Clinical trial NCT06835777: Neurophysiological Mechanisms of Placebo and Nocebo Effects in Sports - a Protocol Paper
Official title: Neurophysiological Mechanisms of Placebo and Nocebo Effects in Sports - Protocol Paper of a Randomised Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Placebo Effect
Nocebo Effect
Keywords: EEG
Placebo
Nocebo
Sports Performance
Lead sponsor: Canterbury Christ Church University
Sponsor class: OTHER
First posted: 2025-02-19
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomised controlled trail, four parallel arms (positive-expectations, negative-expectations, control , natural history)
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: EEG data - performance
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: EEG data - reinforcement of beliefs
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: EEG, exploratory source analysis
timeFrame: From collection of baseline data on day one to the end of day two of data collection
Secondary outcomes:
measure: Performance Output, Isometric Forces
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Performance Output, Force Consistency
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Performance Output, Endurance Hold and Fatigue Resistance
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Performance Output, Recovery Capacity
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Heartrate
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Rate of Perceived Exertion (RPE)
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Electromyographic (EMG) Data
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
Other outcomes:
measure: Questionnaires - Anxiety
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Questionnaires - Motivation and Perception of Ability
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Questionnaires - Optimism
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Questionnaires - Sport supplement use and belief
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Questionnaires - Resilience
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Questionnaires - Sensitivity
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Questionnaires - Emotions
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
measure: Questionnaires - Expectations of performance
timeFrame: From collection of baseline data on day one to the end of day two of data collection.
Locations:
city: Canterbury
country: United Kingdom
facility: Canterbury Christ Church University
state: Kent
Study officials:
References: