Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05806476 |
| Other study ID # |
SMU_ETHICS_2021-22-319 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 22, 2023 |
| Est. completion date |
May 30, 2023 |
Study information
| Verified date |
March 2023 |
| Source |
St. Mary's University, Twickenham |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
A study investigating the effects of acute caffeine intake on cognition based on genes
associated with caffeine metabolism and physiological effect.
Description:
A double-blind, placebo-controlled crossover design that incorporates alternating periods of
'long-term' caffeine exposure and abstinence will be employed to investigate the
inter-individual effects of caffeine on cognitive performance. The procedure that
participants need to follow on each of the four weeks of the study is described in detail
below.
1. Baseline visit: baseline questionnaire, anthropometry, familiarisation with study
procedures and tasks. Participants will be supplied with week 1 supplementation (n= 18
capsules) and saliva vials (n= 6) for saliva sample collection. Participants will also
be provided with decaffeinated coffee, tea and cocoa, depending on their preferences.
2. Days 1-6: placebo or caffeine capsules x 3 per day at 09.00, 11.00, and 15.00.
Compliance with the caffeine and placebo supplementation will be assessed by a saliva
sample at 17.00 every day for each of the days on long-term supplementation. Caffeine
concentrations in blood and saliva correlate highly, and levels typically increase
progressively during the day (due to intermittent consumption of caffeine beverages).
The best single-sample bioassay of daily caffeine intake is provided by samples obtained
in the late afternoon (James, 1994; James & Rogers, 2005).
3. Days 5 and 6: In preparation for the 'challenge' days and to control for environmental
factors which have been shown to affect inducibility of CYP1A2 enzyme, participants will
be asked to abstain from alcohol for 48 h and avoid strenuous exercise for 24 h before
the trials and avoid consumption of cruciferous foods (broccoli and Brussels sprouts)
(Gunes & Dahl, 2008). Finally, participants will be provided with diet diaries to record
all food and beverages consumed during the 24 h before all four experimental trials.
4. Day 7 (Experimental day): Participants will be asked to present to the laboratory after
an overnight fast and they will follow the procedure shown below:
09:00: Pre-supplementation saliva sample & cognitive tasks
09:30: Supplementation with 3 mg / kg body mass caffeine or placebo
10:30: First post-supplementation saliva sample & cognitive tasks
12:30: Second post-supplementation saliva sample & cognitive tasks
13:00: A meal containing of fruit juice or soft drink and a cheese sandwich
15:30: Third post-supplementation saliva sample & cognitive tasks
Saliva samples will be taken upon arrival and 1, 3 and 6 h post-supplementation. The first
sample will be taken to verify adherence to the requirement not to take their morning
supplementation, thus be in caffeine abstinence, regardless of the study arm. It has been
shown that 1 mg/kg of caffeine results in caffeine plasma levels of about 1 μg/ml and
salivary caffeine concentration may be expected to be about 70% of plasma levels (Walther et
al., 1983). Mean saliva caffeine levels below 1 μg / ml have been previously reported for
overnight caffeine abstinence (Evans & Griffiths, 1999). Following caffeinated treatment,
salivary caffeine levels will aid in determination of caffeine metabolism (Dodd et al.,
2015).
The supplementation will be swallowed with water proportional to participant weight (3-ml/kg
body mass). During the experimental days, participants will be asked to consume water ad
libitum in their first trial and an equal volume in the subsequent trials. They will also be
asked to avoid exercise between the trials.
The cognitive tasks will be performed on four time points: pre- and 1, 3 and 6 h
post-supplementation. When using anhydrous caffeine in capsules, peak caffeine concentration
usually occurs around 1 h post ingestion (Graham, 2001). Therefore, measuring caffeine
metabolites for 1 h post-caffeine ingestion would mostly measure caffeine absorption and not
metabolism, which is determined by CYP1A2 enzyme. Thus, studies investigating the effects of
CYP1A2 genotypes on caffeine effects should focus on using protocols which last >1 h, since
these effects may be more evident in events lasting longer than 1 h, where the metabolism of
caffeine may have a more pronounced effect. It should also be noted that the half-life of
caffeine is on average 4-6 h (Nehlig, 2018) in most adults and it is not yet known to what
degree caffeine metabolism is altered between fast and slow metabolisers. Therefore, it is
unknown at what time point there would be a large enough difference in the circulating levels
of caffeine between fast and slow metabolisers to have a significant impact on the
ergogenicity of caffeine (Southward et al., 2018). For this reason, we selected 3 different
time points post-supplementation to complete the cognitive tasks: 1 h post-supplementation
was selected to permit comparison with several previous caffeine studies, because it is the
most frequently used time point to test cognitive performance post-supplementation in the
literature (Carswell et al., 2020). We also added the 3 h and 6 h post-supplementation time
points since they are within the average range of caffeine half-life and to investigate the
differences in performance between 'fast' and 'slow' metabolisers. We hypothesise that those
who metabolise caffeine faster would not maintain high saliva levels of caffeine throughout
the 6 h event compared to those with a slower metabolism of caffeine.
At the end of each experimental day, participants will be supplied with the capsules for the
following week, as well as the vials for saliva caffeine sampling.
Once provided, samples will be kept frozen at -20 °C until analysis. Salivary caffeine levels
will be measured using the Enzyme Multiplied Immunoassay Technique (EMIT) by
spectrophotometric method. The EMIT assay is a homogenous enzyme immunoassay intended for use
in determining caffeine as a metabolite and will be preferred given that it is less invasive
than using serum caffeine and has been shown reliable and reproducible (Tripathi et al.,
2015). Serum caffeine levels greater than 30 μg / ml require dilution when analysed by EMIT
assay.
