Exercise PhysiologyNCT07854223
Effects of Pre-Run Nutritional Supplements During a Fixed-Pace 5 km Treadmill Run
A study testing Caffeine, L-Citrulline and Exogenous Ketone (Beta-Hydroxybutyrate) in people with Exercise Physiology and Nutritional Supplementation, run by St. Louis University at 1 site in United States.
Trial summary
This study will examine how three commonly used pre-run nutritional supplements-caffeine, L-citrulline, and an exogenous ketone supplement-affect physiological and perceptual responses during a fixed-pace 5 km treadmill run in healthy, physically active runners. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Exercise Physiology, Nutritional Supplementation
- What is being tested?
- Caffeine, L-Citrulline and Exogenous Ketone (Beta-Hydroxybutyrate)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2026to Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-35 years
- Healthy adult
- Able to provide written informed consent
- Regularly engaged in running-based aerobic training at least 3 times per week for at least 30 minutes per session during the past 3 months
- Able to complete a 5 km run in under 30 minutes
- Able and willing to comply with treadmill testing, fingerstick testing, dietary standardization, supplement restrictions, and pre-visit instructions
- Participants randomly selected for the continuous glucose monitoring subgroup must also be willing to undergo Dexcom Stelo continuous glucose monitor placement and wear
Who cannot join
- Known cardiovascular, metabolic, pulmonary, or neurological disease that may increase the risk associated with exercise testing or materially influence study outcomes
- Uncontrolled hypertension or another cardiovascular condition that, in the investigator's judgment, makes vigorous treadmill exercise unsafe
- Diagnosed type 1 or type 2 diabetes mellitus or another known metabolic disease that may materially influence study outcomes
- Pregnant, breastfeeding, or planning pregnancy during the study period
- Current use of nitrate medications or phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil, tadalafil, or vardenafil
- Known sensitivity or allergy to caffeine, L-citrulline, exogenous ketone/BHB salt products, or any study beverage ingredient
Show all 12Show fewer
- Current use of stimulant medications or other medications that may significantly influence cardiovascular, blood pressure, or metabolic responses to exercise, as determined by the investigator
- Musculoskeletal injury or condition that limits safe treadmill running
- Smoking or regular use of nicotine products
- Recent illness, surgery, or hospitalization that, in the opinion of the investigators, may interfere with safe participation or study outcomes
- Unable or unwilling to comply with study procedures or pre-visit standardization requirements
- Running fewer than 3 times per week or otherwise not meeting the running-training inclusion criterion
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Saint Louis University, Allied Health Building
St Louis, Missouri, 63104
Hossein Rafiei, PhD RD, 314-977-8675, hossein.rafiei@health.slu.edu
hossein.rafiei@health.slu.edu
About this study
Official title: Fueling the Kilometers: Effects of Pre-Run Nutritional Supplements on Physiological Responses During a Fixed-Pace 5 km Treadmill Run
This study will examine how three commonly used pre-run nutritional supplements-caffeine, L-citrulline, and an exogenous ketone supplement-affect physiological and perceptual responses during a fixed-pace 5 km treadmill run in healthy, physically active runners.
Participants will complete one screening and baseline visit followed by four experimental visits in a randomized order. At each experimental visit, participants will receive caffeine, L-citrulline, an exogenous ketone supplement, or placebo before completing a fixed-pace 5 km treadmill run. Each participant will receive all four conditions and will therefore serve as their own control.
The study will evaluate measures including running economy, heart-rate responses, oxygen consumption, respiratory measures, blood lactate and ketone concentrations, perceived exertion, gastrointestinal symptoms, fatigue, energy, and focus. A randomly selected subgroup will also wear a continuous glucose monitor to explore glucose responses during the experimental visits. The study will also assess the feasibility and tolerability of completing repeated treadmill trials under the four supplement conditions.
Read the detailed description
This is a randomized, single-blind, placebo-controlled crossover study designed to compare acute physiological and perceptual responses to three pre-run nutritional supplements and placebo during a controlled fixed-pace 5 km treadmill run. Healthy, physically active runners will complete one screening/baseline visit and four experimental visits. Each participant will complete all four experimental conditions in randomized order and will serve as their own control. A minimum washout/recovery period of four days will separate experimental visits.
