KetosisNCT04737694
Ketone Supplements and Substrate Oxidation and Physical Performance
A study testing Ketone ester and Glucose in people with Ketosis and Glucose Metabolism, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
Trial summary
The objective of this randomized crossover study is to examine the influence of consuming a ketone ester plus carbohydrate (KE+CHO) supplement on substrate oxidation and physical performance in 15 healthy adults. Read more about this study
- Who is it for?
- Ages 18 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Ketosis, Glucose Metabolism
- What is being tested?
- Ketone ester and Glucose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2020to 1 Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women aged 18 - 39 years
- Body mass index (BMI) < 30 kg/m2
- Routinely participate in aerobic and/or resistance exercise at least 2 days per week
- Refrain from the use of caffeine, alcohol, dietary supplements, and nicotine while consuming study diets
- Supervisor approval to participate for active duty military and federal civilian employees working within the US Army Natick Soldier Systems Center
Who cannot join
- Metabolic or cardiovascular abnormalities, gastrointestinal disorders (i.e., kidney disease, diabetes, cardiovascular disease, etc.)
- Disease or medication (i.e., diabetes medications, statins, corticosteroids, etc) that affects macronutrient utilization and/or the ability to participate in strenuous exercise
- Allergies or intolerance to foods (including but not limited to lactose intolerance/milk allergy) to be utilized in the study or vegetarian practices
- Present condition of alcoholism, anabolic steroids, or other substance abuse issues
- Musculoskeletal injuries that compromise the ability to exercise
- Not willing to avoid non-study exercise and foods during each of the 3 day testing periods
- Blood donation within 8 weeks of beginning the study
- Pregnant or breast feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Ketone Ester Supplementation on Substrate Oxidation and Physical Performance
The objective of this randomized crossover study is to examine the influence of consuming a ketone ester plus carbohydrate (KE+CHO) supplement on substrate oxidation and physical performance in 15 healthy adults. Following a 48-hr muscle glycogen normalization period, volunteers will consume either an isocaloric KE+CHO (KE: 573 mg KE/kg body mass, CHO: 110 g) or isocaloric CHO drink and complete 90-min of metabolically-matched, load carriage (~30% body mass) steady-state aerobic (~60 ± 5 % of VO2peak) exercise on a treadmill. Glucose tracers will be used to assess glucose turnover, and contribution to exogenous and plasma glucose oxidation. Serial blood draws will be collected during each trial to assess endocrine and circulating substrate responses. After steady-state exercise volunteers will complete a time to exhaustion (TTE) physical performance tests at 85% VO2peak on a treadmill. Volunteers will then be provided with food for the remainder of the day. Following a 10-hr overnight fast, volunteers will return to the laboratory and consume the same supplement (KE+CHO or CHO) as they did the previous day. Volunteers will then perform a 4-mile load carriage time trial on a treadmill. Following a minimum 7-day washout period, volunteers will return to the laboratory to complete the second arm of the study. The primary risks associated with this study include those associated with exercise, blood draws, and gastrointestinal discomfort from the KE+CHO supplement.
Read the detailed description
Following an overnight (10 hour) fast, two catheters will be placed into the lower arm (one in each arm). One arm will be used for infusion of 6,6-[2H2] glucose tracer and the other will be used for blood sampling under resting and exercise conditions. Following an initial blood sample collection to determine background enrichments, a primed, continuous infusion of 6,6-[2H2] glucose will begin (prime, 82.2 µmol∙kg-1; continuous rate, 0.78 µmol∙kg-1∙min-1, Figure 1). The 6,6-[2H2] glucose will be infused for 100 min under resting fasted conditions to ensure isotopic steady-state is achieved prior to initiating exercise. Volunteers will consume either an isocaloric KE+CHO (KE: 573 mg KE/kg body mass, CHO: 110 g) or CHO drink prior to and during 90-min of metabolically-matched (~60 ± 5 % of VO2peak), steady-state load carriage (~30% body mass) exercise. Drinks will be enriched with U-13C-glucose (Cambridge Isotope Laboratory, Andover, MA, USA) to increase the isotopic enrichment well above natural levels and optimize the measurement of exogenous carbohydrate oxidation. During exercise V̇O2, V̇CO2, and HR will be measured at approximately 0, 20, 45, 60, 75, and 85 min.
After the 90-min steady-state treadmill exercise, participants will complete a TTE performance test. For volunteer safety TTE performance tests will be conducted without the additional weight from the load carriage exercise. Volunteers will be given time to stretch and warm-up on the treadmill before the TTE performance test beings. Volunteers will then run on the treadmill at a fixed speed and grade that elicits 85% of their VO2peak. The TTE performance test will be determined as the time of volitional exhaustion. Following completion of the test, a self-selected cool-down will occur. Volunteers will complete a minimum of two practice exercise sessions to ensure they are familiar with the performance test.
The following day volunteers will return to the laboratory after an overnight fast. After consuming the study drink (KE+CHO or CHO) participants will complete a self-paced 4-mile load carriage (~30% body mass) time trial on a treadmill to assess aerobic performance. Time trial performance will be assessed as the total amount of time taken to complete 4 miles. The treadmill will be set at a constant 1% grade for the entire test. Following a warm-up period, volunteers will blindly modulate treadmill speed in order to complete the distance as quickly as possible. The only feedback given will be distance covered at half mile increments. At half mile increments volunteers' rate of perceived exertion will be determined using the Borg Scale. Heart rate will be monitored throughout the time trial. Heart rate will be recorded at half mile increments. No motivation will be provided during the time trial. Participants may consume water ad libitum during the time trial. Following completion of the test, a self-selected cool-down will occur. Volunteers will complete a minimum of two practice exercise sessions to ensure they are familiar with the performance test.
- Conditions
- Ketosis, Glucose Metabolism
- Being tested
- Ketone ester, Glucose
- Medical subject headings
- Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone esterDietary supplement
Oral ketone ester + glucose supplement
GlucoseDietary supplement
Glucose supplement
| Study group | Role | What they receive |
|---|---|---|
| Ketone + Carbohydrate | Experimental | 573 mg/ kg body weight ketone ester + 110 g glucose Receives: Dietary Supplement: Ketone ester |
| Carbohydrate | Active comparator | Isocaloric amount of glucose to match ketone + carbohydrate Receives: Dietary Supplement: Glucose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to exhaustion
Determine the effect of ketone esters plus carbohydrate (KE + CHO) supplementation on physical performance as determine by time to exhaustion at 85% VO2max on a treadmill compared to CHO alone
Measured: 30 minutes
Time trial
Determine the effect of ketone esters plus carbohydrate (KE + CHO) supplementation on physical performance as determine by a self paced 4 mile time trial on a treadmill compared to CHO alone
Measured: 120 minutes
Substrate oxidatoin
Determine the effect of KE + CHO supplementation on changes in substrate oxidation during moderate-intensity load carriage exercise compared to CHO alone.
Measured: 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2021
- Study start1 Nov 2020
- Primary completion1 Jun 2021
- Study completion1 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for KetosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double blinded randomized crossover design
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- United States Army Research Institute of Environmental Medicine
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Lee M Margolis, PhD, Principal investigator, United States Army Research Institute of Environmental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04737694
- Sponsor's protocol ID
- 20-07HC
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 2020
- Last updated
- 14 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Howard EE, Allen JT, Coleman JL, Small SD, Karl JP, O'Fallon KS, Margolis LM. Ketone Monoester Plus Carbohydrate Supplementation Does Not Alter Exogenous and Plasma Glucose Oxidation or Metabolic Clearance Rate During Exercise in Men Compared with Carbohydrate Alone. J Nutr. 2023 Jun;153(6):1696-1709. doi: 10.1016/j.tjnut.2023.03.002. Epub 2023 Mar 8.
PubMed 36893935
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Ketone Ester Supplementation on Substrate Oxidation and Physical Performance
- ClinicalTrials.gov ID
- NCT04737694
- Acronym / sponsor ID
- 20-07HC
- Conditions
- Ketosis, Glucose Metabolism
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (actual)
- Lead sponsor
- United States Army Research Institute of Environmental MedicineUS federal agency
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Sep 2022 (estimated)
- First posted
- 4 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this randomized crossover study is to examine the influence of consuming a ketone ester plus carbohydrate (KE+CHO) supplement on substrate oxidation and physical performance in 15 healthy adults. Following a 48-hr muscle glycogen normalization period, volunteers will consume either an isocaloric KE+CHO (KE: 573 mg KE/kg body mass, CHO: 110 g) or isocaloric CHO drink and complete 90-min of metabolically-matched, load carriage (~30% body mass) steady-state aerobic (~60 ± 5 % of VO2peak) exercise on a treadmill. Glucose tracers will be used to assess glucose turnover, and contribution to exogenous and plasma glucose oxidation. Serial blood draws will be collected during each trial to assess endocrine and circulating substrate responses. After steady-state exercise volunteers will complete a time to exhaustion (TTE) physical performance tests at 85% VO2peak on a treadmill. Volunteers will then be provided with food for the remainder of the day. Following a 10-hr overnight fast, volunteers will return to the laboratory and consume the same supplement (KE+CHO or CHO) as they did the previous day. Volunteers will then perform a 4-mile load carriage time trial on a treadmill. Following a minimum 7-day washout period, volunteers will return to the laboratory to complete the second arm of the study. The primary risks associated with this study include those associated with exercise, blood draws, and gastrointestinal discomfort from the KE+CHO supplement.
