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Completed

NCT Number: NCT07410195

Resistance Training Adaptations and Caffeine Intake

This parallel-group, randomized, double-blind, placebo-controlled trial investigates the effects of three different caffeine supplementation strategies on resistance training-induced adaptations in 120 caffeine-naive, inactive young adult males. Participants will undergo a 10-week supervised resistance training program. The four supplementation strategies are: (1) constant daily low-moderate dosing (4 mg/kg/day), (2) gradually escalating dose (2 to 6 mg/kg across weeks), (3) training-day-only caffeine (4 mg/kg/day), and (4) placebo. Primary outcomes include maximal strength, body composition (lean body mass and fat mass), skeletal muscle thickness, and training volume progression. Secondary outcomes include muscular endurance, jump height, flight-time-to-contraction-time (FT:CT) ratio, mechanistic/biological variables (epinephrine, norepinephrine, cortisol, testosterone, creatine kinase, IGF-1), rate of perceived exertion, sleep/recovery parameters, and adverse effects.

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Key information

Conditions

Muscle Hypotrophy Adaptation Atrophy Exercise Performance Hypertrophy Muscle Strength Muscular Atrophy Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–30 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Istanbul University-Cerrahpasa, Faculty of Sport Sciences Performance Laboratory

Istanbul, Avcilar, 34010, Turkey (Türkiye)

About this study

BACKGROUND: Caffeine is a well-established acute ergogenic aid that reliably improves endurance, power, and resistance-exercise performance when consumed at typical ergogenic doses (approximately 2-6 mg/kg about 60 minutes pre-exercise). However, whether caffeine exerts direct biological effects on muscle protein balance and hypertrophy remains unclear. Regular caffeine ingestion produces partial physiological tolerance, creating the possibility that chronic supplementation elicits different outcomes than acute dosing. OBJECTIVES: This study addresses three translational questions: (1) Does constant daily low-moderate dosing potentiate training adaptations? (2) Does a gradually escalating dose strategy produce greater effects by overcoming tolerance? (3) Does training-day-only caffeine preserve acute ergogenic effects while limiting tolerance and sleep disturbance? METHODS: 120 caffeine-naive, physically inactive young adult males aged 18-30 years will be randomly assigned to one of the following groups (n=30 per group): (1) constant daily low-moderate dosing (CON, 4 mg/kg/day), (2) gradually escalating dose (ESC, 2 to 6 mg/kg across weeks), (3) training-day-only caffeine (TDO, 4 mg/kg/day), and (4) placebo (PLA). All participants will undergo supervised resistance training 3 times per week. OUTCOMES: Primary endpoints include maximal strength, body composition (lean body mass and fat mass), skeletal muscle thickness, and training volume metrics. Secondary outcomes include muscular endurance, jump height, flight-time-to-contraction-time (FT:CT) ratio, mechanistic/biological variables (epinephrine, norepinephrine, cortisol, testosterone, creatine kinase, IGF-1), rate of perceived exertion, sleep/recovery parameters, and adverse effects. STATISTICAL ANALYSIS: Linear Mixed Models will be used to analyze the data.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male sex and age between 18 and 30 years
  • Daily caffeine intake <100 mg/day
  • resistance-training experience ≥1 year and <3 years
  • Body mass index (BMI) between 18.5-25 kg/m2
  • Willingness to attend all training and testing sessions regularly
  • Provision of written informed consent after being fully informed about the study

Exclusion criteria

  • Presence of cardiovascular, metabolic, renal, hepatic, or other serious chronic diseases
  • Diagnosed psychiatric disorders or severe caffeine intolerance/allergy
  • Use of medications affecting caffeine metabolism or muscle anabolism (e.g., beta-blockers, antidepressants, anabolic steroids)
  • Musculoskeletal injuries that prevent safe resistance training
  • Smoking or alcohol consumption at levels that could affect study outcomes
  • Concurrent participation in another exercise intervention study
  • Inability to tolerate DXA scanning or blood sampling

Treatment and study plan

Caffeine (Constant Daily Dose)

Dietary Supplement

Oral caffeine capsule at 4 mg/kg body weight, consumed daily approximately 60 minutes before training sessions (on training days) or at the same time of day (on rest days).

Caffeine (Escalating Dose)

Dietary Supplement
  • Oral caffeine starting at 2 mg/kg/day and increasing incrementally to reach 6 mg/kg/day by week 10.

