Clinical trial NCT04317157: Placebo Effects Investigated by Different Experimental Designs
Official title: Placebo Effects and Physical Performance: Central and Peripheral Mechanisms Investigated by Different Experimental Designs
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Caffeine
Placebo
Baseline
Keywords: Randomized clinical trial
Expectancy
Placebo
Caffeine
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Newcastle University
First posted: 2020-03-23
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: There are five experimental conditions in a crossover design. Participants will receive placebos in four of these trials and caffeine in the other one.
Primary purpose: BASIC_SCIENCE

Brief summary: This study aims to investigate the neurophysiological mechanisms of placebo perceived as caffeine during a motor task. Central and peripheral measures (i.e. electroencephalography and electromyography) will be assessed.

Detailed description: Classical randomized clinical trial (RCT) controlled by a placebo is considered as the gold-standard design when evaluating the efficacy of drugs and interventions, as a given treatment is scientifically sound only if it is superior to placebo. One of strongest threats to placebo is that a double-blinded RCT could not completely neutralize every human consciousness-distorted reality; behavioral aspects such as the belief on a given treatment may directly result in different placebo effects and produce different treatment placebo effect sizes. Any patient may create his/her own expectation on a situation having a chance of 50% placebo vs 50% treatment depending on the available information; beliefs may impact on working mechanism of pharmacological treatments, but also on placebos. One alternative emerged from debates by different scientific fields; the control for the participant's expectancy by using an active substance-perceived placebo. When compared to a traditional double-blinded placebo-controlled RCT design, the placebo-deceived design has the advantage of controlling expectation and anxiety biases in treatments having combined pharmacological and psychological effects, despite some obvious limitation.

Mechanisms underpinning the ergogenic effect of placebos are unclear, but the suggestion is that the expectancy in using an ergogenic treatment/substance leads to psychobiological changes comparable to the actual treatment. A question that arises over RCT designs is how much effect on physical performance can be attributed to the actual substance and how much to the expectancy of receiving the actual substance. This question is relevant, as clinical and exercise settings have used double-blinded placebo-controlled RCT designs to investigate the ergogenic aids effects and mechanisms. However, participants may experience different placebo effect sizes in a double-blinded RCT design. This study will investigate ergogenic placebo effects and mechanisms elicited by double-blinded placebo-controlled RCT and deceived-placebo designs.

This crossover study will investigate two different experimental designs. During the traditional double-blind RCT, participants will be informed that they will be randomly assigned to caffeine and placebo sessions, thereby having 50% placebo chances vs 50% caffeine chances. However, they will receive placebo capsules in both RCT sessions (non-informed substance/received placebo). In contrast, they will be precisely informed about their allocation (either caffeine or placebo trial) in the deceived-placebo design, however they will ingest placebo capsules in both sessions (informed caffeine/received placebo vs informed placebo/received placebo), thereby controlling caffeine pharmacological effects. A true caffeine trial (informed caffeine/received caffeine 6 mg·kg-1) will be performed as a positive control in the last session.

Eligibility criteria: Inclusion Criteria:

* Healthy subjects
* Must be able to swallow pills
* Must be able to perform isometric knee extension

Exclusion Criteria:

* Subjects with motor impairments

Primary outcomes:
measure: Torque change
timeFrame: 30 minutes before the intervention and up to 60 minutes after the intervention
measure: Rate of force development change
timeFrame: 30 minutes before the intervention and up to 60 minutes after the intervention
measure: Muscle activity change
timeFrame: Throughout the exercises performed 30 minutes before the intervention and up to 60 minutes after the intervention
measure: H-reflex change
timeFrame: 30 minutes before the intervention and up to 60 minutes after the intervention
measure: M-wave change
timeFrame: 30 minutes before the intervention and up to 60 minutes after the intervention
measure: V-wave change
timeFrame: 30 minutes before the intervention and up to 60 minutes after the intervention
measure: Motor related cortical potential change
timeFrame: Throghout the isometric contraction 30 minutes before the intervention and up to 60 minutes after the intervention
Secondary outcomes:
measure: Ratings o perceived exertion change
timeFrame: Throughout the isometric contraction 30 minutes before the intervention and up to 60 minutes after the intervention
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: School of Arts, Sciences and Humanities - University of São Paulo
Study officials:
affiliation: School of Arts, Sciences and Humanities - University of São Paulo
name: Flavio O Pires, Phd
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beedie C, Benedetti F, Barbiani D, Camerone E, Cohen E, Coleman D, Davis A, Elsworth-Edelsten C, Flowers E, Foad A, Harvey S, Hettinga F, Hurst P, Lane A, Lindheimer J, Raglin J, Roelands B, Schiphof-Godart L, Szabo A. Consensus statement on placebo effects in sports and exercise: The need for conceptual clarity, methodological rigour, and the elucidation of neurobiological mechanisms. Eur J Sport Sci. 2018 Nov;18(10):1383-1389. doi: 10.1080/17461391.2018.1496144. Epub 2018 Aug 16.
citation: Pires FO, Dos Anjos CAS, Covolan RJM, Fontes EB, Noakes TD, St Clair Gibson A, Magalhaes FH, Ugrinowitsch C. Caffeine and Placebo Improved Maximal Exercise Performance Despite Unchanged Motor Cortex Activation and Greater Prefrontal Cortex Deoxygenation. Front Physiol. 2018 Aug 17;9:1144. doi: 10.3389/fphys.2018.01144. eCollection 2018.