Detailed description
Following an overnight (10 hour) fast, two catheters will be placed into the lower arm (one in each arm). One arm will be used for infusion of 6,6-[2H2] glucose tracer and the other will be used for blood sampling under resting and exercise conditions. Following an initial blood sample collection to determine background enrichments, a primed, continuous infusion of 6,6-[2H2] glucose will begin (prime, 82.2 µmol∙kg-1; continuous rate, 0.78 µmol∙kg-1∙min-1, Figure 1). The 6,6-[2H2] glucose will be infused for 100 min under resting fasted conditions to ensure isotopic steady-state is achieved prior to initiating exercise. Volunteers will consume either an isocaloric KE+CHO (KE: 573 mg KE/kg body mass, CHO: 110 g) or CHO drink prior to and during 90-min of metabolically-matched (~60 ± 5 % of VO2peak), steady-state load carriage (~30% body mass) exercise. Drinks will be enriched with U-13C-glucose (Cambridge Isotope Laboratory, Andover, MA, USA) to increase the isotopic enrichment well above natural levels and optimize the measurement of exogenous carbohydrate oxidation. During exercise V̇O2, V̇CO2, and HR will be measured at approximately 0, 20, 45, 60, 75, and 85 min.
After the 90-min steady-state treadmill exercise, participants will complete a TTE performance test. For volunteer safety TTE performance tests will be conducted without the additional weight from the load carriage exercise. Volunteers will be given time to stretch and warm-up on the treadmill before the TTE performance test beings. Volunteers will then run on the treadmill at a fixed speed and grade that elicits 85% of their VO2peak. The TTE performance test will be determined as the time of volitional exhaustion. Following completion of the test, a self-selected cool-down will occur. Volunteers will complete a minimum of two practice exercise sessions to ensure they are familiar with the performance test.
The following day volunteers will return to the laboratory after an overnight fast. After consuming the study drink (KE+CHO or CHO) participants will complete a self-paced 4-mile load carriage (~30% body mass) time trial on a treadmill to assess aerobic performance. Time trial performance will be assessed as the total amount of time taken to complete 4 miles. The treadmill will be set at a constant 1% grade for the entire test. Following a warm-up period, volunteers will blindly modulate treadmill speed in order to complete the distance as quickly as possible. The only feedback given will be distance covered at half mile increments. At half mile increments volunteers' rate of perceived exertion will be determined using the Borg Scale. Heart rate will be monitored throughout the time trial. Heart rate will be recorded at half mile increments. No motivation will be provided during the time trial. Participants may consume water ad libitum during the time trial. Following completion of the test, a self-selected cool-down will occur. Volunteers will complete a minimum of two practice exercise sessions to ensure they are familiar with the performance test.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double blinded randomized crossover design
| Arm | Type | Receives |
|---|---|---|
| Ketone + Carbohydrate | Experimental | Dietary Supplement: Ketone ester573 mg/ kg body weight ketone ester + 110 g glucose |
| Carbohydrate | Active comparator | Dietary Supplement: GlucoseIsocaloric amount of glucose to match ketone + carbohydrate |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Men and women aged 18 - 39 years
- Body mass index (BMI) < 30 kg/m2
- Routinely participate in aerobic and/or resistance exercise at least 2 days per week
- Refrain from the use of caffeine, alcohol, dietary supplements, and nicotine while consuming study diets
- Supervisor approval to participate for active duty military and federal civilian employees working within the US Army Natick Soldier Systems Center
Key exclusion criteria (8 listed)
- Metabolic or cardiovascular abnormalities, gastrointestinal disorders (i.e., kidney disease, diabetes, cardiovascular disease, etc.)
- Disease or medication (i.e., diabetes medications, statins, corticosteroids, etc) that affects macronutrient utilization and/or the ability to participate in strenuous exercise
- Allergies or intolerance to foods (including but not limited to lactose intolerance/milk allergy) to be utilized in the study or vegetarian practices
- Present condition of alcoholism, anabolic steroids, or other substance abuse issues
- Musculoskeletal injuries that compromise the ability to exercise
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketone esterOral ketone ester + glucose supplement | Dietary supplement | Ketone + Carbohydrate |
| GlucoseGlucose supplement | Dietary supplement | Carbohydrate |
Primary outcome
Time to exhaustion
Time frame: 30 minutes
Determine the effect of ketone esters plus carbohydrate (KE + CHO) supplementation on physical performance as determine by time to exhaustion at 85% VO2max on a treadmill compared to CHO alone
Time trial
Time frame: 120 minutes
Determine the effect of ketone esters plus carbohydrate (KE + CHO) supplementation on physical performance as determine by a self paced 4 mile time trial on a treadmill compared to CHO alone
Substrate oxidatoin
Time frame: 90 minutes
Determine the effect of KE + CHO supplementation on changes in substrate oxidation during moderate-intensity load carriage exercise compared to CHO alone.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2021.
- Derived from this study: PubMed 36893935Howard EE, Allen JT, Coleman JL, Small SD, Karl JP, O'Fallon KS, Margolis LM. Ketone Monoester Plus Carbohydrate Supplementation Does Not Alter Exogenous and Plasma Glucose Oxidation or Metabolic Clearance Rate During Exercise in Men Compared with Carbohydrate Alone. J Nutr. 2023 Jun;153(6):1696-1709. doi: 10.1016/j.tjnut.2023.03.002. Epub 2023 Mar 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee M Margolis, PhD principal investigator
United States Army Research Institute of Environmental Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone ester and Glucose in people with Ketosis and Glucose Metabolism, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to exhaustion (time frame: 30 minutes). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04737694, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2021.