Clinical Research Directory

Does Caffeine Facilitate Human Reward Learning Behaviors?

"Learning from the rewards" is underlying the formulation of knowledge and habits in daily life. Caffeine is the most commonly used "psychoactive" substance that could change one's mind state by affecting the brain and nervous system. By such effects, caffeine enhances reward signals - dopamine - in human brains. In this research study, we will find out whether taking caffeine acutely or daily can enhance reward learning processes.

Effects of Caffeine Ingestion on Morning Cognitive and Muscle Repeated Sprint Performance in Males

Athletes often compete in the morning when they are biologically weaker; normally in competition heats or quarterfinals to qualify for the finals scheduled in the evening. Some athletes may even choose to perform at submaximal levels in these qualifying rounds, especially when they are expected to perform multiple times in the same day (such as weightlifting at the Olympic Games). Gross muscular performance such as power output or force production is greater in the evening than the morning (\~3-14% variation). Similarly, time-trial performance and repeated sprint performance (RSP; a good measure of performance in team sport) is \~3 and 5 % greater in the evening than the morning. The reason for this daily variation in performance is attributed to central factors (such as the body clock), as well as motivational and peripheral factors, including higher core and muscle temperatures in the evening compared to the morning. The body clock located within the anterior hypothalamus consists of a group of neurons known as suprachiasmatic nuclei, which are responsible for controlling the rhythm of core temperature. This 'master clock' has an endogenous period (\~24.2 h) slightly longer than the 24-h solar day; therefore, must be entrained by time cues (zeitgebers) to remain in sync with the environment, of these the light-dark cycle is the most powerful in humans. The most efficient nutritional ergogenic is caffeine. Recently caffeine has been investigated to reduce the negative influence of diurnal variations on repeated-sprint ability test (10 × 6 s cycle sprints, with 30 s of rest) at 60 min after ingestion of either 5 mg·kg-1 or placebo. A recent study reported that caffeine supplementation did not prevent the reduction in performance in the morning. However, placebo effect can be 3-5% and hence the use of a No-pill condition would ensure that any placebo effect is accounted for and that the true potential effect of caffeine can be established. To the best of our knowledge, no study has yet investigated a) caffeine (300 mg), NoPill or Placebo (300 mg dextrose) effects on cognitive and physiological morning performance.

Effects of Caffeine Ingestion on Morning Cognitive and 4-km Time Trial Performance in Males

Athletes often compete in the morning when they are biologically weaker; normally in competition heats or quarterfinals to qualify for the finals scheduled in the evening. Some athletes may even choose to perform at submaximal levels in these qualifying rounds, especially when they are expected to perform multiple times in the same day (such as weightlifting at the Olympic Games). Gross muscular performance such as power output or force production is greater in the evening than the morning (\~3-14% variation). Similarly, time-trial performance and repeated sprint performance (RSP; a good measure of performance in team sport) is \~3 and 5 % greater in the evening than the morning. The reason for this daily variation in performance is attributed to central factors (such as the body clock), as well as motivational and peripheral factors, including higher core and muscle temperatures in the evening compared to the morning. The body clock located within the anterior hypothalamus consists of a group of neurons known as suprachiasmatic nuclei, which are responsible for controlling the rhythm of core temperature. The most efficient nutritional ergogenic is caffeine. Recently caffeine has been investigated to reduce the negative influence of diurnal variations on repeated-sprint ability test (10 × 6 s cycle sprints, with 30 s of rest) at 60 min after ingestion of either 5 mg·kg-1 or placebo. Lopes-Silva et al. (2019) reported that caffeine supplementation did not prevent the reduction in performance in the morning. However, placebo effect can be 3-5% and hence the use of a No-pill condition would ensure that any placebo effect is accounted for and that the true potential effect of caffeine can be established. To the best of our knowledge, no study has yet investigated caffeine (CAFF), NoPill (NOPILL) or Placebo (PLAC) effects on cognitive and 4-km time-trial (TT) performance. As a diurnal variation in 4-km TT has been widely reported in a similar population. The aim of the present study is to investigate if ingesting caffeine on the day of the morning test, to improve performance.

Caffeine for Infants Born at 28 to 34 Weeks Receiving Respiratory Support

The goal of this pilot clinical trial is to test if it is possible to conduct a larger study on the use of caffeine in preterm infants who need help with their breathing. It will also look at whether caffeine helps these infants get healthy enough to leave the hospital sooner. The main questions the researchers aim to answer are: Can the investigators successfully recruit and keep enough participants in the study? Do the medical teams follow the study drug instructions correctly? Does caffeine reduce the total time infants spend in the Neonatal Intensive Care Unit (NICU)? Researchers will compare caffeine to a placebo (a look-alike substance with no active medicine) to see if caffeine is a helpful treatment for babies born between 28 and 34 weeks of gestation who are using a breathing machine or oxygen. Participants will: Be randomly assigned to receive either caffeine or a placebo through an IV or a feeding tube. Receive the study treatment once a day as long as they require respiratory support (and for 24 hours after they stop). Be monitored by the research team for clinical outcomes like feeding progress, breathing stability, and growth until they are discharged from the hospital.