At each experimental visit, participants will receive one of four pre-run conditions: caffeine at 4 mg/kg body weight, L-citrulline at 7 g, an exogenous ketone supplement providing 11.5 g beta-hydroxybutyrate (BHB), or placebo. Study products will be provided in a standardized beverage vehicle, followed by a 45-minute waiting period before the treadmill run.
The primary physiological outcomes of interest are running economy and heart-rate drift during the fixed-pace 5 km treadmill run. Additional outcomes include oxygen consumption, carbon dioxide production, ventilation, respiratory exchange ratio, heart-rate recovery, capillary blood lactate and ketone concentrations, rating of perceived exertion, gastrointestinal symptoms, subjective fatigue, energy, focus, and participant-reported perceptions of the assigned supplement condition.
A prespecified randomly selected subgroup of up to 12 enrolled participants will use a Dexcom Stelo continuous glucose monitor during the experimental phase. CGM-derived glucose responses will be analyzed as exploratory outcomes within this subgroup only.
The study will also evaluate feasibility and tolerability, including visit completion, adverse events, supplement-related symptoms, gastrointestinal symptoms, and completeness of study measurements. The results are intended to characterize within-participant differences among the four conditions and provide preliminary data for future confirmatory studies.
- Conditions
- Exercise Physiology, Nutritional Supplementation
- Being tested
- Caffeine, L-Citrulline, Exogenous Ketone (Beta-Hydroxybutyrate), placebo beverage
- Keywords
- Running Economy, Heart Rate Drift, Caffeine, L-Citrulline, Exogenous Ketones, Beta-Hydroxybutyrate, 5 km Running, Endurance Exercise, Nutritional Supplements, Indirect Calorimetry, Blood Lactate, Blood Ketones, Continuous Glucose Monitoring
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDietary supplement
Caffeine will be administered at exactly 4 mg/kg body weight. The individualized dose will be calculated using body weight measured at the baseline visit. The commercially manufactured capsule contents will be weighed by trained study staff using a calibrated analytical balance to obtain the protocol-specified dose. Caffeine will be dispensed in the standardized study beverage and consumed 45 minutes before the fixed-pace 5 km treadmill run.
L-CitrullineDietary supplement
L-citrulline will be administered at exactly 7.0 g. The commercially manufactured pure L-citrulline powder will be weighed using a calibrated analytical balance, dispensed in the standardized study beverage, and consumed 45 minutes before the fixed-pace 5 km treadmill run.
Exogenous Ketone (Beta-Hydroxybutyrate)Dietary supplement
The exogenous ketone condition will consist of one 15 g serving of Nutricost Ketone BHB Salt 4-in-1 Powder, providing 11.5 g beta-hydroxybutyrate (BHB) as calcium, magnesium, sodium, and potassium BHB salts. The supplement will be dispensed in the standardized study beverage and consumed 45 minutes before the fixed-pace 5 km treadmill run.
placebo beverageOther
The placebo will be a study-prepared beverage containing water, food-grade lime flavoring, and stevia, with no active study supplement. It will use the same standardized final volume as the active conditions and will be consumed 45 minutes before the fixed-pace 5 km treadmill run.
