Placebo Effects Investigated by Different Experimental Designs

Caffeine Clinical Trial

Official title:

Placebo Effects and Physical Performance: Central and Peripheral Mechanisms Investigated by Different Experimental Designs

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04317157
• Other study ID #: USP-NorthumbriaUNI
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2022
• Est. completion date: August 2022

Study information

• Verified date: June 2021
• Source: University of Sao Paulo
• Contact: Flavio O Pires, PhD
• Phone: +55+11+995335777
• Email: piresfo[@]usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: August 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy subjects

• Must be able to swallow pills

• Must be able to perform isometric knee extension

Exclusion Criteria:

• Subjects with motor impairments

Related Conditions & MeSH terms

• Baseline
• Caffeine
• Placebo

Intervention

Dietary Supplement:
• Caffeine
Specific dosage of caffeine for each participant (6 mg.kg-1).

Other:
• Placebo
Placebo pill.

Locations

Country	Name	City	State
Brazil	School of Arts, Sciences and Humanities - University of São Paulo	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Newcastle University

Country where clinical trial is conducted

Brazil, 

References & Publications (2)

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. — View Citation

Pires FO, Dos Anjos CAS, Covolan RJM, Fontes EB, Noakes TD, St Clair Gibson A, Magalhães FH, Ugrinowitsch C. Caffeine and Placebo Improved Maximal Exercise Performance Despite Unchanged Motor Cortex Activation and Greater Prefrontal Cortex Deoxygenation. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Torque change	Knee extension torque (N·m) will be recorded during a maximal voluntary contraction through a load cell (EMG System ®, São José dos Campos, Brazil) coupled to a custom-built knee extension chair. Participants will have their torso individually adjusted on a backrest, in a comfortable position, fixed with straps to avoid body movement.	30 minutes before the intervention and up to 60 minutes after the intervention
Primary	Rate of force development change	Rate of force development (N·m/s) will be recorded during a maximal voluntary contraction through a load cell (EMG System ®, São José dos Campos, Brazil) coupled to a custom-built knee extension chair. Participants will have their torso individually adjusted on a backrest, in a comfortable position, fixed with straps to avoid body movement.	30 minutes before the intervention and up to 60 minutes after the intervention
Primary	Muscle activity change	Vastus lateralis and vastus medialis muscles electromyography (EMG; (mV) will be assessed throughout both the exercises (maximal voluntary contraction and submaximal isometric voluntary contraction) according to standard recommendation.	Throughout the exercises performed 30 minutes before the intervention and up to 60 minutes after the intervention
Primary	H-reflex change	H-reflex (mV) will be recorded at 10 s intervals through wireless electrodes placed over the vastus lateralis and vastus medialis muscles at rest, being considered as the peak-to-peak amplitude.	30 minutes before the intervention and up to 60 minutes after the intervention
Primary	M-wave change	M- and (mV) will be recorded at 10 s intervals through wireless electrodes placed over the vastus lateralis and vastus medialis muscles at rest, being considered as the peak-to-peak amplitude.	30 minutes before the intervention and up to 60 minutes after the intervention
Primary	V-wave change	V-wave (mV) and V-wave/Mmax (a.u.) will be recorded at 10 s intervals through wireless electrodes placed over the vastus lateralis and vastus medialis muscles at rest, being considered as the peak-to-peak amplitude.	30 minutes before the intervention and up to 60 minutes after the intervention
Primary	Motor related cortical potential change	Will be recorded at Fz, Cz, Pz, C1 and C2 positions (µV) by using an electroencephalogram (EEG); the EEG recorded during the EMG burst (from 2 s before up to 4 s after the EMG onset) will be used to calculate the EEG amplitude (µv) in 4 windows within the muscle contraction such as; readiness potential (-1,5 to 0 s), muscle contraction 1 (0 to 1 s), muscle contraction 2 (1 to 2 s) and recovery (3 to 4 s).	Throghout the isometric contraction 30 minutes before the intervention and up to 60 minutes after the intervention
Secondary	Ratings o perceived exertion change	Ratings of perceived exertion (RPE) will be obtained through a category-ratio (CR-10) Borg scale (u.a.). Participants will be familiarized with the scale anchors having the maximal voluntary contraction test as maximal effort template. The scale range from 0 - 10 reflecting the exerted effort (i.e. 0 for nothing at all and 10 extremely strong effort).	Throughout the isometric contraction 30 minutes before the intervention and up to 60 minutes after the intervention