Effects of Variations in Caffeinated Beverages on Well-being

This study will evaluate post-beverage subjective caffeine responses and physiological responses to caffeinated beverage variations in generally healthy adults.

Caffeine Strategies and Fat Oxidation

The goal of this clinical trial is to learn if different forms of caffeine ingestion can influence fat oxidation during submaximal cycling exercise. The study will recruit healthy adults, both men and women, aged 18 to 50, who regularly perform aerobic exercise. The main questions it aims to answer are: * Does caffeine increase fat oxidation during one hour of cycling at the Fatmax intensity? * Do different forms of caffeine ingestion (capsule, coffee, chewing gum, or mouth rinse) differ in their effect on fat oxidation? * Do these caffeine forms alter total energy expenditure, cardiorespiratory response, or perceived exertion during exercise? * Are there differences in the occurrence or severity of side effects between caffeine administration methods? Researchers will compare each caffeine form to its corresponding placebo to determine their effects on fat oxidation and other physiological outcomes. Participants will: * Attend a pre-experimental session to determine their Fatmax intensity and VO₂max using an incremental cycling test * Perform eight experimental sessions, each consisting of one hour of cycling at Fatmax intensity * Receive caffeine or placebo via capsules, coffee, chewing gum, or mouth rinse according to a randomized, double-blind, crossover design * Be monitored for fat and carbohydrate oxidation, total energy expenditure, heart rate, and perceived exertion during exercise * Report any side effects immediately after the session and 24 hours later using a structured questionnaire All sessions will be conducted under controlled laboratory conditions with standardized protocols to ensure safety and reliable measurements.

Effects of Caffeinated Beverages on Well-being

This study will evaluate post-beverage subjective caffeine responses and physiological responses to caffeinated beverages in generally healthy adults.

Caffeine Optimization Versus Standard Caffeine Dosage (2B-2)

This clinical trial will be a comparison between personalized recommended caffeine dosing regimen versus the standard recommended caffeine dosing regimen for sustaining performance during sleep deprivation and minimizing side effects and subsequent sleep disruption. The questions this study aims to answer are: Whether the personalized caffeine recommendations improve vigilance, sleepiness, and cognition after total sleep deprivation, compared to standard recommendations; Whether the personalized caffeine recommendation better addresses the physical and emotional side effects of total sleep deprivation, compared to standard recommendations; And whether personalized caffeine recommendations aids in better recovery sleep after total sleep deprivation, compared to standard recommendations. Participants will be asked to: 1. Complete a 13-day at-home portion, wearing an actigraph watch to measure activity and sleep, and complete motor vigilance tests up to six times a day. 2. Complete a 4-day in-lab portion, where participants will have to complete one night of baseline sleep, undergo 62-hours of total sleep deprivation, and then complete one night of recovery sleep. 3. During the in-lab portion of the study, participants will be asked to complete more motor vigilance tests. Researchers will be comparing the personalized caffeine recommendation group against the standard caffeine recommendation to see if it is better at addressing each of the main questions.

The Effects of Caffeine on Exercise Physiology and Time-trial Performance in a Hot Environment

Maintaining a stable core temperature is vital for physiological function; yet, exercise in heat can be problematic, and there is risk of exertional heat-related illness (Flouris \& Schlader, 2015; Leyk et al., 2019; Périard et al., 2021; Tyler et al., 2016; Veltmeijer et al., 2015). While aerobic fitness improves heat tolerance (Alhadad et al., 2019), strategies like acclimation and pre-cooling also mitigate heat stress (Casadio et al., 2016; Lorenzo et al., 2010; Ross et al., 2013; Siegel et al., 2010). Caffeine, an ergogenic aid (Del Corso et al., 2011; John et al., 2024), is known to enhance performance via adenosine antagonism and increased catecholamines in normothermic environments (Fredholm et al., 1999; Graham \& Spriet, 1991). However, effects in heat are inconsistent (Ganio et al., 2009; Zhang et al., 2014), possibly due to caffeine reducing the ability to thermoregulate effectively. Therefore, the aim of this study is to investigate the effects of a moderate dose of caffeine (5 mg/kg) on thermoregulation during a 30-minute running time trial in 35°C heat.

