Placebo Effect on Cycling Performance: Laboratory Crossover Study

The Impact of Expectations on Physical Performance and Psychophysiological Potential: a Randomized, Double-blind, Placebo-controlled Crossover Study on the Placebo Effect in the Context of Caffeine Supplementation

This study aims to determine the impact of the placebo (PLA) effect on physical and cognitive performance in a controlled laboratory setting. The study investigates how expectations and beliefs about substance intake (caffeine vs. placebo) interact with actual consumption to influence performance and physiological stress markers. Healthy adults (n = 80) will participate in four testing sessions using a randomized, double-blind, placebo-controlled crossover design. Physiological stress markers (cortisol and alpha-amylase), heart rate, and performance metrics will be monitored during a standardized cycling exercise protocol. This phase provides the dense mechanistic data required to refine a mathematical model of the placebo effect, offering insights into how individual personality traits and cognitive anchoring influence psychophysiological potential.

Study Overview

• Status: Not yet recruiting
• Conditions: Cognitive Performance; Placebo Effect; Physical Performance
• Intervention / Treatment: Drug: Caffeine (6mg/kg); Other: Placebo (Starch capsule)

Detailed Description

This study employs a randomized, double-blind, placebo-controlled crossover design to conduct a multifactorial analysis of psychophysiological and biomechanical dynamics. Participants (n = 80, aged 20-35 years) will complete four experimental sessions separated by 7-day washout periods, involving caffeine (6 mg/kg) or placebo administration. The laboratory protocol (160 minutes) integrates multiple modalities: (1) cognitive testing (Reaction Time Test and Flanker Test), (2) postural control assessment using the BTrackS Balance Plate, and (3) a standardized cycle ergometer exercise protocol consisting of 15 minutes at the anaerobic threshold followed by a 5-minute self-paced maximal effort trial. Belief manipulation (immediate vs. retrospective reporting) and cognitive anchoring (feedback conditions) are implemented to isolate expectancy-driven effects. Continuous metabolic and cardiorespiratory data collected using the Cosmed K5 system will be synchronized with blood biomarkers (lactate, glucose, caffeine, and paraxanthine) and salivary biomarkers (cortisol, testosterone, and alpha-amylase). Advanced statistical methods, including Functional Data Analysis (FDA) and machine learning, will be used to integrate physiological trajectories with behavioral predictors.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jakub Malik, PhD; Phone Number: +48739975701; Email: malik@awf.poznan.pl

Study Locations

• Poland
  • Wielkopolska
    • Poznan, Wielkopolska, Poland
      • Poznan University of Physical Education
      • Contact: Jakub Malik, PhD; Phone Number: +48739975701; Email: malik@awf.poznan.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age between 20 and 30 years,
• Healthy adults,
• Regular physical activity, but not professional athletes,
• Normal or corrected-to-normal vision,
• Habitual caffeine consumption.

Exclusion Criteria:

