Strategies to Augment Ketosis: Optimization of Ketone Delivery Strategies (STAK: OK'd)

May 28, 2026 updated by: Jeff Volek, Ohio State University
One important difference between KE compounds is the ketone-promoting components, which determines the circulating ratio of blood ketone bodies, BHB and AcAc, and may in turn lead to important metabolic and signaling differences. Whereas some actions of the ketone bodies BHB and AcAc are shared, R-BHB has a broad range of signaling functions that are distinct from AcAc, some of which are shared by the non-circulating, non-oxidizable enantiomer, S-BHB. AcAc also has metabolic and signaling actions that are independent of BHB and is selectively oxidized in some cells that cannot oxidize BHB. Furthermore, responses to different ketone bodies vary between tissue types. A second difference between KE arises from the balance between direct delivery of ketones compared to indirectly elevating ketone concentration via metabolism of non-classical or classical ketogenic precursors. Classical ketogenesis itself may drive adaptation and some of the functional benefits associated with ketosis. BDO is included in all of the KE compounds, but it is currently unknown how consumption of BDO alone, and its metabolism via non-classical ketogenesis acutely affects metabolism. Additionally, ketogenesis is now understood to occur in certain cells outside the liver with important local biological effects, for example ketogenesis driven by medium chain fatty acids has been reported in astrocytes in vitro. Provision of systemic BHB by a KE may elicit different biological effects in some tissues such as the brain versus promoting in situ ketogenesis in that tissue. Overall, not only are functional effects of KE incompletely defined, but also it is unknown which effects are common to all KE versus which are specific to an individual KE compound (i.e., BHB Monoester vs AcAc Diester) or which may be attributable to the BDO precursor common to all of the KE. This study will be the first comparative full crossover study of all available KE and the precursor BDO at two serving sizes. Outcomes will focus on established effects of the BHB Monoester (including the effects on ketones, glucose and acid-base balance) and compare these with the effects of the AcAc Diester, C8 Ketonef Diester and BDO.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

BHB Monoester, C8 Diester, and (R) 1,3 Butanediol are commercially available in the products 'deltaG' (TdeltaS Global, FL, USA), 'Cognitive Switch' (Juvenescence Ltd, NJ, USA) and 'Avela' (Genomatica, CA, USA), respectively. The AcAc Diester is commercially available and is currently being used in clinical studies of Angelman's Disease. Therefore, we will standardize KE dosing to LBM (assessed using DXA) for all trials at 180 and 360 mg/kg LBM, which for a participant with 70 kg of lean mass corresponds to ~12.5 and 25 g, respectively. These doses are representative of typical commercial serving sizes and are expected to elevate blood BHB in the range of 1.5 - 2 mM39,61. All KEs will be consumed in their finished commercial form. As the KEs have different delivery matrices and flavorings (water-based beverage, emulsion beverage, gel capsules), we will not blind participants to each condition as this will not alter the metabolic outcomes of interest. Screening Visit: Participants that meet the initial qualifying criteria will visit the study center for a screening meeting in a private office to discuss the informed consent form with research team. The informed consent form will be provided to the participant for their review, the study will be described in full detail and any questions the interested participant has will be encouraged and responded to. The participant will be informed that even if they have signed the consent form, their participation in the study is dependent on anthropometric measures and diet and medical questionnaire answers to determine if they meet the study criteria. If the participant provides consent, they will be provided with questionnaires including Automated Self-administered 24-hour Dietary Assessment Tool (ASA24®),and medical history. All collected samples and data will be coded to maintain participant anonymity. We will give the participants a small volume of Study Product to screen for tolerance of the bitter tasting Study Products. We will also measure height, weight, BMI and body composition using a DXA scanner. If the participant is eligible for the study and is still interested in participating then they will be randomized to a study product order and scheduled to return to the study center for the first testing visit. Eligible participants will report to the study center in compliance with pre-test instructions (fasted > 10h, no alcohol >24h, no exercise >24h, consumed pre-test food). Upon testing day, participants will complete a baseline Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale. Participants will be asked to completely void their bladder and a sample will be analyzed for hydration status. Bluetooth heart rate monitor chest strap will be administered. A study team member will assist the participant with application of a continuous ketone meter into the back of the arm, this will be removed and replaced with a fresh sensor at Test Days at ~2-week intervals; the sensor will be removed 24 hours after the cessation of the last in lab testing bout. Participants will be given written instructions on how to remove and dispose of monitor. A trained member of the study team will insert an IV cannula into a vein in the antecubital fossa to allow for repeated blood sampling. The cannula will be flushed with a small volume of saline after each sample withdrawal to maintain patency. We will collect 56mL of blood (7 x 8mL tubes) per testing day, which will be about 504mL of blood for the entire study. This is about 2.1 cups of blood. We will also collect capillary blood samples from a finger for real-time analysis of blood BHB and glucose concentration, using lancing device, commercially available test strips and a handheld monitor (KetoMojo, CA, USA). Participants will wear a fitted facemask connected to a metabolic cart for 10 minutes to collect measures of respiratory gas exchange. Participants will exhale once into a commercially available handheld breath acetone analyzer (Readout, MI, USA). Baseline blood sample, baseline respiratory gas measures and baseline breath acetone will be collected. Participants will then consume the Study Product that they were randomly allocated for that Test Day (details of Study Products attached in other files). Time of ingestion should be +/- 60 minutes from the time established at Test Day 1; they will be given 5 minutes to consume the Product. After Study Product consumption, they will remain at the study center for ~4 hours, repeating the aforementioned tests at 30min, 60 min, 90min, 180min & 240min. Participants will be asked to minimize ambulatory movement during the Test Day. Non caloric beverages (i.e.,water) will be permitted ad libitum and intake volumes will be recorded. At the end of each Test Day, the heart rate monitor and IV cannula will be removed and a dressing will be applied to the cannula site. Participants will be given a snack to consume before leaving the site.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 30 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Male
  • BMI between 18 and 29 kg/m2
  • Aged 20 - 30 years
  • Participant is willing and able to comply with all study procedures including the following prior to Test Days: fasting (>10 h; water only), no alcohol (>24 h), no exercise (>24 h), no acute illness and controlled feeding before each Test Day, maintain diet, exercise, medication, and supplement habits throughout the study.
  • Participant has no health conditions that would prevent completion of the study requirements as judged by the Investigator based on health history.
  • Participant understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Investigator.