Caffeine (Training Days Only)

Dietary Supplement

Oral caffeine capsule at 4 mg/kg body weight, consumed only on training days approximately 60 minutes before exercise.

placebo capsule

Dietary Supplement

Oral placebo capsule (250 mg cellulose), consumed daily approximately 60 minutes before training sessions (on training days) or at the same time of day (on rest days).

Primary outcomes

  1. Change in Lean Body Mass Measured by DXA

    Time frame: Baseline and post-test (after completing 10 weeks of interventions)

    Change in total lean body mass measured using dual-energy X-ray absorptiometry (DXA), reported in kilograms.

  2. Change in Fat Mass Measured by DXA

    Time frame: Baseline and post-test (after completing 10 weeks of interventions)

    Change in fat mass measured using DXA.

  3. Maximal Strength

    Time frame: Baseline, and post-test (after completing 10 weeks of interventions)

    Measure by one-repetition maximum (1-RM) on a lower body (Smith machine Back Squat) and two upper body (Bench Press machine and Lat Pulldown machine) exercises.

  4. Total Training Volume Load

    Time frame: During the intervention period (all training sessions).

    Total training volume load calculated as the sum of lifted load using the formula (kilograms × repetitions × sets) accumulated during each intervention period.

  5. Change in Skeletal Muscle Thickness

    Time frame: Baseline and post-test (after completing 10 weeks of interventions)

    Change in skeletal muscle thickness measured using B-mode ultrasound, reported in mm.

Secondary outcomes

  1. Muscular endurance

    Time frame: Baseline, and post-test (after completing 10 weeks of interventions)

    It will be measured by a repetitions-to-failure test on the Smith machine back squat using a load corresponding to 60% of the current 1RM.

  2. Neuromuscular function

    Time frame: Baseline and post-test (after completing 10 weeks of interventions)

    It will be measured by the countermovement jump (CMJ) test on a force platform.

  3. Resting concentrations of testosterone

    Time frame: Baseline, and post-test (after completing 10 weeks of interventions)

    They will be measured using standard biochemical analyses.

  4. Plasma epinephrine responses to exercise

    Time frame: During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.

    They will be measured using standard biochemical analyses.

  5. Recovery

    Time frame: Before each of the 30 training sessions during the study.

    It will be assessed using the validated 0-10 Perceived Recovery Status Scale (0 to 2: very poorly recovered, 3 to 4: poorly recovered, 5 to 6: adequately recovered, 7 to 8: well recovered, and 9 to 10: fully recovered).

  6. Adverse Events

    Time frame: From initiation of the 4-week caffeine abstinence period through completion of the post-intervention assessments, monitored throughout the study (approximately 16 weeks).

    Adverse events will be assessed using a standardized questionnaire administered throughout the study.

  7. Sleep quality

    Time frame: Baseline and post-test (after completing 10 weeks of interventions).

    It will be assessed by the Pittsburgh Sleep Quality Index (PSQI).

  8. Rate of perceived exertion

    Time frame: After each supervised training session, participants were assessed throughout the 10-week intervention period (30 training sessions).

    Assessed using the Borg Category-Ratio (CR10) Scale, ranging from 0 ("nothing at all") to 10 ("maximal"). Participants will report their perceived exertion after each supervised training session.

  9. Resting concentrations of insulin-like growth factor-1 (IGF-1)

    Time frame: Baseline, and post-test (after completing 10 weeks of interventions)

    They will be measured using standard biochemical analyses.

  10. Resting concentrations of cortisol

    Time frame: Baseline, and post-test (after completing 10 weeks of interventions)

    They will be measured using standard biochemical analyses.

  11. Resting concentrations of creatine kinase

    Time frame: Baseline, and post-test (after completing 10 weeks of interventions)

    They will be measured using standard biochemical analyses.

  12. Serum cortisol responses to exercise

    Time frame: During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.

    They will be measured using standard biochemical analyses.

  13. Plasma norepinephrine responses to exercise

    Time frame: During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.

    They will be measured using standard biochemical analyses.

Sponsors and collaborators

Lead sponsor

Istanbul University - Cerrahpasa

Other

Collaborators

  • İstanbul Yeni Yüzyıl Üniversitesi

Registry information

Official study title

Study of Different Caffeine Supplementation Strategies on Resistance Training-Induced Adaptations

Important dates

Study start
2026
Primary completion
2026
Study completion
2026
First posted
Feb 13, 2026
Registry last updated
Jul 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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