The Repeatability of the Effect of Caffeine Supplementation on Submaximal Physiological Responses and Cycling Time Trial Performance

Recently, Grgic (2018) discussed the concept of responders and non-responders to caffeine supplementation highlighting the importance of the repeatability of results. However, the number of studies that have investigated this idea by repeating the same time-trial performance test multiple times with the same caffeine dose is sparse (Astorino et al., 2012; Del Coso et al., 2019). Furthermore, studies have shown that differences in the CYP1A2 genotype may account for some of the variation in time-trial performance (Guest et al., 2018). Thus, the current study aims to identify whether the effects of moderate caffeine supplementation (5 mg/kg) on time-trial performance are repeatable to aid the identification of responders and non-responders. Additionally, the study aims to determine if the CYP1A2 genotype may explain any of the variability in time-trial performance in trained male cyclists.

The Caffeine Therapy in the Fetal to Neonatal Transition

Introduction: The caffeine is used in the treatment for apnea of prematurity and it has several positive effects in the neurodevelopment of preterm babies. There are innumerable observational studies suggesting that initiating caffeine in the first hours of life may offer more benefits in the reduction of the necessity of intubation and in ventilation time. It is necessary to expand further research on the best time to start caffeine, which may improve the quality of care for premature infants. Objective: To evaluate the benefits of caffeine administration in the first two hours of life compared to administration at 24 hours of life in premature patients on noninvasive mechanical ventilation with birth weights less than 1250 grams. Methodology: Preterm newborn patients with birth weight \< 1250 grams born at Hospital de Clínicas de Porto Alegre who are not intubated in the delivery room will be included. Patients will be randomized into two groups. One arm of the study will receive caffeine at 2 hours of age and the other arm will receive caffeine at 24 hours of age (control). Patients in the control group will receive 0.9% SF at 2 hours of life in order to keep the study blinded. The following outcomes will be evaluated: need for intubation, time on invasive and non-invasive mechanical ventilation, BPD, necrotizing enterocolitis, need for ROP treatment, PDA with hemodynamic repercussions, peri-intraventricular hemorrhage, leukomalacia and death. The sample size calculation is 50 patients, 25 in each arm. Expected Results: It is expected to find a 43% reduction in the need for intubation in preterm infants who receive caffeine in the first two hours of life compared to administration at 24 hours of life. It is also expected to find a reduction in mechanical ventilation time, in addition to a possible reduction in negative outcomes associated with prematurity.

Investigating the Acute and Chronic Effects of a Supplement Containing Caffeine, Vitamins, Minerals and Botanical Extracts on Cognition, Sleep and Wellbeing, in Healthy Volunteers

The aim of the study is to investigate the acute and chronic effects of a supplement containing Caffeine, Vitamins, Minerals and Botanical extracts on cognitive function, sleep and wellbeing, in healthy volunteers. The study will follow a randomised, double-blind, placebo-controlled, crossover design. Participants will receive both treatments, and both study arms will include an acute testing visit (day 1) and a chronic testing visit (day 29). The active treatment contains a blend of 120mg caffeine, vitamins, minerals and botanical extracts and the matched placebo treatment contains marigold extract and brown rice flour. The trial will use computerised cognitive tasks, administered via COMPASS software (Northumbria University, UK), online cognitive assessments via Cognimapp and self-reported questionnaires and sleep diary, as measures of the outcome variables. 90 participants will participate, aged 18-75, and self-ported as being in good health. Participants will be randomly allocated to a treatment order and will be supplied with either the active treatment or the placebo whilst visiting the research centre for the acute testing visits. Participants will take the treatment home to consume daily for the duration of the supplementation period. Participants will record the time of taking treatment each day in a treatment diary which will be returned to the research centre, along with any unused treatment, at each chronic testing visit.

Effects of Caffeine on Reinforcement Learning in Healthy Adults Using PET/MRI

This research study aims to determine whether and how caffeine intake affects learning process through reward feedback compared to placebo. The data acquired from this study would improve our understanding on the consequence and mechanism of caffeine intake in the aspect of learning process. Participants will perform a reinforcement learning task (i.e. Probabilistic Selection Task) and a motor inhibition task (i.e. Go/NoGo task) in a brain scan. The scan will be done with the Siemens Biograph mMR positron emission tomography (PET)/ magnetic resonance imaging (MRI) 3 Tesla scanner. The PET allows us to see the changes in the "reward signals" - dopamine - in the brain using a radioactive dye called \[11C\]Raclopride. The MRI, on the other hand, enables us to take detailed pictures of the brain activities during cognitive tasks using a high-powered magnet. Reviewing these pictures will help us understand the influence of caffeine on reward signals and brain activities during the learning process.