• History of neurological, psychiatric, cardiovascular, or metabolic disorders,
• Current use of medication or supplements affecting the central nervous system,
• Musculoskeletal injuries that would impair physical performance,
• No habitual caffeine consumption or severe negative side effects of caffeine,
• Diagnosed sleep disorders or chronic fatigue,
• Diagnosed major depressive disorder or other severe psychiatric conditions,
• Presence of any menstrual disorders,
• Inability to attend all experimental study visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AABB; Participants follow the sequence: Caffeine, Caffeine, Placebo, Placebo, with a 7-day washout period between sessions.	Drug: Caffeine (6mg/kg); Anhydrous caffeine administered in an encapsulated form at a dosage of 6 mg per kilogram of body mass, 60 minutes before the exercise protocol.; Other: Placebo (Starch capsule); Corn starch administered in an identical encapsulated form as the active caffeine, 60 minutes prior to the laboratory exercise protocol.
Experimental: Sequence BBAA; Participants follow the sequence: Placebo, Placebo, Caffeine, Caffeine, with a 7-day washout period between sessions.	Drug: Caffeine (6mg/kg); Anhydrous caffeine administered in an encapsulated form at a dosage of 6 mg per kilogram of body mass, 60 minutes before the exercise protocol.; Other: Placebo (Starch capsule); Corn starch administered in an identical encapsulated form as the active caffeine, 60 minutes prior to the laboratory exercise protocol.
Experimental: Sequence ABAB; Participants follow the sequence: Caffeine, Placebo, Caffeine, Placebo, with a 7-day washout period between sessions.	Drug: Caffeine (6mg/kg); Anhydrous caffeine administered in an encapsulated form at a dosage of 6 mg per kilogram of body mass, 60 minutes before the exercise protocol.; Other: Placebo (Starch capsule); Corn starch administered in an identical encapsulated form as the active caffeine, 60 minutes prior to the laboratory exercise protocol.
Experimental: Sequence BABA; Participants follow the sequence: Placebo, Caffeine, Placebo, Caffeine, with a 7-day washout period between sessions.	Drug: Caffeine (6mg/kg); Anhydrous caffeine administered in an encapsulated form at a dosage of 6 mg per kilogram of body mass, 60 minutes before the exercise protocol.; Other: Placebo (Starch capsule); Corn starch administered in an identical encapsulated form as the active caffeine, 60 minutes prior to the laboratory exercise protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Work Capacity (total work in J)	Total physical work performed, expressed in Joules (J), during the standardized laboratory exercise protocol, including both the Anaerobic Threshold phase and the Self-paced Maximal Time-trial.	Measured during each laboratory exercise protocol (approximately 85-120 minutes).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise Heart Rate (bpm)	Heart rate expressed in beats per minute (bpm) recorded continuously throughout the standardized laboratory exercise protocol.	Measured continuously during each laboratory exercise protocol (approximately 85-120 minutes).
Exercise Heart Rate Variability (ms)	Heart rate variability expressed in milliseconds (ms) and recorded continuously throughout the standardized laboratory exercise protocol to assess autonomic regulation.	Measured continuously during each laboratory exercise protocol (approximately 85-120 minutes).
Salivary Cortisol Concentration (nmol/L)	Salivary cortisol concentration expressed in nmol/L.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, after warm-up (60 minutes post-ingestion), and 3 minutes post-exercise.
Salivary Testosterone Concentration (pmol/L)	Salivary testosterone concentration expressed in pmol/L.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, after warm-up (60 minutes post-ingestion), and 3 minutes post-exercise.
Salivary Alpha-amylase Activity (U/L)	Salivary alpha-amylase activity expressed in U/L.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, after warm-up (60 minutes post-ingestion), and 3 minutes post-exercise.
Simple Reaction Time (ms)	Reaction time during the Simple Reaction Time test expressed in milliseconds (ms).	Measured at T1 (pre-ingestion, minute 2 of the protocol), T2 (post-ingestion/pre-exercise, minute 55 of the protocol), and T3 (post-exercise, minute 125 of the protocol).
Heart Rate Recovery (bpm)	Heart rate recorded during the post-exercise recovery period, expressed in beats per minute (bpm).	Measured continuously during the first 5 minutes immediately following exercise cessation.
Postural Control (mm)	Center of Pressure excursions measured using the BTrackS Balance Plate and expressed in millimeters (mm).	Measured continuously during the exercise protocol and at T1 (minute 2), T2 (minute 55), and T3 (minute 125).
Rating of Perceived Exertion (Borg Scale, points)	Perceived exertion will be assessed using the Borg Rating of Perceived Exertion Scale and reported in points (6-20).	Before and immediately after warm-up, immediately after the Anaerobic Threshold phase, immediately after the Self-paced Maximal Time-trial, and immediately after cooldown during each laboratory study visit.
Personality Traits (NEO-FFI, points)	Personality traits will be assessed using the NEO Five-Factor Inventory (NEO-FFI). The questionnaire provides scores for five personality domains: Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Results will be reported as domain scores in points.	Measured at baseline (first study visit).
Mood State (POMS/BRUMS) (points)	Mood state assessed using the Profile of Mood States (POMS/BRUMS), expressed in points.	Measured during each laboratory study visit.
Caffeine Expectancy (Caff-EQ-Brief) (points)	Caffeine expectancy assessed using the Caffeine Expectancy Questionnaire-Brief (Caff-EQ-Brief), expressed in points.	Measured 30 minutes post-ingestion.
Urine pH	Urine pH measured using a urine strip analyzer.	Measured once prior to the start of each laboratory study visit.
White blood cells count and differential (count/L)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