Exclusion Criteria:

  • Participant follows a low-carbohydrate diet (<30% energy from carbohydrate) or have used exogenous ketone supplements within 4-months of study participation.
  • Participant has a Primary Care Physician diagnosed history or presence of uncontrolled and/or clinically important hypertension (blood pressure >150/95 mmHg), pulmonary, cardiac, hepatic, renal, endocrine (including type 1 and 2 diabetes), hematologic, immunologic, neurologic (e.g., Alzheimer's or Parkinson's diseases), psychiatric (including unstable depression and/or anxiety disorders) or biliary disorders.
  • Participant has a known allergy, intolerance, or sensitivity to any of the ingredients in the study beverages, including soy and milk protein, wheat, shellfish, fin fish, eggs, tree nuts or peanuts (production facility handles nuts).
  • Participant has unstable use of a medication or supplement that the Investigator considers may affect the outcomes of the trial.
  • Consumption of alcohol more than 3 drinks per day or more than 18 drinks per week.
  • Consumption of tobacco.
  • Consumption of cannabis.
  • Participant is currently in another research study or has been in the 14 days before screening.
  • Participant has had a blood draw or donation in the last 8 weeks.
  • Participant has a clinically important gastrointestinal (GI) condition that would potentially interfere with the evaluation of the study beverage [e.g., inflammatory bowel disease, irritable bowel syndrome, chronic constipation, severe constipation (in the opinion of the Investigator), history of frequent diarrhea, history of surgery for weight loss, gastroparesis, systemic disease that might affect gut motility according to the Investigator, medication managed reflux and/or clinically important lactose intolerance].
  • Participant has a condition the Investigator believes would interfere with his ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results, or put the participant at undue risk.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Control
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Radiation: DXA
Lean Body Mass will be assessed once via DXA
Experimental: BHB Mono-ester 180mg/kg
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Experimental: BHB mono-ester 360mg/kg
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Experimental: AcAc Di-ester 180mg/kg
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Experimental: AcAc Di-ester 360mg/kg
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Experimental: (R)-1,3 butanediol 180mg/kg
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Experimental: (R)-1,3 butanediol 360mg/kg
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Experimental: C8 Ketone Di-ester 180mg/kg
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis
Experimental: C8 Ketone Di-ester 360mg/kg
Dietary supplement: Ketone Supplement
Four different exogenous ketone products at two serving sizes or a non-ketogenic placebo (one study product per test day). 1) Monoester of BHB (R)-1,3 butanediol (BHB Mono-ester), 2) diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) 3) diester of AcAc and (R,S)-1,3 butanediol (AcAc Di-ester) & 4) (R) -1,3 butanediol only (BDO). All products will be delivered in 2 different dosages 180mg/kg and 360mg/kg on separate testing days.
Behavioral: Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale
Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale will be administered at beginning and end of testing day to tests palatability of supplement
Biological: Blood Draw
IV cannula will be inserted at the start of each Test Day, and removed at the end of each Test Day, Blood samples will be collected according to the schedule in Figure 1. Cannula will be flushed with a small volume of saline after each sample to maintain patency. We will draw 504 mL of blood, which is about 2.1 cups throughout the 4-week intervention
Other: Breath Reading
Participants will breathe into a commercially available handheld breath acetone analyzer according to the schedule. Participants will wear a fitted face mask attached to a metabolic cart for a 10-minute period every 60 minutes
Other: Heart Rate Variability
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day.
Other: CGM/CKM
Continuous Ketone Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day
Other: Urine Analysis
Prior to consumption of the Study Product, participants will be asked to completely void bladder. And hydration status will be determined via urine specific gravity (USG) reporting <1.025. Urine passed after the ingestion of the study product will be collected in a plastic container; participants will be asked to void their bladder and collect urine at the end of the test day. The volume produced will be recorded at the end of the study and aliquots will be frozen and stored for future analysis