| Study group | Role | What they receive |
|---|---|---|
| Sequence 1: Caffeine-L-Citrulline-Placebo-Ketone | Experimental | Participants assigned to this randomized crossover sequence will receive caffeine, followed by L-citrulline, placebo, and exogenous ketone across four experimental visits. Each intervention will be administered 45 minutes before a fixed-pace 5 km treadmill run. Experimental visits will be separated by a minimum washout/recovery period of four days. Receives: Dietary Supplement: Caffeine; Dietary Supplement: L-Citrulline; Dietary Supplement: Exogenous Ketone (Beta-Hydroxybutyrate); Other: placebo beverage |
| Sequence 2: L-Citrulline-Ketone-Caffeine-Placebo | Experimental | Participants assigned to this randomized crossover sequence will receive L-citrulline, followed by exogenous ketone, caffeine, and placebo across four experimental visits. Each intervention will be administered 45 minutes before a fixed-pace 5 km treadmill run. Experimental visits will be separated by a minimum washout/recovery period of four days. Receives: Dietary Supplement: Caffeine; Dietary Supplement: L-Citrulline; Dietary Supplement: Exogenous Ketone (Beta-Hydroxybutyrate); Other: placebo beverage |
| Sequence 3: Ketone-Placebo-L-Citrulline-Caffeine | Experimental | Participants assigned to this randomized crossover sequence will receive exogenous ketone, followed by placebo, L-citrulline, and caffeine across four experimental visits. Each intervention will be administered 45 minutes before a fixed-pace 5 km treadmill run. Experimental visits will be separated by a minimum washout/recovery period of four days. Receives: Dietary Supplement: Caffeine; Dietary Supplement: L-Citrulline; Dietary Supplement: Exogenous Ketone (Beta-Hydroxybutyrate); Other: placebo beverage |
| Sequence 4: Placebo-Caffeine-Ketone-L-Citrulline | Experimental | Participants assigned to this randomized crossover sequence will receive placebo, followed by caffeine, exogenous ketone, and L-citrulline across four experimental visits. Each intervention will be administered 45 minutes before a fixed-pace 5 km treadmill run. Experimental visits will be separated by a minimum washout/recovery period of four days. Receives: Dietary Supplement: Caffeine; Dietary Supplement: L-Citrulline; Dietary Supplement: Exogenous Ketone (Beta-Hydroxybutyrate); Other: placebo beverage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Running Economy (VO₂) During the Fixed-Pace 5 km Treadmill Run
Running economy will be assessed using oxygen consumption (VO₂) measured by indirect calorimetry during standardized portions of the fixed-pace 5 km treadmill run. Within-participant running-economy responses will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Measured: During the fixed-pace 5 km treadmill run at each of the four experimental visits, approximately 45 minutes after supplement/placebo ingestion.
Heart-Rate Drift During the Fixed-Pace 5 km Treadmill Run
Heart-rate drift will be assessed from continuous heart-rate monitoring as the change in heart rate over the course of the fixed-pace 5 km treadmill run. Within-participant heart-rate drift will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Measured: Throughout the fixed-pace 5 km treadmill run at each of the four experimental visits, approximately 45 minutes after supplement/placebo ingestion.
Secondary outcomes (13)
Mean Oxygen Consumption (VO₂) During the Fixed-Pace 5 km Treadmill Run
Oxygen consumption (VO₂) will be measured continuously by indirect calorimetry and summarized as the mean body-mass-normalized VO₂ (mL/kg/min) during the fixed-pace 5 km treadmill run. Within-participant mean VO₂ will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Measured: During the fixed-pace 5 km treadmill run at each of the four experimental visits, beginning approximately 45 minutes after supplement/placebo ingestion.
Mean Carbon Dioxide Production (VCO₂) During the Fixed-Pace 5 km Treadmill Run
Carbon dioxide production (VCO₂) will be measured continuously by indirect calorimetry and summarized as the mean VCO₂ (L/min) during the fixed-pace 5 km treadmill run. Within-participant mean VCO₂ will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Measured: During the fixed-pace 5 km treadmill run at each of the four experimental visits, beginning approximately 45 minutes after supplement/placebo ingestion.
Ventilation
Pulmonary ventilation will be measured using indirect calorimetry during the fixed-pace 5 km treadmill run and compared across supplement conditions.
Measured: During the fixed-pace 5 km treadmill run at each of the four experimental visits.
Respiratory Exchange Ratio
Respiratory exchange ratio (RER), calculated from oxygen consumption and carbon dioxide production, will be evaluated during the fixed-pace 5 km treadmill run and compared across supplement conditions.
Measured: During the fixed-pace 5 km treadmill run at each of the four experimental visits.
1-Minute Heart-Rate Recovery After the Fixed-Pace 5 km Treadmill Run
Heart-rate recovery will be calculated as the decrease in heart rate from the end of the fixed-pace 5 km treadmill run to 60 seconds after exercise cessation, expressed in beats per minute. Within-participant 1-minute heart-rate recovery will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Measured: From exercise cessation to 60 seconds after completion of the fixed-pace 5 km treadmill run at each of the four experimental visits.
