Clinical trial NCT06449287: Impact of Exogenous Ketones on Indices of Keto-Adaptation in Obese Subjects on Weight Reducing Diets.
Official title: Strategies to Augment Ketosis: Impact of Exogenous Ketones on Indices of Keto-Adaptation in Obese Subjects on Weight Reducing Diets.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ketogenic Diet
Weight Loss
Keywords: ketones
metabolism
weight loss
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2024-06-10
Enrollment: 37
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This project will be a three-group controlled 6-wk feeding study where all meals are prepared and provided to obese participants. All participants will be fed a 25% energy-restricted diet. Two diets will be very low in carbohydrate (i.e., ketogenic diets) designed to induce nutritional ketosis and fat loss. Another diet will be low in fat and saturated fat but contain the same total calories. Participants will be randomly assigned to a Ketone Supplement group who are provided an exogenous pre-formed source of beta-hydroxybutyrate (BOHB) or a Control group that only receives the standard ketogenic diet. Randomization will be stratified based on insulin resistance, sex, and body composition to ensure balanced group assignment. Because of timing of recruitment (i.e., after most of the ketogenic groups have already completed the study), the low-fat group will not be randomized. Outcome measurements will be made at various intervals over the 6-wk intervention.

Detailed description: This project will be a three-group controlled 6-wk feeding study where all meals are prepared and provided to obese participants. All participants will be fed a 25% energy-restricted diet. Two diets will be very low in carbohydrate (i.e., ketogenic diets) designed to induce nutritional ketosis and fat loss. Another diet will be low in fat and saturated fat but contain the same total calories. Participants will be randomly assigned to a Ketone Supplement group (n=12) who are provided an exogenous pre-formed source of beta-hydroxybutyrate (BOHB) or a Control group (n=12) that only receives the standard ketogenic diet. Randomization will be stratified based on insulin resistance, sex, and body composition to ensure balanced group assignment. Because of timing of recruitment (i.e., after most of the ketogenic groups have already completed the study), the low-fat group will not be randomized. Outcome measurements will be made at various intervals over the 6-wk intervention. Key outcome variables will include: 1) Markers of Ketosis/Keto-Adaptation: a. Daily measures of BOHB (capillary blood) b. Fasting serum BOHB and total ketones (venous blood) c. Diurnal capillary blood ketones and urinary loss of BOHB and total ketones 2) Energy Balance and Body Composition: a. Body mass (scale) b. Whole body and regional composition (DXA) c. Nitrogen balance (daily nitrogen intake - 24-hr urinary nitrogen loss) d. Resting energy expenditure and substrate oxidation (indirect calorimetry) e. Adiposity (myocardial/epicardial fat, liver fat, visceral fat, skeletal muscle fat by MRI) f. Microbiome (stool collection to observe microbiota and the response to diet alteration) 3) Cognitive and Behavioral: a. Computer-based cognitive function (ANAM) b. Behavioral responses (surveys) 4) Cardio-Metabolic Risk: a. Metabolic panel b. Circulating lipid panel (total cholesterol, LDL-C, HDL-C, TG) c. Glucose, insulin, HOMA

Eligibility criteria: Inclusion Criteria:

* BMI \>27 and =35 kg/m2

Exclusion Criteria:

* have diabetes, liver, kidney, or other metabolic or endocrine dysfunction, or using diabetic medications.
* Currently consuming a low-carbohydrate diet
* Weight loss of \>10% in past 6 months -Currently pregnant or nursing, or planning to become pregnant during the study
* Major psychiatric disorder (e.g., schizophrenia, bipolar disorder)
* Excessive alcohol intake (acute or chronic) defined as average consumption of 3 or more alcohol-containing beverages daily or consumption of more than 14 alcoholic beverages per week

Primary outcomes:
measure: Daily Ketone/Glucose Monitoring
timeFrame: Up to 6 weeks
measure: Cholesterol (mg/dl)
timeFrame: up to six weeks
measure: Insulin (mIU/L)
timeFrame: up to six weeks
measure: Glucose (mg/dL)
timeFrame: up to six weeks
measure: Lean Mass (kg)
timeFrame: up to six weeks
measure: Fat Mass (kg)
timeFrame: up to six weeks
Secondary outcomes:
measure: Neuropsychological Outcome 1 - Reaction time (Throughput)
timeFrame: up to six weeks
measure: Neuropsychological Outcome 1 - Visual Short Term Memory (Throughput)
timeFrame: up to six weeks
measure: Neuropsychological Outcome 1 - Spatial Processing (Throughput)
timeFrame: up to six weeks
measure: Urine Chemistries
timeFrame: up to 6 weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Jeff Volek, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kackley ML, Brownlow ML, Buga A, Crabtree CD, Sapper TN, O'Connor A, Volek JS. The effects of a 6-week controlled, hypocaloric ketogenic diet, with and without exogenous ketone salts, on cognitive performance and mood states in overweight and obese adults. Front Neurosci. 2022 Sep 30;16:971144. doi: 10.3389/fnins.2022.971144. eCollection 2022.
citation: Belany P, Kackley ML, Zhao S, Kluwe B, Buga A, Crabtree CD, Nedungadi D, Kline D, Brock G, Simonetti OP, Volek JS, Joseph JJ. Effects of Hypocaloric Low-Fat, Ketogenic, and Ketogenic and Ketone Supplement Diets on Aldosterone and Renin. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1727-1739. doi: 10.1210/clinem/dgad009.
citation: Buga A, Kackley ML, Crabtree CD, Bedell TN, Robinson BT, Stoner JT, Decker DD, Hyde PN, LaFountain RA, Brownlow ML, O'Connor A, Krishnan D, McElroy CA, Kraemer WJ, Volek JS. Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts. Clin Nutr ESPEN. 2023 Apr;54:277-287. doi: 10.1016/j.clnesp.2023.01.030. Epub 2023 Feb 4.