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Total Plasma Ketone AUC
Time Frame: Up to ~ 4 weeks
Difference in total plasma ketone appearance (AUC) between the two serving sizes of study products and control
Up to ~ 4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Insulin
Time Frame: Up to ~ 4 weeks
Differences in blood hormones insulin after supplementation will be analyzed using commercially available ELISA assay kits (Cayman Chemical, USA).
Up to ~ 4 weeks
Capillary d-BHB concentrations
Time Frame: Up to ~ 4 weeks
Differences in ketone appearance during testing days
Up to ~ 4 weeks
AcAc, R-BHB and S-BHB changes across trials
Time Frame: Up to ~ 4 weeks
Differences in other blood ketones between the two serving sizes of study products and control. This will allow us to deduce specific ketone bodies during intervention.
Up to ~ 4 weeks
Continuous Ketone and Glucose Monitoring
Time Frame: Up to ~ 4 weeks
Diurnal concentrations of ketones and glucose via a continuous monitor. The ketone sensor in this CKM device is similar to the FreeStyle Libre continuous glucose monitoring (CGM). The sensor adheres to the back of the arm where it continuously samples interstitial fluid for quantification of BHB concentration. The sensor is worn for a period of 2-wk, three sensors will be used to cover all test days in this study (6 weeks). The first sensor will be inserted with assistance from the study team at the start of Testy Day 1, it will be checked every visit and replaced at Test Days following ~2-week intervals. The sensor will be removed 24 hours after the cessation of the last in lab testing bout (Testing Day 9). Participants will be given written instructions on how to remove and dispose of monitor. Feasibility, stability and other quality control parameters of this CKM/CGM has been established.
Up to ~ 4 weeks
Ketone Excretion
Time Frame: Up to ~ 4 weeks
Changes in urine excretion analysis
Up to ~ 4 weeks
Ketone in breathe expiration
Time Frame: Up to ~ 4 weeks
Concentration in breathe acetone via hand held reader
Up to ~ 4 weeks
Alanine Change
Time Frame: Up to ~ 4 weeks
Concentrations in blood metabolites will be determined using standard enzymatic assays.
Up to ~ 4 weeks
Lactate Change
Time Frame: Up to ~ 4 weeks
Concentrations in blood metabolites will be determined using standard enzymatic assays.
Up to ~ 4 weeks
Free Fatty Acid Change
Time Frame: Up to ~ 4 weeks
Concentrations in blood metabolites will be determined using standard enzymatic assays.
Up to ~ 4 weeks
Heart Rate Variability
Time Frame: Up to ~ 4 weeks
Changes in heart rate and heart rate variability
Up to ~ 4 weeks
Satiety Visual Analogue Scale
Time Frame: Up to ~ 4 weeks
We will use a 3-item visual analogue scale, that assesses hunger, fullness and desire to eat by participant's marking on a line anchored at either end with 'not at all' and 'extremely.' Distance along the line is measured in mm.
Up to ~ 4 weeks
Beverage tolerability questionnaire (BTQ)
Time Frame: Up to ~ 4 weeks
Ten tolerability issues are included in the BTQ: gas/flatulence, nausea, vomiting, abdominal cramping, stomach rumbling, burping, reflux (heartburn), diarrhea, headache, and dizziness. Participants are asked if the issue was present (pre- beverage - baseline) or had occurred since they took the study beverage (post-beverage - 4h) at the following intensities: none, mild (awareness of symptoms but easily tolerated), moderate (discomfort enough to interfere with but not prevent daily activity) or severe (unable to perform usual activity). These correspond to scores of 0-3, respectively for each issue, giving a maximal composite score, defined as the sum of the ten items, of 30.
Up to ~ 4 weeks
Ghrelin
Time Frame: Up to ~ 4 weeks
Differences in blood hormones ghrelin after supplementation will be analyzed using commercially available ELISA assay kits (Cayman Chemical, USA).
Up to ~ 4 weeks
Acid-Base Balance
Time Frame: Up to ~ 4 weeks
Differences in blood acid-base balance (bicarbonate, strong ions)
Up to ~ 4 weeks
Respiratory Gas Exchange
Time Frame: Up to ~ 4 weeks
Differences in respiratory gas exchange (VO2 and VCO2)
Up to ~ 4 weeks
Whole blood clinical chemistry
Time Frame: Up to ~ 4 weeks
Whole blood clinical chemistry will be performed using a commercially available, clinical grade handheld analyzer (iSTAT, Abott, USA) and cartridges which will deliver the following data: Sodium, Potassium, pH, PCO2, Urea Nitrogen, Glucose, Hematocrit, TCO2, HCO3, Base Excess, Anion Gap, Hemoglobin (EC8+, Abott, USA).
Up to ~ 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ohio State University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jeff S Volek, PhD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 5, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 1, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 11, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 15, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2022H0160
  • CDMRP-PR212399-A (Other Grant/Funding Number: Departentof Defense)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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