Capillary Blood Lactate Concentration
Capillary blood lactate concentration will be measured using finger-prick blood sampling and a point-of-care analyzer before and after exercise. Pre- to post-exercise responses will be compared across supplement conditions.
Measured: Immediately before and immediately after the fixed-pace 5 km treadmill run at each experimental visit.
Capillary Blood Ketone Concentration
Capillary blood ketone concentration will be measured using finger-prick blood sampling and a point-of-care analyzer before and after exercise. Pre- to post-exercise responses will be compared across supplement conditions.
Measured: Immediately before and immediately after the fixed-pace 5 km treadmill run at each experimental visit.
Rating of Perceived Exertion
Rating of perceived exertion will be assessed using the Borg 6-20 Rating of Perceived Exertion scale, where 6 represents no exertion and 20 represents maximal exertion; higher scores indicate greater perceived exertion.
Measured: During and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Gastrointestinal Symptoms Severity
Gastrointestinal symptoms, including nausea, urge to vomit, bloating, belching, and abdominal cramping, will be assessed using visual analog scales anchored from no symptoms to the worst imaginable severity for each symptom. Higher values indicate greater symptom severity. Responses will be compared across the four supplement conditions.
Measured: During and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Subjective Fatigue
Participant-reported fatigue will be assessed using a single-item 0-10 numeric rating scale, where 0 indicates no fatigue and 10 indicates extreme fatigue. Scores and within-visit changes will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Measured: Immediately before supplement/placebo ingestion and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Subjective Energy Level
Participant-reported energy will be assessed using a single-item 0-10 numeric rating scale, where 0 indicates no energy at all and 10 indicates extremely high energy. Scores and within-visit changes will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Measured: Immediately before supplement/placebo ingestion and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Subjective Mental Focus
Participant-reported mental focus will be assessed using a single-item 0-10 numeric rating scale, where 0 indicates not at all focused and 10 indicates extremely focused. Scores and within-visit changes will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Measured: Immediately before supplement/placebo ingestion and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Participant-Reported Guess of Assigned Supplement Condition
Following each experimental visit, participants will report which supplement condition they believe they received. Responses will be summarized and compared with the actual assigned condition to evaluate participant perception of treatment assignment.
Measured: Immediately following completion of each experimental visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Exercise PhysiologyStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will be randomized in a 1:1:1:1 ratio to one of four treatment sequences using a four-period, four-treatment Williams square design (ABDC, BCAD, CDBA, DACB), where A = caffeine, B = L-citrulline, C = exogenous ketone, and D = placebo. This counterbalanced design balances treatment assignment across study periods and first-order carryover. Each participant will receive all four conditions and serve as their own control. Experimental visits will be separated by a minimum washout/recovery period of four days.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Louis University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hossein Rafiei, St. Louis University
- Investigators
- Hossein Rafiei, Principal investigator, St. Louis University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07854223
- Sponsor's protocol ID
- STUDY00000697
- Status last verified
- Sep 2026
- First submitted
- 26 Sep 2026
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared with outside researchers. Only de-identified, aggregate study results may be used for analysis, publication, or presentation, in accordance with the approved protocol and participant privacy protections.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fueling the Kilometers: Effects of Pre-Run Nutritional Supplements on Physiological Responses During a Fixed-Pace 5 km Treadmill Run
- ClinicalTrials.gov ID
- NCT07854223
- Acronym / sponsor ID
- STUDY00000697
- Conditions
- Exercise Physiology, Nutritional Supplementation
- Keywords
- Running Economy, Heart Rate Drift, Caffeine, L-Citrulline, Exogenous Ketones, Beta-Hydroxybutyrate, 5 km Running, Endurance Exercise
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- St. Louis UniversityUniversity, hospital or other
- Study start
- Oct 2026 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 2 Oct 2026 (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.