White blood cells count and differential (%)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (red blood cells, RBC) (count/L)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (hemoglobin concentration, HGB) (mmol/L)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (hematocrit, HCT) (L/L)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (mean corpuscular volume, MCV; mean platelet volume, MPV) (fL)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (mean corpuscular hemoglobin mass, MCH) (fmol)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (mean corpuscular hemoglobin concentration, MCHC) (mmol/L)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (platelet count, PLT) (count/L)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (platelet hematocrit, PCT) (cL/L)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (platelet distribution width, PDW; platelet large cell ratio, PLCR; red blood cells distribution width - coefficient of variation, RDW-C) (%)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Hematological indices (red blood cells distribution width - standard deviation, RDW-S) (fL)	Assessment of the hematological parameter will be performed from fingertip capillary blood collected before supplementation (baseline), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Urea Concentration (mmol/L)	Urea concentration measured from fingertip capillary blood and expressed in mmol/L.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Glucose Concentration (mg/dL)	Glucose concentration measured from fingertip capillary blood and expressed in mg/dL.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Creatinine concentration (μmol/L)	Creatinine concentration measured from fingertip capillary blood and expressed in µmol/L.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Muscle damage markers (activity of alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase) (U/L)	Assessment of the muscle damage markers (activity of alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase) (U/L) will be performed from fingertip capillary blood.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Lactate concentration (mmol/L)	Blood lactate concentration measured from fingertip capillary blood and expressed in mmol/L.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Electrolites' concentration (Ca, Na, K, Cl) (mmol/L)	Assessment of electrolites' concentration (Ca, Na, K, Cl) (mmol/L) will be performed from fingertip capillary blood.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Blood pH	Assessment of gasometry markers (blood pH) will be performed from fingertip capillary blood.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Partial Pressure of Carbon Dioxide and Oxygen (pCO2, pO2) (mmHg)	Assessment of gasometry markers (pCO2, pO2) (mmHg) will be performed from fingertip capillary blood.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
CAF and PAX concentrations (µmol/L)	Assessment of caffeine and paraxanthine concentrations (µmol/L) will be performed from fingertip capillary blood.	Measured at baseline (pre-supplementation), 30 minutes post-ingestion, before exercise, and 3 minutes post-exercise.
Static weight distribution (mm)	Static weight distribution expressed in millimeters of Center of Pressure symmetry.	Measured at the start of each study visit.
Analysis of body composition (fat-free mass, fat mass) (kg)	Assessment of body composition (fat-free mass, fat mass) (kg) will be carried out at the start of each study visit.	Measured at the start of each study visit.
Analysis of body composition (total body water) (L)	Assessment of body composition (total body water) (L) will be carried out at the start of each study visit.	Measured at the start of each study visit.
Analysis of body composition (total body water) (%)	Assessment of body composition (total body water) (%) will be carried out at the start of each study visit.	Measured at the start of each study visit.
Autonomic Response during Cognitive Performance (bpm)	Heart rate and heart rate variability recording during cognitive testing blocks, expressed in beats per minute (bpm).	Measured at three time points: T1 (pre-ingestion; 2 minute of protocol), T2 (post-ingestion/pre-exercise; 55 minute of protocol), and T3 (post-exercise; 125 minute of protocol).
Anthropometric Indices (kg)	Body mass in kilograms will be measured at the start of each study visit.	Measured at the start of each study visit.
Anthropometric Indices (metres)	Height in metres will be measured at the start of each study visit.	Measured at the start of each study visit.
Explosive power variables (ms)	Explosive lower-limb power variables expressed in milliseconds (ms) - Countermovement Jump - contact time and flight time.	Continuous recording throughout the exercise protocol and discrete assessments at T1 (2 minute of protocol), T2 (55 minute of protocol), and T3 (125 minute of protocol).
Explosive power variables (W)	Explosive lower-limb power expressed in Watts (W) - Countermovement Jump - power.	Continuous recording throughout the exercise protocol and discrete assessments at T1 (2 minute of protocol), T2 (55 minute of protocol), and T3 (125 minute of protocol).
Explosive power variables (mm)	Explosive lower-limb power expressed in millimeters (mm) - Countermovement Jump - height.	Continuous recording throughout the exercise protocol and discrete assessments at T1 (2 minute of protocol), T2 (55 minute of protocol), and T3 (125 minute of protocol).
Hydration Status (g/mL)	Assessment of urine specific gravity (g/mL) using a urine strip analyzer.	Once prior to the start of each laboratory study visit.
Psychomotor Vigilance Test Reaction Time (ms)	Reaction time during the Psychomotor Vigilance Test expressed in milliseconds (ms).	Measured at T1 (pre-ingestion, minute 2 of the protocol), T2 (post-ingestion/pre-exercise, minute 55 of the protocol), and T3 (post-exercise, minute 125 of the protocol).
Flanker Test Reaction Time (ms)	Reaction time during the Flanker Test expressed in milliseconds (ms).	Measured at T1 (pre-ingestion, minute 2 of the protocol), T2 (post-ingestion/pre-exercise, minute 55 of the protocol), and T3 (post-exercise, minute 125 of the protocol).
Flanker Test Accuracy (%)	Accuracy during the Flanker Test expressed as the percentage of correct responses.	Measured at T1 (pre-ingestion, minute 2 of the protocol), T2 (post-ingestion/pre-exercise, minute 55 of the protocol), and T3 (post-exercise, minute 125 of the protocol).
Heart Rate Variability Recovery (ms)	Heart rate variability expressed in milliseconds (ms) during the post-exercise recovery period.	Measured continuously during the first 5 minutes immediately following exercise cessation.
Caffeine Expectancy Questionnaire Score (points)	Caffeine expectancy assessed using the Caffeine Expectancy Questionnaire and expressed in points.	Measured 30 minutes post-ingestion.
Suggestibility (SSS) (points)	General suggestibility assessed using the Short Suggestibility Scale (SSS), expressed in points.	Measured during the last study visit.
Intrinsic Motivation (IMI) (points)	Task-specific intrinsic motivation assessed using the Intrinsic Motivation Inventory (IMI), expressed in points.	Measured after each test block during every laboratory study visit.
Sport Motivation (SMS) (points)	Sport motivation assessed using the Sport Motivation Scale (SMS), expressed in points.	Measured during the first study visit.
Sleep Quality (LSEQ) (points)	Subjective sleep quality assessed using the Leeds Sleep Evaluation Questionnaire (LSEQ), expressed in points.	Measured once during each laboratory study visit.

