Does paraxanthine provide greater improvement in cognitive function than caffeine or in combination with caffeine prior to and following running?

ISRCTN ISRCTN14506218
DOI https://doi.org/10.1186/ISRCTN14506218
Secondary identifying numbers 0454E
Submission date
01/01/2022
Registration date
04/01/2022
Last edited
17/05/2024
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Other
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English Summary

Background and study arms
Paraxanthine (PX) is a natural dietary component that can be found in different parts of Theobroma cacao (cocoa tree) fruits, in Coffea arabica (coffee plant), in Sinomenium actum (a traditional Chinese herbal medicine), and in citrus flowers. PX is the major metabolite (breakdown product) of caffeine (CA) in humans and is less toxic than caffeine. One-time ingestion of as little as 50 mg PX has been shown to improve cognition, short-term memory and helps to sustain attention. However, if paraxanthine is more effective than CA, or has synergistic effects when combined with CA, is currently unknown. The aim of this study is to measure the effects of paraxanthine with and without caffeine and compared to CA on brain function.

Who can participate?
Healthy males and females between the ages of 18 to 40 years

What does the study involve?
Participants will perform two cognitive function tests that assess a range of cognitive and executive function aspects. Then participants will be randomly allocated to receive PX, CA, PX+CA or placebo (dummy) capsules, and then perform the same cognitive function tests. Following a 10-kilometer run, participants will perform the same cognitive function tests a third time.

What are the possible benefits and risks of participating?
The potential benefit of participating is an increase in executive functioning. Paraxanthine is self-affirmed GRAS (generally recognized as safe) and studies have shown PX is less toxic than CA.

Where is the study run from?
Texas A&M University (USA)

When is the study starting and how long is it expected to run for?
July 2019 to May 2021

Who is funding the study?
Ingenious Ingredients L.P. (USA)

Who is the main contact?
Richard B. Kreider
rbkreider@tamu.edu

Contact information

Prof Richard Kreider
Scientific

Texas A&M University
675 Kimbrough Blvd.
Building #1542
College Station, TX
77843-4253
United States of America

ORCiD logoORCID ID 0000-0002-3906-1658
Phone +1 (0)979 458 1498
Email rbkreider@tamu.edu

Study information

Study designInterventional double-blind randomized crossover controlled trial
Primary study designInterventional
Secondary study designRandomised cross over trial
Study setting(s)Other
Study typeOther
Participant information sheet No participant information sheet available
Scientific titleEffects of ParaXanthine supplementation with and without CAffeine on executive Function (PXCAF)
Study acronymPXCAF
Study hypothesisParaxanthine, the main metabolite of caffeine in humans, is an effective nootropic agent at doses as low as 50 mg. However, if paraxanthine shows greater beneficial effects on cognition compared to caffeine, or synergistic effects when combined with caffeine is currently unknown.
Ethics approval(s)Approved 04/12/2019, Texas A&M University Institutional Review Board (517 Blocker Building, 155 Ireland Street, Texas A&M University, College Station, TX 778431, USA; +1 (0)979 458 4067; irb@tamu.edu), ref: IRB2019-0928
ConditionExecutive functioning in healthy individuals
InterventionSubjects consume capsules containing 400 mg of placebo (PL); or 200 mg of PL + 200 mg of caffeine (CA); or 200 mg of PL+ 200 mg of PX (ENFINITY™, Ingenious Ingredients, Lewisville, TX, USA); or 200 mg CA + 200 mg of PX (CA+PX) with a 7 – 14 day washout between treatments. Capsules are taken with 8 ounces of water. A computer-generated randomization to treatment is used. Once subjects are randomized to start, they follow the counterbalance progression.

Procedure for each treatment period:
Upon arriving at the lab, participants had weight, resting heart rate, and blood pressure determined. Participants then completed a side effects questionnaire, performed cognitive function tests, donated a fasting blood sample, and then ingested 1 of 4 randomly assigned oral supplements (PRE). Participants then rested for 15-minutes and repeated these tests. Volunteers then performed a 10-km run time-trial at their self-determined pace.
Intervention typeSupplement
Primary outcome measureThe Psychology Experiment Building Language (PEBL) software program (Version 2.1, http://pebl.sourceforge.net) was used to administer four cognitive function tests that assessed a range of cognitive and executive function aspects:
1. Berg-Wisconsin Card Sorting Task test (BCST) at baseline, 1 hour after initial ingestion and after the completion of a 10-kilometer run.
2. Psychomotor Vigilance Task Test (PVTT) at baseline, 1 hour after initial ingestion and after the completion of a 10-kilometer run.
Secondary outcome measuresSafety measured using:
1. Side Effect Questionnaire at baseline, 1 hour after initial ingestion and after the completion of a 10-kilometer run.
2. Changes in blood clinical chemistries at baseline, 1 hour after initial ingestion and after the completion of a 10-kilometer run.
3. Changes in heart rate after initial ingestion and after each kilometer runing.
Overall study start date01/07/2019
Overall study end date01/05/2021

Eligibility

Participant type(s)Healthy volunteer
Age groupAdult
SexBoth
Target number of participants13
Total final enrolment13
Participant inclusion criteriaAll subjects were healthy and free from known: (1) a medical condition which hinders performance in a standard exercise program; (2) a history of cognitive dysfunction; (3) been currently taking prescription medications; (4) a known allergy to wheat flour; (5) a sleep disorder; (6) been/were pregnant or breastfeeding; or (7) a physician’s order to abstain/restrict caffeine or stimulant intake
Participant exclusion criteriaSubjects who were taking prescription medications in the month prior to the initiation of the study and/or were told by a physician to abstain or restrict physical exercise, caffeine and/or stimulant intake
Recruitment start date01/01/2020
Recruitment end date28/02/2021

Locations

Countries of recruitment

  • United States of America

Study participating centre

Texas A&M University
675 Kimbrough Blvd. Building #1542
College Station
77843-4253
United States of America

Sponsor information

Ingenious Ingredients L.P.
Industry

2560 King Arthur Blvd. Suite 124-74
Lewisville, TX
75056
United States of America

Phone +1 704 619 1692
Email info@ingeniousingredients.com
Website http://www.ing2.com

Funders

Funder type

Industry

Ingenious Ingredients, L.P.

No information available

Results and Publications

Intention to publish date30/06/2022
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request, Published as a supplement to the results publication
Publication and dissemination planPlanned publication in a peer-reviewed scientific journal.
IPD sharing planAll data generated or analysed during this study will be included in the subsequent results publication. Please contact Prof. Dr Richard Kreider (rbkreider@tamu.edu) with any requests.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article 09/05/2024 17/05/2024 Yes No

Editorial Notes

17/05/2024: Publication reference added.
04/01/2022: Trial's existence confirmed by Texas A&M University.