenous Ketones on Appetite in Adults With or Without Obesity
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
People with obesity have different appetitive responses to stimuli compared to people without obesity For example people with obesity have a blunted postprandial ghrelin hunger hormone response lower glucagon-like peptide 1 GLP-1 and peptide-YY PYY associated with satiety compared to people without obesity Given the favorable effects of exogenous ketones on appetite previously observed in healthy adults of normal body weight it is possible that these supplements can alter appetite hormones in a manner that may closer match that observed in people without obesity To explore this research question investigators will conduct a randomized single-blind cross over study to characterize appetite and dietary intake after ingestion of an exogenous ketone supplement within adults with obesity compared a control condition without exogenous ketones and compared to adults without obesity The research team will also explore differences in postprandial energy expenditure and fuel utilization Twenty-two healthy young- and middle-aged adults will be included up to n26 enrolled In addition to a baseline visit to measure body composition participants will undergo two 45-hour study visits one of which will include a ketone diol supplement and one will have a placebo Participants will be given a 1-day run-in diet prior to each study day to support energy balance On each study day visit participants will undergo a resting metabolic rate test indirect calorimetry followed by a fasting appetite rating and blood sample collection Participants will then be provided with a standard breakfast meal one with the ketone supplement and one with placebo Appetite ratings and blood sample collection will be repeated 60 120 and 180 minutes after the meal Indirect calorimetry will be completed after the 30 90 and 150 minute assessments After the 180-minute timepoint participants will be provided with a buffet-like lunch meal with instructions to eat as much or as little as they would like to determine ad libitum dietary intake at a single meal To assess free-living ad libitum dietary intake participants will receive 15 days of food boxes tailored to their preferences with uneaten food returned at the end of the 15-day period This study will be the first to assess the impact of exogenous ketones on appetite in obesity and would help inform future weight loss intervention trials
Detailed Description:
Overview
Investigators will conduct a randomized single-blind cross-over study in adults with and without obesity The study consists of one screeningbaseline visit plus two 45-hour in-lab appetite visits one with the exogenous ketone supplement and one without After the baselinescreening visit individuals will be randomized to either placeboketone or ketoneplacebo study visit order in a 11 manner using online software httpwwwrandomizationcom A washout period of at least 7 days will occur between study visits For females every attempt will be made to book these visits in the same menstrual cycle phase according to self-reported menstrual cycle history or estimated phase for individuals not taking hormonal contraceptives or with a hormonal IUD
Screening and baseline visit 1 hour
Individuals who consent to enroll in the study will be scheduled for a 1 hour visit to confirm eligibility measure body composition and review study day procedures Height and weight will be collected to confirm eligibility Participants will also complete questionnaires to collect data on basic demographics and medical history menstrual cycle history for females food preferences for the run-in and study day diets screening for disordered eating EATS-26 and alcohol or drug abuse CAGE
Data on participants fat mass FM fat-free mass FFM body fat percent and bone mineral density will be collected using a full body dual X-ray absorptiometry DEXA Hologic Model A Body composition variables will be expressed in absolute terms and controlling for height eg FM index FM kgheight m2 FFM will also be expressed in relation to FM FMFFM
Run-in energy balanced diet A 1-day energy-balanced run-in diet will be provided to each participant prior to each study day Diets will be modified according to participant preferences and the same diet will be given on the second run-in day The caloric value of the diet will be determined using the 2023 dietary reference intake equations with self-identified activity factor collected at the screening and baseline visit and will have a macronutrient composition of 50 carbohydrate 30 fat and 20 protein This baseline dietary control period will ensure energy balance and weight maintenance prior to each study day All meals will be prepared by a third-party dietary meal prep company in Kelowna
Study visit days 45-5 hours
Participants will be asked to refrain from food and calorie- or caffeine-containing beverages for at least 12 hours alcohol for at least 24 hours and vigorous-intensity exercise for at least 48 hours before each study visit Each study day visit will be scheduled to start sometime between 7 - 930am depending on scheduling availability and usual participant wake time both visits will be scheduled at approximately the same time All study day procedures will be conducted on the first floor of RHS in the following order
Body weight on a digital scale measured without shoes or heavy clothing items
Resting metabolic rate will be measured for 15-20 minutes after a period of 25-30 minutes of quiet rest using an indirect calorimeter metabolic cart with face mask ParvoMedics TrueOne 240 This test measures oxygen consumed and to estimate resting metabolic rate in kilocaloriesday During the test participants breathe normally through a facemask while relaxed but not falling asleep
The following procedures will be completed after the resting metabolic rate test but before breakfast timepoint -5 fasted sample and 60 120 and 180 minutes after breakfast is consumed
