CaffeineNCT04317157
Placebo Effects Investigated by Different Experimental Designs
A study testing Caffeine in people with Caffeine and Placebo, run by University of Sao Paulo at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- What is being tested?
- Caffeine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteBrazil
- Study dates
- Jan 2022to Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects
- Must be able to swallow pills
- Must be able to perform isometric knee extension
Who cannot join
- Subjects with motor impairments
Trial locations and contacts
1 site in 1 country.
Brazil1 site
School of Arts, Sciences and Humanities - University of São Paulo
São Paulo, 03828-000
Flavio O Pires, PhD, +55+11+995335777, piresfo@usp.br
About this study
Official title: Placebo Effects and Physical Performance: Central and Peripheral Mechanisms Investigated by Different Experimental Designs
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.
Read the 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.
- Being tested
- Caffeine, Placebo
- Keywords
- Randomized clinical trial, Expectancy, Placebo, Caffeine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDietary supplement
Specific dosage of caffeine for each participant (6 mg.kg-1).
PlaceboOther
Placebo pill.
| Study group | Role | What they receive |
|---|---|---|
| Caffeine Clinical Trial | Experimental | Participants will ingest 6 mg.kg-1 of caffeine ~45 minutes before the trial, in a double-blinded, randomized clinical trial fashion. Receives: Other: Placebo |
| Placebo Clinical Trial | Placebo comparator | Participants will ingest placebo ~45 minutes before the trial, in a double-blinded, randomized clinical trial fashion. Receives: Other: Placebo |
| Placebo-deceived Caffeine | Experimental | Participants will be lead to believe that they are ingesting 6 mg.kg-1 of caffeine ~45 minutes before the trial. Receives: Other: Placebo |
| Placebo-deceived Placebo | Placebo comparator | Participants will be informed they are ingesting placebo ~45 minutes before the trial. Receives: Other: Placebo |
| Control-Caffeine | Active comparator | Participants will be informed they are ingesting 6 mg.kg-1 of caffeine ~45 minutes before the trial. Receives: Dietary Supplement: Caffeine |
| Control | No intervention | Participants will perform a baseline trial with no intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
Measured: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
Measured: Throughout the exercises performed 30 minutes before the intervention and up to 60 minutes after the intervention
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.
Measured: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
Measured: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
Measured: 30 minutes before the intervention and up to 60 minutes after the intervention
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).
Measured: Throghout the isometric contraction 30 minutes before the intervention and up to 60 minutes after the intervention
Secondary outcomes (1)
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).
Measured: Throughout the isometric contraction 30 minutes before the intervention and up to 60 minutes after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2020
- Study startJan 2022 (estimated)
- Primary completionJul 2022 (estimated)
- Study completionAug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CaffeineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Newcastle University
- Responsible party
- Principal investigator, Flavio de Oliveira Pires, University of Sao Paulo
- Investigators
- Flavio O Pires, Phd, Principal investigator, School of Arts, Sciences and Humanities - University of São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04317157
- Sponsor's protocol ID
- USP-NorthumbriaUNI
- Status last verified
- Jun 2021
- First submitted
- 9 Mar 2020
- Last updated
- 15 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 30114971Pires 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.
PubMed 30246799
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo Effects and Physical Performance: Central and Peripheral Mechanisms Investigated by Different Experimental Designs
- ClinicalTrials.gov ID
- NCT04317157
- Acronym / sponsor ID
- USP-NorthumbriaUNI
- Keywords
- Randomized clinical trial, Expectancy, Placebo, Caffeine
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Newcastle University
- Study start
- Jan 2022 (estimated)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Aug 2022 (estimated)
- First posted
- 23 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
- 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.
| Arm | Type | Receives |
|---|---|---|
| Caffeine Clinical Trial | Experimental | Other: PlaceboParticipants will ingest 6 mg.kg-1 of caffeine ~45 minutes before the trial, in a double-blinded, randomized clinical trial fashion. |
| Placebo Clinical Trial | Placebo comparator | Other: PlaceboParticipants will ingest placebo ~45 minutes before the trial, in a double-blinded, randomized clinical trial fashion. |
| Placebo-deceived Caffeine | Experimental | Other: PlaceboParticipants will be lead to believe that they are ingesting 6 mg.kg-1 of caffeine ~45 minutes before the trial. |
| Placebo-deceived Placebo | Placebo comparator | Other: PlaceboParticipants will be informed they are ingesting placebo ~45 minutes before the trial. |
| Control-Caffeine | Active comparator | Dietary Supplement: CaffeineParticipants will be informed they are ingesting 6 mg.kg-1 of caffeine ~45 minutes before the trial. |
| Control | No intervention | –Participants will perform a baseline trial with no intervention. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy subjects
- Must be able to swallow pills
- Must be able to perform isometric knee extension
Key exclusion criteria (1 listed)
- Subjects with motor impairments
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CaffeineSpecific dosage of caffeine for each participant (6 mg.kg-1). | Dietary supplement | Control-Caffeine |
| PlaceboPlacebo pill. | Other | Caffeine Clinical Trial, Placebo Clinical Trial, Placebo-deceived Caffeine, Placebo-deceived Placebo |
Primary outcome
Torque change
Time frame: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
Rate of force development change
Time frame: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
Muscle activity change
Time frame: Throughout the exercises performed 30 minutes before the intervention and up to 60 minutes after the intervention
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.
H-reflex change
Time frame: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
M-wave change
Time frame: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
V-wave change
Time frame: 30 minutes before the intervention and up to 60 minutes after the intervention
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.
Motor related cortical potential change
Time frame: Throghout the isometric contraction 30 minutes before the intervention and up to 60 minutes after the intervention
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).
1 secondary outcome
Ratings o perceived exertion change
Time frame: Throughout the isometric contraction 30 minutes before the intervention and up to 60 minutes after the intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2021.
- Background: PubMed 30114971Beedie 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.
- Results publication: PubMed 30246799Pires 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flavio O Pires, Phd principal investigator
School of Arts, Sciences and Humanities - University of São Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Caffeine in people with Caffeine and Placebo, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Flavio O Pires, PhD (+55+11+995335777, piresfo@usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Torque change (time frame: 30 minutes before the intervention and up to 60 minutes after the intervention). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04317157, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2021.