Acute and Chronic Effect of 250 mg Citicoline Consumption on Attention in Adults: A Randomized Trial

The primary study objectives are to test whether among a sample of healthy adults consuming: (1) a single capsule containing 250 mg citicoline has an effect on attentional performance 1, 2 and 3 h post-dose compared to placebo (acute effect), and (2) capsule containing 250 mg citicoline per day for 28 consecutive days has an effect on attentional performance compared to placebo (chronic effect).

Study Overview

• Status: Completed
• Conditions: Attention
• Intervention / Treatment: Dietary supplement: Active capsule; Other: Placebo capsule

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Athens, Georgia, United States, 30602
      • University of Georgia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-pregnant, non-lactating females, 18-60 years of age
• Self-report of good health
• Willing to maintain habitual diet, physical activity pattern, and body weight throughout the trial
• Willing to maintain current dietary supplement use (e.g., multi-vitamin or other supplements approved by investigator, stimulants excluded) throughout the 28 days of the trial. On test days, participant agrees not to take any of their usual dietary supplements until dismissal from University of Georgia.
• Willing to abstain from alcohol consumption and avoid vigorous physical activity for 24 h prior to all test visits.
• Absence of health conditions that would prevent fulfillment of study requirements as judged by the Investigator on the basis of medical history.
• Understanding the study procedures and willing to provide informed consent to participate in the study and authorization to release relevant protected health information to the study investigator.

Exclusion Criteria:

• Failure to meet any one of the inclusion criteria
• Potential participant will be excluded if the individual is being paid to do work by Dr. O'Connor, is unwilling to comply with safety instructions (e.g., to wear a face covering) or reports:
• Vision problems that cannot be corrected with glasses or contact lenses
• usual daily consumption of ≥ 500 mg caffeine
• Consumption of caffeine or other stimulants, such as stimulant medication commonly used for ADHD (e.g. Ritalin or Adderall), within 12 h of testing. Prescription medications are allowed as long as they do not interfere with testing.
• Major trauma or major surgical event within 6 months of screening
• Known intolerance, sensitivity or allergy to any ingredients in the study products
• Extreme dietary habits, as judged by the Investigator
• Moderate or higher intensity exercise of 15 or more minutes completed fewer than 3-h prior to a laboratory testing session.
• Consumption of food or caloric drinks fewer than 2-h prior to the laboratory testing session.
• Consumption of supplements, vitamins and multi-vitamins prior to testing on testing days. Participants can take dietary supplements that they have agreed to maintain on testing days after completing the testing visit.
• Any history of a diagnosed psychiatric or neurobehavioral (e.g., ADHD) disorder
• A history of frequent gastrointestinal distress in response to meals or medicine
• History of cancer in the prior two years, except for non-melanoma skin cancer
• Recent history (within 12 months of screening) or strong potential for alcohol or substance abuse. Alcohol abuse is defined as > 14 drinks per week (1 drink=12 oz beer, 5 oz wine, or 1.5 oz distilled spirits).
• Exposure to citicoline within 30 d prior to screening
• Participant has a condition the investigator believes would interfere with his/her ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results or put the person at undue risk
• Increased risk of exposure to COVID-19
• Increased risk of a severe reaction to exposure to COVID-19
• Participation in a PepsiCo study at the University of Georgia for at least 6 months from signing the consent form
• Participation in any clinical trial for at least 30 days from signing the consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 250 mg citicoline; Opaque capsule	Dietary supplement: Active capsule; 1 capsule daily for 28 days
Placebo Comparator: 0 mg citicoline; Opaque capsule matched in appearance to the active capsule	Other: Placebo capsule; 1 capsule daily for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Errors of commission after 28-day consumption (chronic effect)	Attention performance during the Connors Continuous Performance Test- version III (CPT-III)	Post treatment Day 29 minus pre-treatment (baseline Day 1) change scores