Serial blood sampling First a 22-gauge intravenous IV catheter will be placed in the antecubital area of the arm or dorsal side of the hand For each timepoint two 3-mL tubes pretreated ethylenediaminetetraacetic acid EDTA labeled with the participants study ID study number date and time will be collected 06 mg AEBSF inhibitor will be immediately added to one sample and 0 μL Dipeptidyl peptidase-IV inhibitor and 005 mL of aprotinin will be added to the other sample These samples will be immediately placed on ice stored in a -80 freezer until analyses The following appetite hormones will be assessed acylated ghrelin PYY radioimmunoassay GLP-1 7-36 leptin and insulin enzyme-linked immunoassay ELISA
Circulating concentrations of glucose and D-β-hydroxybutyrate ketone concentrations will be collected using a glucose and ketone monitoring system Fora 6 Connect
Appetite ratings will be completed using visual analogue scale VAS questions about hunger fullness prospective food consumption and desire to eat on a sliding scale on a university-owned iPad Questions will be from Flint et al In J Obes 2000 2438-48 and are standard procedure in the greater appetite literature
Additional 30-minute assessments of postprandial energy expenditure and fuel utilization will be collected using indirect calorimetry after the 30 90 and 120-minute time points Postprandial energy expenditure assessments will be expressed relative to the resting metabolic rate values
Standard breakfast meal Participants will be given a standard breakfast meal consisting of a protein bar juice and mixed nuts or similar substitutes in case of food intolerancesallergies The energy content of the breakfast in both conditions ketone and placebo will be designed to meet 25 of each individuals estimated total energy requirements calculated from the 2023 Dietary Reference Intake equations In the placebo condition the macronutrient composition of 50 carbohydrate 30 fat and 20 protein In the ketone condition 70 kcal of carbohydrate will be removed from the breakfast and replaced with the 70-kcal Ketone-IQ supplement Participants will have up to 20 minutes to consume this meal in a private and quiet location and may not use personal devices computers or read during this time to avoid the influence of external stimuli on dietary intake
Exogenous ketone and placebo supplements will be delivered in liquid form and consumed orally with the breakfast meal Both drinks will be diluted to 500mL with a commercially available calorie-free drink Mio Kraft-Heinz Chicago IL The ketone supplement R-13-butanediol HVMN Ketone 20 and taste-matched calorie-free placebo will be provided by HVMN
Ad libitum dietary intake at a single lunch meal At the end of the 180-minute time point participants will be offered a buffet-style lunch with pre-weighed food items including pre-packaged spaghetti with sauce eg Stouffers or similar dinner rolls butter fresh fruit salad or steamed vegetables cookies chips juice granola bars and regular and diet soda Participants will be asked to consume as much or as little as they like until comfortably full and can request more of any item The meal will be consumed in isolation with no distractions or and the use of computers or mobile phones At the end of the buffet meal leftover food will be weighed and absolute energy and macronutrient intake will be determined by calculating the weighed difference of each food item before and after each meal
Post-study day visit dietary intake assessment
Ad libitum dietary intake Participants will be provided with 15 days of meals and snacks to begin consuming after the study day visit Participants will be instructed to eat as little or as much as they would like in free-living settings Meals will be provided by a local meal delivery service and supplemented with snacks and beverages purchased by the study team The content of the provided food will be identical between visits and be determined according to participants reported eating habits excluding both top-rated foods and disliked ones to avoid over- and under- consumption Participants will be asked to only eat the food provided and return empty containers and remaining food at the end of the 15-day period They will be provided with a paper form and food scale to record any foods that were consumed that were not provided
Investigators will conduct a randomized single-blind cross-over study in adults with and without obesity The study consists of one screeningbaseline visit plus two 45-hour in-lab appetite visits one with the exogenous ketone supplement and one without After the baselinescreening visit individuals will be randomized to either placeboketone or ketoneplacebo study visit order in a 11 manner using online software httpwwwrandomizationcom A washout period of at least 7 days will occur between study visits For females every attempt will be made to book these visits in the same menstrual cycle phase according to self-reported menstrual cycle history or estimated phase for individuals not taking hormonal contraceptives or with a hormonal IUD
Screening and baseline visit 1 hour
Individuals who consent to enroll in the study will be scheduled for a 1 hour visit to confirm eligibility measure body composition and review study day procedures Height and weight will be collected to confirm eligibility Participants will also complete questionnaires to collect data on basic demographics and medical history menstrual cycle history for females food preferences for the run-in and study day diets screening for disordered eating EATS-26 and alcohol or drug abuse CAGE
Data on participants fat mass FM fat-free mass FFM body fat percent and bone mineral density will be collected using a full body dual X-ray absorptiometry DEXA Hologic Model A Body composition variables will be expressed in absolute terms and controlling for height eg FM index FM kgheight m2 FFM will also be expressed in relation to FM FMFFM
