Recruiting

Caffeine, L-Citrulline, Ketone

Sponsor:

St. Louis University

Code:

NCT07854223

Conditions

Exercise Physiology

Nutritional Supplementation

Eligibility Criteria

Sex: All

Age: 18 - 35

Healthy Volunteers: Accepted

Interventions

Caffeine

L-Citrulline

Exogenous Ketone (Beta-Hydroxybutyrate)

placebo beverage

Study Details

Brief 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.

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.

Conditions

Exercise Physiology

Nutritional Supplementation

Study ID

NCT07854223

Start date

Oct, 2026

Status verified date

Sep, 2026

Completion date

Aug, 2027

Anticipated

Primary completion date

Mar, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 35

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Sequence 1: Caffeine-L-Citrulline-Placebo-Ketone

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.

experimental: Sequence 2: L-Citrulline-Ketone-Caffeine-Placebo

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.

experimental: Sequence 3: Ketone-Placebo-L-Citrulline-Caffeine

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.

experimental: Sequence 4: Placebo-Caffeine-Ketone-L-Citrulline

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.

Interventions

Caffeine

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-Citrulline

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)

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 beverage

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.

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. ]
  • 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. ]

Central Contacts and Locations

Central contacts

Hossein Rafiei, PhD, RD, ACSM-CPT

314-977-8675hossein.rafiei@health.slu.edu

Locations

Saint Louis University, Allied Health Building

Recruiting

St Louis, Missouri, United States, 63104

Contacts

Hossein Rafiei, PhD RD

314-977-8675hossein.rafiei@health.slu.edu

hossein.rafiei@health.slu.edu

Principal Investigator:

Hossein Rafiei, PhD, RD, ACSM-CPT

More Information

Sponsor

St. Louis University

Last update posted

Oct 2, 2026

Last verified

Sep, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-03. This information was provided to ClinicalTrials.gov by St. Louis University on 2026-10-02. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.