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

NCT06763172 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: IRB2022P0016811R21MH138923-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy; Caffeine; Adenosine; Dopamine D2/3 Receptor Availability

Keywords

PET/fMRI

Outcome Measures

Primary Outcomes (2)

• Dopamine D2/D3 receptor availability

  Dopamine D2/D3 receptor availability will be measured and indexed by the \[11C\]Raclopride nondisplaceable binding potential (BPND).

  During the PET/fMRI scan on the study day

• Effects of caffeine on reinforcement learning assessed by Probabilistic Selection Task (PST) in fMRI

  Reinforcement learning and the associated brain activity will be measured using PST in a fMRI scan. The reinforcement learning is indexed by the accuracy of the task performance on the behavioral level and the hemodynamic response to reward feedback on the neural level.

  During the PET/fMRI scan on the study day

Secondary Outcomes (2)

• Effects of caffeine on motor inhibition assessed by a Go/NoGo task in fMRI

  During the PET/fMRI scan on the study day

• Effects of caffeine on salience measured by Salience Attribution Test (SAT)

  After the PET/fMRI scan on the study day

Other Outcomes (4)

• Effects of caffeine on cerebral blood flow

  During the PET/fMRI scan on the study day

• Effects of caffeine on subjective sleepiness as measured by Karolinska Sleepiness Scale (KSS)

  After the PET/fMRI scan on the study day

• Effects of caffeine on anxiety levels measured by State-Trait Anxiety Inventory- adult version (STAI-A)

  After the PET/fMRI scan on the study day

Study Arms (2)

Caffeine

EXPERIMENTAL

Caffeine tablet, 200mg

Drug: Caffeine (200 mg)

Placebo

PLACEBO COMPARATOR

Lactose tablet

Drug: Placebo

Interventions

Caffeine (200 mg) DRUG

Caffeine (200mg) will be administered per os 20 minutes prior to the PET/fMRI data acquisition.

Caffeine

Placebo DRUG

Lactose tablet will be administered per os 20 minutes prior to the PET/fMRI data acquisition.

Also known as: Lactose

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥ 18 and ≤ 45.
• Habitual caffeine intake ≥ 100 mg and ≤ 450 mg daily.
• Non-smokers.
• Clinically healthy.
• Have normal vision or corrected to normal vision.

You may not qualify if:

• Pregnant or lactating women.
• Women using hormonal contraceptives.
• BMI \< 18.5 or \> 29.9
• Sleep disturbance or extreme chronotype.
• Urine test positive on one of the following substances: benzoylecgonine, morphine, d-Methamphetamine, d-Amphetamine, Benzodiazepines, Secobarbital, Methadone, Buprenorphine Glucuronide, Nortriptyline, MDMA, Oxycodone, PCP, Propoxyphene, and Cannabis/THC
• Diagnosis of depression, anxiety, psychosis, or neurologic disorders in the last 5 years.
• Heart or cardiovascular diseases.
• Diabetes or other metabolic diseases.
• Under chronic medications, for instance, painkiller and steroid.
• Allergy to lactose (main ingredient of blank control dose)
• Incapable to operate the tasks or comprehend the study information in English.
• Metallic foreign bodies such as cardiac pacemakers, perfusion pumps, aneurysm clips, metallic tattoos anywhere on the body, tattoos near the eye.
• Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions
• Inability to lie flat on scanner bed for about 90 min as assessed by physical examination and medical history (e.g. arthritis)
• Recent exposure to radiation (i.e., PET from other research studies) that, when combined with this study, would be above the allowable limits

Sponsors & Collaborators

• Hsiao-Ying Wey: lead

Study Sites (1)

Athinoula A. Martinos Center for Biomedical Imaging

Charlestown, Massachusetts, 02129, United States

RECRUITING

Related Publications (6)

• Bedingfield JB, King DA, Holloway FA. Cocaine and caffeine: conditioned place preference, locomotor activity, and additivity. Pharmacol Biochem Behav. 1998 Nov;61(3):291-6. doi: 10.1016/s0091-3057(98)00092-6.

  PMID: 9768563 BACKGROUND

• Moran EK, Culbreth AJ, Kandala S, Barch DM. From neuroimaging to daily functioning: A multimethod analysis of reward anticipation in people with schizophrenia. J Abnorm Psychol. 2019 Oct;128(7):723-734. doi: 10.1037/abn0000461. Epub 2019 Aug 29.

  PMID: 31464449 BACKGROUND

• Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Wong C, Ma J, Pradhan K, Tomasi D, Thanos PK, Ferre S, Jayne M. Sleep deprivation decreases binding of [11C]raclopride to dopamine D2/D3 receptors in the human brain. J Neurosci. 2008 Aug 20;28(34):8454-61. doi: 10.1523/JNEUROSCI.1443-08.2008.

  PMID: 18716203 BACKGROUND

• Kaasinen V, Aalto S, Nagren K, Rinne JO. Dopaminergic effects of caffeine in the human striatum and thalamus. Neuroreport. 2004 Feb 9;15(2):281-5. doi: 10.1097/00001756-200402090-00014.

  PMID: 15076753 BACKGROUND

• Volkow ND, Wang GJ, Logan J, Alexoff D, Fowler JS, Thanos PK, Wong C, Casado V, Ferre S, Tomasi D. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain. Transl Psychiatry. 2015 Apr 14;5(4):e549. doi: 10.1038/tp.2015.46.

  PMID: 25871974 BACKGROUND

• Ferre S, Bonaventura J, Tomasi D, Navarro G, Moreno E, Cortes A, Lluis C, Casado V, Volkow ND. Allosteric mechanisms within the adenosine A2A-dopamine D2 receptor heterotetramer. Neuropharmacology. 2016 May;104:154-60. doi: 10.1016/j.neuropharm.2015.05.028. Epub 2015 Jun 4.

  PMID: 26051403 BACKGROUND

MeSH Terms

Interventions

Caffeine; Lactose

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Central Study Contacts

Hsiao-Ying Wey, PhD

CONTACT

6177241384; hsiaoying.wey@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: December 31, 2024
• First Posted: January 8, 2025
• Study Start: May 17, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available at the end of the NIMH grant (anticipated 1/1/2027). Data and the code/software/tools used to develop the published or submitted dataset will be shared at the time of data submission or publication and maintained for no shorter than 5 years.

Locations

US (1)