This study will examine how three commonly used pre-run nutritional supplements-caffeine, L-citrulline, and an exogenous ketone supplement-affect physiological and perceptual responses during a fixed-pace 5 km treadmill run in healthy, physically active runners.
Participants will complete one screening and baseline visit followed by four experimental visits in a randomized order. At each experimental visit, participants will receive caffeine, L-citrulline, an exogenous ketone supplement, or placebo before completing a fixed-pace 5 km treadmill run. Each participant will receive all four conditions and will therefore serve as their own control.
The study will evaluate measures including running economy, heart-rate responses, oxygen consumption, respiratory measures, blood lactate and ketone concentrations, perceived exertion, gastrointestinal symptoms, fatigue, energy, and focus. A randomly selected subgroup will also wear a continuous glucose monitor to explore glucose responses during the experimental visits. The study will also assess the feasibility and tolerability of completing repeated treadmill trials under the four supplement conditions.
Detailed description
This is a randomized, single-blind, placebo-controlled crossover study designed to compare acute physiological and perceptual responses to three pre-run nutritional supplements and placebo during a controlled fixed-pace 5 km treadmill run. Healthy, physically active runners will complete one screening/baseline visit and four experimental visits. Each participant will complete all four experimental conditions in randomized order and will serve as their own control. A minimum washout/recovery period of four days will separate experimental visits.
At each experimental visit, participants will receive one of four pre-run conditions: caffeine at 4 mg/kg body weight, L-citrulline at 7 g, an exogenous ketone supplement providing 11.5 g beta-hydroxybutyrate (BHB), or placebo. Study products will be provided in a standardized beverage vehicle, followed by a 45-minute waiting period before the treadmill run.
The primary physiological outcomes of interest are running economy and heart-rate drift during the fixed-pace 5 km treadmill run. Additional outcomes include oxygen consumption, carbon dioxide production, ventilation, respiratory exchange ratio, heart-rate recovery, capillary blood lactate and ketone concentrations, rating of perceived exertion, gastrointestinal symptoms, subjective fatigue, energy, focus, and participant-reported perceptions of the assigned supplement condition.
A prespecified randomly selected subgroup of up to 12 enrolled participants will use a Dexcom Stelo continuous glucose monitor during the experimental phase. CGM-derived glucose responses will be analyzed as exploratory outcomes within this subgroup only.
The study will also evaluate feasibility and tolerability, including visit completion, adverse events, supplement-related symptoms, gastrointestinal symptoms, and completeness of study measurements. The results are intended to characterize within-participant differences among the four conditions and provide preliminary data for future confirmatory studies.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- Participants will be randomized in a 1:1:1:1 ratio to one of four treatment sequences using a four-period, four-treatment Williams square design (ABDC, BCAD, CDBA, DACB), where A = caffeine, B = L-citrulline, C = exogenous ketone, and D = placebo. This counterbalanced design balances treatment assignment across study periods and first-order carryover. Each participant will receive all four conditions and serve as their own control. Experimental visits will be separated by a minimum washout/recovery period of four days.