Collaborators and Investigators

• Sponsor: Poznan University of Physical Education
• Investigators: Principal Investigator: Jakub Malik, PhD, Poznan University of Physical Education, Department of Sports Psychology

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: July 21, 2026
• First Submitted That Met QC Criteria: July 31, 2026
• First Posted (Actual): August 5, 2026

Study Record Updates

• Last Update Posted (Actual): August 5, 2026
• Last Update Submitted That Met QC Criteria: July 31, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Caffeine; Psychophysiology; Expectancy; Postural Control; Human Performance; Exercise PHysiology
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dietary Carbohydrates; Carbohydrates; Alkaloids; Purinones; Purines; Polymers; Macromolecular Substances; Polysaccharides; Glucans; Biopolymers; Xanthines; Caffeine; Starch
• Other Study ID Numbers: 152-2-26; 2025/57/N/NZ4/04470 (Other Grant/Funding Number: National Science Centre)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol will be published as an open-access article. Upon completion of the study, de-identified individual participant data (IPD) and relevant analytic code will be deposited in an open-access repository such as Zenodo or OSF, following the FAIR principles.
• IPD Sharing Time Frame: The study protocol will be available upon its publication. The IPD and analytic code will be available starting from the date of the primary study results publication and will remain accessible for at least 5 years.
• IPD Sharing Access Criteria: The study protocol will be published as an open-access article. Upon completion of the study, de-identified individual participant data (IPD) and relevant analytic code will be deposited in an open-access repository such as Zenodo or OSF, in accordance with FAIR principles.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No