ADoRe: Does Caffeine Facilitate Human Reward Learning Behaviors?

Sponsor
Yu-Shiuan Lin (Other)
Overall Status
Recruiting
CT.gov ID
NCT05325502
Collaborator
(none)
36
1
3
7.9
4.6

Study Details

Study Description

Brief Summary

"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.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: caffeine
  • Dietary Supplement: mannitol
N/A

Detailed Description

Reward learning is associated with the formulation of habits, memories, and beliefs. Positive (receiving an unexpected reward) and negative reinforcement (eliminating an unwanted state) learning are primarily modulated by striatal dopamine D1 and D2 receptors. While caffeine, a psychostimulant regularly consumed by 80% worldwide population, is known to facilitate striatal dopamine signaling, the potential of caffeine on enhancing reward learning in humans remains unknown.

In this double-blind, randomized, crossover study, 36 young healthy non-smoking habitual caffeine consumers (daily dose 100 - 450 mg) who are aged between 18 and 40 will be examined. Each of the 36 participants (18 F, 18 M) will undergo an acute caffeine condition, a daily caffeine condition, and a daily placebo condition. Each condition consists of 7 days - 6 ambulatory days followed by 1 laboratory visit.

In the ambulatory part, participants will abstain from caffeine, nicotine, medications, and recreational drugs. Compliance to the interventions and abstinence of caffeine will be monitored by salivary caffeine concentration every day. Bedtime and sleep quality will be recorded in sleep diary. On the laboratory visit, participants will perform cognitive tasks on a 2.5h task battery, which includes a probabilistic selection task, a motor inhibition task, and a salience attribution test. We also measure their arousal and anxiety levels 1h after the second intake on the laboratory visit.

We will use Bayes factor analyses to test our confirmatory hypotheses (on the primary outcomes): 1) Caffeine enhances the accuracy of reward learning; 2) Daily intake of caffeine facilitates the negative reinforcement compared to acute its intake. On the secondary outcomes, we examine the exploratory hypotheses that caffeine enhances motor inhibition and motivational salience. Arousal and anxiety levels will be examined as a covariate which potentially contribute to the caffeine-induced changes in reward learning performance.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
36 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
Caffeine and Reward Learning: Characterizing Behavioral Expression of Adenosine-Dopamine Interaction
Actual Study Start Date :
May 5, 2022
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

7 days placebo intake.

Dietary Supplement: mannitol
two doses per day: 200 mg in the morning & 100 mg in the afternoon

Active Comparator: Acute caffeine

6 days placebo followed by 1 day caffeine intake.

Dietary Supplement: caffeine
two doses per day: 200 mg caffeine in the morning; 100 mg caffeine in the afternoon

Dietary Supplement: mannitol
two doses per day: 200 mg in the morning & 100 mg in the afternoon

Experimental: Daily caffeine

7 days caffeine intake

Dietary Supplement: caffeine
two doses per day: 200 mg caffeine in the morning; 100 mg caffeine in the afternoon

Outcome Measures

Primary Outcome Measures

  1. The accuracy (% of correct answers) in implicit learning through different probabilities of monetary reward feedback [1-hour after the second intake on the 7th day]

    Through a probabilistic selection task, participant will go through a training phase to learn the rules which options may be more likely to return monetary feedback, and the knowledge learned will be tested in a second phase where the task difficulty is increased, and no feedback is provided. The overall accuracy in the testing phases will be examined, as well as the accuracies in choosing or avoiding the highest and lowest reward-probability stimuli.

Secondary Outcome Measures

  1. The errors in motor inhibition (rates of false alarm) in a motor inhibition task [1.5-hour after the second intake on the 7th day]

    Through a reaction-inhibition task (Go/NoGo), participants will go through two phases of the task: 1) Only respond to a specific stimulus when it shows; 2) Respond to all stimuli except for the specific stimulus. The accuracy in motor inhibition will be indicated by the errors made in the no-go signals (i.e. false alarm).

  2. Salience attribution behaviors [1.5-hour after the second intake on the 7th day]

    subjective perception towards the probabilities (0 -100%) of reward feedback from each choice in the probabilistic selection task.

Other Outcome Measures

  1. Self-report anxiety levels [1-hour after the second intake on the 7th day]

    State-Trait Anxiety Inventory for Adults (STAI-A) is used to examine the subjective anxiety levels in general as a trait (20 questions) and as a current state (20 questions). Participants will rate the levels using a Likert's scale (For trait - 0: Almost never, 1: Sometimes, 2: Often, 3: Almost always; For current state - 0: not at all, 1: Somewhat, 2: Moderately so, 3: Very much so).

  2. Subjective sleepiness and alertness [1-hour after the second intake on the 7th day]

    Self-report one-question Karolinska Sleepiness Scale is used to rate the subjective sleepiness/alertness from 1 (very awake), 3 (awake), 5 (neither awake or tired), 7 (tired but no problem to stay awake), to 9 (very tired, big problem to stay awake, struggling with sleep), and 2, 4, 6, 8 for intermediate levels.

  3. heart rate measurement [1-hour after the second intake on the 7th day]

    heart rates (per min)

  4. blood pressure measurement [1-hour after the second intake on the 7th day]

    systolic and diastolic blood pressure

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 40 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Age ≥ 18 and ≤ 40

  • Clinically healthy

  • Non-smokers

Exclusion Criteria:
  • Habitual caffeine intake < 100 mg or > 450 mg

  • Pregnant or lactating women

  • Women using hormonal contraceptives

  • BMI < 18.5 or > 29.9

  • Sleep disturbance or extreme chronotypes

  • Nicotine or recreational drug users

  • Depression, anxiety, psychosis, or neurologic disorders

  • Severe heart or cardiovascular diseases

  • Diabetes or metabolic diseases

  • Under chronic medications

  • Incapable to operate the tasks or comprehend the study information in German or English

  • Users of the Bopomo alphates utilized as stimuli in the reward learning tasks

  • Current enrolment in other clinical trials

Contacts and Locations

Locations

Site City State Country Postal Code
1 Centre for Chronobiology, University Psychiatric Clinics Basel Basel Basel City Switzerland CH-4002

Sponsors and Collaborators

  • Yu-Shiuan Lin

Investigators

  • Principal Investigator: Yu-Shiuan Lin, PhD, Centre for Chronobiology, University Psychiatric Clinics Basel

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Yu-Shiuan Lin, Postdoc researcher, Centre for Chronobiology
ClinicalTrials.gov Identifier:
NCT05325502
Other Study ID Numbers:
  • CChronobiology
First Posted:
Apr 13, 2022
Last Update Posted:
May 26, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 26, 2022