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 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | 0454E |
| Sponsor | Ingenious Ingredients L.P. |
| Funder | Ingenious Ingredients, L.P. |
- 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
Plain English summary of protocol
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
Scientific
Texas A&M University
675 Kimbrough Blvd.
Building #1542
College Station, TX
77843-4253
United States of America
 ORCID ID |
0000-0002-3906-1658 |
|---|---|
| Phone | +1 (0)979 458 1498 |
| rbkreider@tamu.edu |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional double-blind randomized crossover controlled trial |
| Secondary study design | Randomised cross over trial |
| Study type | Participant information sheet |
| Scientific title | Effects of ParaXanthine supplementation with and without CAffeine on executive Function (PXCAF) |
| Study acronym | PXCAF |
| Study objectives | Paraxanthine, 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 |
| Health condition(s) or problem(s) studied | Executive functioning in healthy individuals |
| Intervention | Subjects 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 type | Supplement |
| Primary outcome measure(s) |
The 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: |
| Key secondary outcome measure(s) |
Safety measured using: |
| Completion date | 01/05/2021 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 13 |
| Total final enrolment | 13 |
| Key inclusion criteria | All 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 |
| Key exclusion criteria | Subjects 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 |
| Date of first enrolment | 01/01/2020 |
| Date of final enrolment | 28/02/2021 |
Locations
Countries of recruitment
- United States of America
Study participating centre
College Station
77843-4253
United States of America
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request, Published as a supplement to the results publication |
| IPD sharing plan | All 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 | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
17/05/2024: Publication reference added.
04/01/2022: Trial's existence confirmed by Texas A&M University.