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Errors of commission after acute dosing (single dose on Day 1, the first of 28 daily doses)	Attention performance during the (CPT)-III	Change from pre-dose baseline to 1 hour, 2 hours and 3 hours post dose (baseline Day 1)
Errors of omission after acute dosing	Attention performance during the CPT-III	Change from pre-dose baseline to 1 hour, 2 hours and 3 hours post dose (baseline Day 1)
Errors of omission after chronic dosing	Attention performance during the CPT-III	Post treatment Day 29 minus pre-treatment (baseline Day 1) change scores
Reaction time after acute dosing	Attention performance indicator from the CPT-III	Change from pre-dose baseline to 1 hour, 2 hours and 3 hours post dose (baseline Day 1)
Reaction time after chronic dosing	Attention performance indicator from the CPT-III	Post treatment Day 29 minus pre-treatment (baseline Day 1) change scores
For the acute study only, expectation for change in mental task performance associated with consuming one capsule that may contain citicoline	Measured by two item questionnaire, 5 selections each item, from very much worse to very much better than expected mental task performance if assigned to active and if assigned to placebo	Immediately post-dose (baseline Day 1)
For acute study only, sleep behavior the night prior to testing	Questionnaire about number of hours of sleep last night	Upon arrival (baseline Day 1)
For the acute study only, motivation to complete the attention task	Single question, How do you feel right now, rated on visual analog scale (VAS) from 0 (no motivation at all) to 100 (strongest degree of motivation imaginable)	Change from pre-dose baseline to 1 hour, 2 hours and 3 hours post dose immediately prior to tests of attention
For the acute study only, feelings of mental energy and fatigue	6 questions rated by visual analog scale (VAS) from 0 mm (weakest) to 100 mm (strongest) feelings	Immediately prior to the test of attention, change from pre-dose baseline to 1 hour, 2 hours and 3 hours post dose
For the acute study only, mood states (anxiety)	Profile of Mood States (POMS) questionnaire, 30 questions, How do you feel right now, rated 0 (not at all) to 4 (extremely)	Immediately prior to the test of attention, change from pre-dose baseline to 1 hour, 2 hours and 3 hours post dose mood states, immediately prior to tests of attention
For the acute study only, high frequency (HF) and low frequency (LF) domains of heart rate variability, a biomarker of cognitive function, during the tests of attention	Beats per minute via wearable heart rate monitor	Change from pre-dose baseline to 1 hour, 2 hours and 3 hours post dose
For the chronic study only, expectation for change in mental task performance associated with consuming one capsule daily for 28-days that may contain citicoline	Two item questionnaire, 5 selections each item, from very much worse to very much better than expected mental task performance if had been assigned to active and if had been assigned to placebo for 28 days	Change from post-dose baseline Day 1 to Day 29 measured by
For the chronic study only, sleep behavior the night prior to testing	Questionnaire about number of hours of sleep last night	Change from number of hours of sleep the night before baseline Day 1 versus the number of hours of sleep the night before Day 29
For the chronic study only, motivation to complete the attention task	Single question, How do you feel right now, rated on visual analog scale (VAS) from 0 (no motivation at all) to 100 (strongest degree of motivation imaginable)	Change from pre-dose baseline Day 1 to Day 29
For the chronic study only, feelings of mental energy and fatigue	6 questions rated by visual analog scale (VAS) from 0 mm (weakest) to 100 mm (strongest) feelings	Immediately prior to test of attention, change from pre-dose baseline Day 1 to Day 29
For the chronic study only, mood states (anxiety) questionnaire	Profile of Mood States (POMS) questionnaire, , 30 questions, How do you feel right now, rated 0 (not at all) to 4 (extremely)	Immediately prior to test of attention, change from pre-dose baseline Day 1 to Day 29
For the chronic study only, high frequency (HF) and low frequency (LF) domains of heart rate variability, a biomarker of cognitive function, during the tests of attention	Beats per minute via wearable heart rate monitor	Change from pre-dose baseline Day 1 to Day 29

Collaborators and Investigators

• Sponsor: PepsiCo Global R&D
• Investigators: Principal Investigator: Patrick J O'Connor, PhD, University of Georgia, Athens

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Actual): July 19, 2022
• Study Completion (Actual): July 19, 2022

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: cognition; attention; citicoline; attentional performance; CPT-III
• Other Study ID Numbers: PEP-2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No