Impact of Exogenous Ketones on Indices of Keto-Adaptation in Obese Subjects on Weight Reducing Diets.

Weight Loss Clinical Trial

— STAK  

Official title:

Strategies to Augment Ketosis: Impact of Exogenous Ketones on Indices of Keto-Adaptation in Obese Subjects on Weight Reducing Diets.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06449287
• Other study ID #: 2017H0395
• Status: Completed
• Phase: N/A
• Start date: July 5, 2018
• Est. completion date: August 21, 2019

Study information

• Verified date: June 2024
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: August 21, 2019
• Est. primary completion date: March 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Body Weight
• Ketogenic Diet
• Weight Loss

Intervention

Other:
• Diet
The diet intervention will start after all baseline testing is complete

Biological:
• Blood Draw
Blood samples will be collected biweekly.
• Ketone/Glucose Monitoring
Hand-held glucometer will be used daily to monitor dietary intervention adherence.

Other:
• Body Composition
DEXA Scanning will be done pre-, mid-, and post- intervention.

Biological:
• Urine Analysis
24 hour urine collection will be done biweekly.

Behavioral:
• Neuropsychological Measures - ANAM
The first cognitive assessment will be done via Automated Neuropsychological Assessment Metrics (ANAM). This cognitive battery is a library of computer-based tests of domains including attention, concentration, reaction time, memory, processing speed, decision-making, and executive function.

Locations

Country	Name	City	State
United States	The Ohio State University	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Daily Ketone/Glucose Monitoring	Daily fasting glucose/ketones will be assessed using capillary finger stick lancing. A small drop of blood will be obtained once daily, while fasting, using enzymatic strips fitted for a handheld analyzer (KetoMojo). All the data will be stored in the device's internal memory.	Up to 6 weeks
Primary	Cholesterol (mg/dl)	Fasting venous blood will be collected biweekly to measure cholesterol.	up to six weeks
Primary	Insulin (mIU/L)	Fasting venous blood will be collected biweekly.	up to six weeks
Primary	Glucose (mg/dL)	Fasting venous blood will be collected biweekly.	up to six weeks
Primary	Lean Mass (kg)	DEXA Scanning will be biweekly to assess lean mass	up to six weeks
Primary	Fat Mass (kg)	DEXA Scanning will be biweekly to assess fat mass	up to six weeks
Secondary	Neuropsychological Outcome 1 - Reaction time (Throughput)	The first cognitive assessment will be done via Automated Neuropsychological Assessment Metrics (ANAM). Measures SRT by presenting the user with a series of "*" symbols to which they must respond as quickly as possible each time the symbol appears. Results are measured by throughput.	up to six weeks
Secondary	Neuropsychological Outcome 1 - Visual Short Term Memory (Throughput)	The first cognitive assessment will be done via Automated Neuropsychological Assessment Metrics (ANAM). Measures verbal short-term memory by having the users memorize a set of characters and then indicate as single characters are presented on the screen whether the character was part of the memory set. Results are measured by throughput.	up to six weeks
Secondary	Neuropsychological Outcome 1 - Spatial Processing (Throughput)	The first cognitive assessment will be done via Automated Neuropsychological Assessment Metrics (ANAM). Measures visual spatial skills and mental rotation by having the users compare the equivalence of two 4-bar histograms, the first of which is displayed upright and the second of which is displayed after a 90° rotation either clockwise or counterclockwise. Results are measured by Throughput.	up to six weeks
Secondary	Urine Chemistries	24 hour urine will be collected biweekly and analyzed for urine chemistries	up to 6 weeks