Run-in energy balanced diet A 1-day energy-balanced run-in diet will be provided to each participant prior to each study day Diets will be modified according to participant preferences and the same diet will be given on the second run-in day The caloric value of the diet will be determined using the 2023 dietary reference intake equations with self-identified activity factor collected at the screening and baseline visit and will have a macronutrient composition of 50 carbohydrate 30 fat and 20 protein This baseline dietary control period will ensure energy balance and weight maintenance prior to each study day All meals will be prepared by a third-party dietary meal prep company in Kelowna
Study visit days 45-5 hours
Participants will be asked to refrain from food and calorie- or caffeine-containing beverages for at least 12 hours alcohol for at least 24 hours and vigorous-intensity exercise for at least 48 hours before each study visit Each study day visit will be scheduled to start sometime between 7 - 930am depending on scheduling availability and usual participant wake time both visits will be scheduled at approximately the same time All study day procedures will be conducted on the first floor of RHS in the following order
Body weight on a digital scale measured without shoes or heavy clothing items
Resting metabolic rate will be measured for 15-20 minutes after a period of 25-30 minutes of quiet rest using an indirect calorimeter metabolic cart with face mask ParvoMedics TrueOne 240 This test measures oxygen consumed and to estimate resting metabolic rate in kilocaloriesday During the test participants breathe normally through a facemask while relaxed but not falling asleep
The following procedures will be completed after the resting metabolic rate test but before breakfast timepoint -5 fasted sample and 60 120 and 180 minutes after breakfast is consumed
Serial blood sampling First a 22-gauge intravenous IV catheter will be placed in the antecubital area of the arm or dorsal side of the hand For each timepoint two 3-mL tubes pretreated ethylenediaminetetraacetic acid EDTA labeled with the participants study ID study number date and time will be collected 06 mg AEBSF inhibitor will be immediately added to one sample and 0 μL Dipeptidyl peptidase-IV inhibitor and 005 mL of aprotinin will be added to the other sample These samples will be immediately placed on ice stored in a -80 freezer until analyses The following appetite hormones will be assessed acylated ghrelin PYY radioimmunoassay GLP-1 7-36 leptin and insulin enzyme-linked immunoassay ELISA
Circulating concentrations of glucose and D-β-hydroxybutyrate ketone concentrations will be collected using a glucose and ketone monitoring system Fora 6 Connect
Appetite ratings will be completed using visual analogue scale VAS questions about hunger fullness prospective food consumption and desire to eat on a sliding scale on a university-owned iPad Questions will be from Flint et al In J Obes 2000 2438-48 and are standard procedure in the greater appetite literature
Additional 30-minute assessments of postprandial energy expenditure and fuel utilization will be collected using indirect calorimetry after the 30 90 and 120-minute time points Postprandial energy expenditure assessments will be expressed relative to the resting metabolic rate values
Standard breakfast meal Participants will be given a standard breakfast meal consisting of a protein bar juice and mixed nuts or similar substitutes in case of food intolerancesallergies The energy content of the breakfast in both conditions ketone and placebo will be designed to meet 25 of each individuals estimated total energy requirements calculated from the 2023 Dietary Reference Intake equations In the placebo condition the macronutrient composition of 50 carbohydrate 30 fat and 20 protein In the ketone condition 70 kcal of carbohydrate will be removed from the breakfast and replaced with the 70-kcal Ketone-IQ supplement Participants will have up to 20 minutes to consume this meal in a private and quiet location and may not use personal devices computers or read during this time to avoid the influence of external stimuli on dietary intake
Exogenous ketone and placebo supplements will be delivered in liquid form and consumed orally with the breakfast meal Both drinks will be diluted to 500mL with a commercially available calorie-free drink Mio Kraft-Heinz Chicago IL The ketone supplement R-13-butanediol HVMN Ketone 20 and taste-matched calorie-free placebo will be provided by HVMN
Ad libitum dietary intake at a single lunch meal At the end of the 180-minute time point participants will be offered a buffet-style lunch with pre-weighed food items including pre-packaged spaghetti with sauce eg Stouffers or similar dinner rolls butter fresh fruit salad or steamed vegetables cookies chips juice granola bars and regular and diet soda Participants will be asked to consume as much or as little as they like until comfortably full and can request more of any item The meal will be consumed in isolation with no distractions or and the use of computers or mobile phones At the end of the buffet meal leftover food will be weighed and absolute energy and macronutrient intake will be determined by calculating the weighed difference of each food item before and after each meal
Post-study day visit dietary intake assessment
Ad libitum dietary intake Participants will be provided with 15 days of meals and snacks to begin consuming after the study day visit Participants will be instructed to eat as little or as much as they would like in free-living settings Meals will be provided by a local meal delivery service and supplemented with snacks and beverages purchased by the study team The content of the provided food will be identical between visits and be determined according to participants reported eating habits excluding both top-rated foods and disliked ones to avoid over- and under- consumption Participants will be asked to only eat the food provided and return empty containers and remaining food at the end of the 15-day period They will be provided with a paper form and food scale to record any foods that were consumed that were not provided
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None