Neurophysiological Mechanisms of Placebo and Nocebo Effects in Sports - a Protocol Paper

Not Applicable

Not yet recruiting

• Conditions: Placebo Effect; Nocebo Effect

• Registration Number: NCT06835777
• Lead Sponsor: Canterbury Christ Church University

Brief Summary

This clinical trial aims to investigate the neurophysiological mechanisms of placebo and nocebo effects on sports performance, using Electroencephalography (EEG) and isometric strength testing of the lower extremities.

The primary objective of this trial is to identify temporal mechanisms and cortical regions and networks involved in generating placebo and nocebo effects before (expectation) and at onset of athletic performance (perception).

The trial will include four groups, two of them experimental, one an active control and one natural history, meaning participants in this group will receive no intervention and won't be EEG controlled. Data will be collected on two occasions with baseline data for EEG, expectations and performance as well as key participant characteristics being collected on day one. On day two, in a deceptive process, participants in the two experimental groups will take an inert substance presented as either performance enhancing or inhibiting and subsequently experience a reinforcement of beliefs via exposure to explicit adjectives. EEG data will be collected during reinforcement of beliefs. In the active control group, participants will receive no substance, but this group will follow the same procedure as the experimental groups with neutral adjectives. Participants will then perform isometric strength and fatigue resistance tests on an isometric dynamometer. EEG data as well as subjective data on expectations and rating of perceived exhaustion will be collected.

Detailed Description

This trial will examine temporal and spatial aspects of neurophysiological mechanisms behind nocebo and placebo effects before (expectation) and at exercise onset (perception) using high-density EEG. It will further investigate possible predictors of responsiveness and non-responsiveness to acute placebo and nocebo stimuli in the context of sports, notably interpretating psychological mechanisms (e.g. personality, beliefs, expectations) as well as temporal neurophysiological measures.

This study is designed as a randomized, controlled clinical trial (RCT) with data collection on two different occasions and four parallel groups: 1) positive-expectations, 2) negative-expectations, 3) control, and 4) natural history.

The first three groups will be addressed as intervention groups. On the first visit, participants' baseline data, specifically performance measures (all groups) and EEG data (all but natural history), as well as key characteristics will be collected. On the second visit, in the belief groups, participants will receive an in-person manipulation of beliefs and two placebo pills and will be informed that they are expected to positively (positive-expectations) or negatively (negative-expectations) affect their isometric strength and fatigue resistance measured using a Biodex System 4 Isokinetic Dynamometer in a 5x5sec test protocol with a minimum of 1 minute rest in between sets. In addition, after a resting period of three minutes, they will perform an isometric knee extension hold to failure at 60% MVC. The control group and the natural history group will receive no pills, with the control group receiving a neutral explanation of EEG data, its relevance and general information about isometric strength testing and the natural history group not receiving EEG at all, but serving as a control to the potential influence of experiencing an EEG set up on performance measures. The primary endpoints of this trial are placebo and nocebo induced changes in EEG signaling via Event Related Potentials (ERPs) during administration of reinforcements of beliefs through words as well as during expectancy and perception phases of physical performance.

The key question of this trial is whether participants exposed to placebo or nocebo stimuli will exhibit distinct neural activity pattern (temporal and spatial) in the context of sports performance. The second major question is, whether individual differences in character traits and states as well as motivation and beliefs can significantly predict the magnitude or likeliness of placebo and nocebo responses in participants' performance in an isometric strength and fatigue resistance task. In addition, EEG data to better understand the valence of and emotional response to words will be used to further investigate how semantics and our choice of words influence susceptibility to placebo and nocebo effects in other people. Several elements that were not adequately addressed in previous studies will be incorporated into this RCT:

(1) temporal and spatial aspects of neural correlates of placebo and nocebo effects in sports, (2) hard data (EEG) on how an individual reacts to semantic implications on performance and (3) correlation of subjective ratings of expectations of performance and data from neural processes associated with affective processing, emotional valence and motivation (LPP,LPC) and anticipation as well as motor preparation (CNV). To further understand the above point may result in a change on how athletes, coaches and therapists approach placebo and nocebo effects in the context of sports performance.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-10
• Study First Submitted QC: 2025-02-13
• Last Update Submitted: 2025-02-13
• Study First Posted: 2025-02-19
• Last Update Posted: 2025-02-19
• Study Start: 2025-03-01
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• Healthy adult participants (18+)
• physically active (WHO, 2020)
• no medical history pf psychological disorders/mental health issues
• no acute or regular medication intake
• no severe injury to the lower limb within the last 6 months
• proficient in english
• normal or corrected eyesight

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
EEG data - performance	From collection of baseline data on day one to the end of day two of data collection.	Temporal neurophysiological data measured by EEG. The Continuous Negative Variation (CNV), an Event Related Potential (ERP), will be used to differentiate positive and negative expectations as well as motor preparation before and at onset of isometric strength testing.
EEG data - reinforcement of beliefs	From collection of baseline data on day one to the end of day two of data collection.	Event related potentials (ERP) will be investigated during the reinforcement of beliefs, specifically the late positive potential (LPP) and the late positive component (LPC).
EEG, exploratory source analysis	From collection of baseline data on day one to the end of day two of data collection	In addition to ERP data, Low-Resolution Electromagnetic Tomography (LORETA) will be used in an exploratory approach to identify specific neural origins associated with placebo and nocebo responses.

Secondary Outcome Measures

Name	Time	Method
Performance Output, Isometric Forces	From collection of baseline data on day one to the end of day two of data collection.	Peak Isometric Force: Measured in Newton-meters (Nm) as the maximum force output during a 5-second unilateral knee extension contraction.; Average Isometric Force: Calculated as the mean force output in Nm maintained over a 5-second unilateral knee extension contraction.; Isometric Force output data will be analysed in a within and between analysis, the latter being normalized to body mass (Nm/kg).
Performance Output, Force Consistency	From collection of baseline data on day one to the end of day two of data collection.	Force Consistency: Assessed by comparing peak and average force outputs in Nm across five consecutive trials of 5-second contractions.
Performance Output, Endurance Hold and Fatigue Resistance	From collection of baseline data on day one to the end of day two of data collection.	Fatigue Resistance and Endurance Hold: Evaluating the time to failure at the 60% maximally voluntary contraction (MVC) hold.
Performance Output, Recovery Capacity	From collection of baseline data on day one to the end of day two of data collection.	Recovery Capacity: Determined by examining the ability to maintain force output in Nm across trials with 1-minute rest intervals between contractions.
Heartrate	From collection of baseline data on day one to the end of day two of data collection.	Heartrate (bpm) will be collected during and before physical performance as well as during EEG data collection.
Rate of Perceived Exertion (RPE)	From collection of baseline data on day one to the end of day two of data collection.	Rate of perceived exertion (RPE) will be used to assess subjective effort and closeness to failure after isometric strength testing
Electromyographic (EMG) Data	From collection of baseline data on day one to the end of day two of data collection.	EMG data of the M. vastus lateralis of the dominant leg during isometric performance tests will be collected.

Trial Locations

Locations (1)

Canterbury Christ Church University; 🇬🇧 Canterbury, Kent, United Kingdom