| Arm | Type | Receives |
|---|---|---|
| Sequence 1: Caffeine-L-Citrulline-Placebo-Ketone | Experimental | Dietary Supplement: Caffeine, Dietary Supplement: L-Citrulline, Dietary Supplement: Exogenous Ketone (Beta-Hydroxybutyrate), Other: placebo beverageParticipants assigned to this randomized crossover sequence will receive caffeine, followed by L-citrulline, placebo, and exogenous ketone across four experimental visits. Each intervention will be administered 45 minutes before a fixed-pace 5 km treadmill run. Experimental visits will be separated by a minimum washout/recovery period of four days. |
| Sequence 2: L-Citrulline-Ketone-Caffeine-Placebo | Experimental | Dietary Supplement: Caffeine, Dietary Supplement: L-Citrulline, Dietary Supplement: Exogenous Ketone (Beta-Hydroxybutyrate), Other: placebo beverageParticipants assigned to this randomized crossover sequence will receive L-citrulline, followed by exogenous ketone, caffeine, and placebo across four experimental visits. Each intervention will be administered 45 minutes before a fixed-pace 5 km treadmill run. Experimental visits will be separated by a minimum washout/recovery period of four days. |
| Sequence 3: Ketone-Placebo-L-Citrulline-Caffeine | Experimental | Dietary Supplement: Caffeine, Dietary Supplement: L-Citrulline, Dietary Supplement: Exogenous Ketone (Beta-Hydroxybutyrate), Other: placebo beverageParticipants assigned to this randomized crossover sequence will receive exogenous ketone, followed by placebo, L-citrulline, and caffeine across four experimental visits. Each intervention will be administered 45 minutes before a fixed-pace 5 km treadmill run. Experimental visits will be separated by a minimum washout/recovery period of four days. |
| Sequence 4: Placebo-Caffeine-Ketone-L-Citrulline | Experimental | Dietary Supplement: Caffeine, Dietary Supplement: L-Citrulline, Dietary Supplement: Exogenous Ketone (Beta-Hydroxybutyrate), Other: placebo beverageParticipants assigned to this randomized crossover sequence will receive placebo, followed by caffeine, exogenous ketone, and L-citrulline across four experimental visits. Each intervention will be administered 45 minutes before a fixed-pace 5 km treadmill run. Experimental visits will be separated by a minimum washout/recovery period of four days. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age 18-35 years
- Healthy adult
- Able to provide written informed consent
- Regularly engaged in running-based aerobic training at least 3 times per week for at least 30 minutes per session during the past 3 months
- Able to complete a 5 km run in under 30 minutes
Key exclusion criteria (12 listed)
- Known cardiovascular, metabolic, pulmonary, or neurological disease that may increase the risk associated with exercise testing or materially influence study outcomes
- Uncontrolled hypertension or another cardiovascular condition that, in the investigator's judgment, makes vigorous treadmill exercise unsafe
- Diagnosed type 1 or type 2 diabetes mellitus or another known metabolic disease that may materially influence study outcomes
- Pregnant, breastfeeding, or planning pregnancy during the study period
- Current use of nitrate medications or phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil, tadalafil, or vardenafil
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 |
|---|---|---|
| CaffeineCaffeine will be administered at exactly 4 mg/kg body weight. The individualized dose will be calculated using body weight measured at the baseline visit. The commercially manufactured capsule contents will be weighed by trained study staff using a calibrated analytical balance to obtain the protocol-specified dose. Caffeine will be dispensed in the standardized study beverage and consumed 45 minutes before the fixed-pace 5 km treadmill run. | Dietary supplement | Sequence 1: Caffeine-L-Citrulline-Placebo-Ketone, Sequence 2: L-Citrulline-Ketone-Caffeine-Placebo, Sequence 3: Ketone-Placebo-L-Citrulline-Caffeine, Sequence 4: Placebo-Caffeine-Ketone-L-Citrulline |
| L-CitrullineL-citrulline will be administered at exactly 7.0 g. The commercially manufactured pure L-citrulline powder will be weighed using a calibrated analytical balance, dispensed in the standardized study beverage, and consumed 45 minutes before the fixed-pace 5 km treadmill run. | Dietary supplement | Sequence 1: Caffeine-L-Citrulline-Placebo-Ketone, Sequence 2: L-Citrulline-Ketone-Caffeine-Placebo, Sequence 3: Ketone-Placebo-L-Citrulline-Caffeine, Sequence 4: Placebo-Caffeine-Ketone-L-Citrulline |
| Exogenous Ketone (Beta-Hydroxybutyrate)The exogenous ketone condition will consist of one 15 g serving of Nutricost Ketone BHB Salt 4-in-1 Powder, providing 11.5 g beta-hydroxybutyrate (BHB) as calcium, magnesium, sodium, and potassium BHB salts. The supplement will be dispensed in the standardized study beverage and consumed 45 minutes before the fixed-pace 5 km treadmill run. | Dietary supplement | Sequence 1: Caffeine-L-Citrulline-Placebo-Ketone, Sequence 2: L-Citrulline-Ketone-Caffeine-Placebo, Sequence 3: Ketone-Placebo-L-Citrulline-Caffeine, Sequence 4: Placebo-Caffeine-Ketone-L-Citrulline |
| placebo beverageThe placebo will be a study-prepared beverage containing water, food-grade lime flavoring, and stevia, with no active study supplement. It will use the same standardized final volume as the active conditions and will be consumed 45 minutes before the fixed-pace 5 km treadmill run. | Other | Sequence 1: Caffeine-L-Citrulline-Placebo-Ketone, Sequence 2: L-Citrulline-Ketone-Caffeine-Placebo, Sequence 3: Ketone-Placebo-L-Citrulline-Caffeine, Sequence 4: Placebo-Caffeine-Ketone-L-Citrulline |
Primary outcome
Running Economy (VO₂) During the Fixed-Pace 5 km Treadmill Run
Time frame: During the fixed-pace 5 km treadmill run at each of the four experimental visits, approximately 45 minutes after supplement/placebo ingestion.
Running economy will be assessed using oxygen consumption (VO₂) measured by indirect calorimetry during standardized portions of the fixed-pace 5 km treadmill run. Within-participant running-economy responses will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
Heart-Rate Drift During the Fixed-Pace 5 km Treadmill Run
Time frame: Throughout the fixed-pace 5 km treadmill run at each of the four experimental visits, approximately 45 minutes after supplement/placebo ingestion.
Heart-rate drift will be assessed from continuous heart-rate monitoring as the change in heart rate over the course of the fixed-pace 5 km treadmill run. Within-participant heart-rate drift will be compared across the caffeine, L-citrulline, exogenous ketone, and placebo conditions.
13 secondary outcomes
Mean Oxygen Consumption (VO₂) During the Fixed-Pace 5 km Treadmill Run
Time frame: During the fixed-pace 5 km treadmill run at each of the four experimental visits, beginning approximately 45 minutes after supplement/placebo ingestion.
Mean Carbon Dioxide Production (VCO₂) During the Fixed-Pace 5 km Treadmill Run
Time frame: During the fixed-pace 5 km treadmill run at each of the four experimental visits, beginning approximately 45 minutes after supplement/placebo ingestion.
Ventilation
Time frame: During the fixed-pace 5 km treadmill run at each of the four experimental visits.
Respiratory Exchange Ratio
Time frame: During the fixed-pace 5 km treadmill run at each of the four experimental visits.
1-Minute Heart-Rate Recovery After the Fixed-Pace 5 km Treadmill Run
Time frame: From exercise cessation to 60 seconds after completion of the fixed-pace 5 km treadmill run at each of the four experimental visits.
Capillary Blood Lactate Concentration
Time frame: Immediately before and immediately after the fixed-pace 5 km treadmill run at each experimental visit.
Capillary Blood Ketone Concentration
Time frame: Immediately before and immediately after the fixed-pace 5 km treadmill run at each experimental visit.
Rating of Perceived Exertion
Time frame: During and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Gastrointestinal Symptoms Severity
Time frame: During and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Subjective Fatigue
Time frame: Immediately before supplement/placebo ingestion and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Subjective Energy Level
Time frame: Immediately before supplement/placebo ingestion and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Subjective Mental Focus
Time frame: Immediately before supplement/placebo ingestion and immediately following the fixed-pace 5 km treadmill run at each experimental visit.
Participant-Reported Guess of Assigned Supplement Condition
Time frame: Immediately following completion of each experimental visit.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared with outside researchers. Only de-identified, aggregate study results may be used for analysis, publication, or presentation, in accordance with the approved protocol and participant privacy protections.
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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.
Hossein Rafiei principal investigator
St. Louis University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Caffeine, L-Citrulline and Exogenous Ketone (Beta-Hydroxybutyrate) in people with Exercise Physiology and Nutritional Supplementation, run by St. Louis University 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 7 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 2 Oct 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hossein Rafiei, PhD, RD, ACSM-CPT (314-977-8675, hossein.rafiei@health.slu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Running Economy (VO₂) During the Fixed-Pace 5 km Treadmill Run (time frame: During the fixed-pace 5 km treadmill run at each of the four experimental visits, approximately 45 minutes after supplement/placebo ingestion.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Oct 2026.