Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04353076 |
| Other study ID # |
H 05-16-07 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2019 |
| Est. completion date |
April 2, 2021 |
Study information
| Verified date |
August 2021 |
| Source |
University of Ottawa |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Climate change not only affects the planet's natural resources, but also severely impacts
human health. An individual's ability to adequately cope with short- or long-term increases
in ambient temperature is critical for maintaining health and wellbeing. Prolonged increases
in temperature (heatwaves) pose a serious health risk for older adults, who have a reduced
capacity to efficiently regulate body temperature. However, information regarding the impact
of age on body temperature regulation during prolonged exposure to extreme heat is lacking,
as is research on the effectiveness of interventions aimed at reducing heat strain in such
situations. This project will address these important knowledge gaps by exposing healthy
young and older adults to a prolonged (9 hour) heat exposure, with conditions representative
of heatwaves in temperate continental climates. An additional cohort of older adults will
complete the same heatwave simulation but will be briefly (2 hours) exposed to cooler
conditions (22-23°C) mid-way through the session (akin to visiting a cooling centre or cooled
location). The investigators will evaluate age-related differences in the capacity to
dissipate heat via direct air calorimetry (a unique device that permits the precise
measurement of the heat dissipated by the human body) and their effect on the regulation of
body temperature. The investigators anticipate that older adults will exhibit progressive
increases in the heat stored in the body throughout the simulated heatwave, resulting in
progressive increases in body core temperature. Further, older adults exposed to brief-mid
day cooling will rapidly gain heat upon re-exposure to high ambient temperatures. As a
result, by the end of exposure body temperatures will be similar to the group not removed
from the heat.
Description:
OBJECTIVES Intervention 1: Evaluate the effect of age on whole-body heat storage, body core
temperature, and the development of cardiovascular strain and acute inflammation during
day-long (9 hours) exposure to simulated heatwave conditions.
Intervention 2: Determine whether short-duration exposure (2 hours) to an air-conditioned
environment following extreme heat exposure results in lasting reductions in physiological
strain in older adults upon return to the heat.
Hypotheses Intervention 1: Older adults will experience greater heat storage throughout the
9-hour simulated heatwave compared to the younger participants. Consequently, body core
temperature will be greater in the older adults and between-group differences will be
exacerbated as exposure progresses. We will also explore the secondary hypothesis that
differences in body temperature will be paralleled by greater alterations in cardiovascular
variables and acute circulatory and intracellular inflammation in the older adults.
Intervention 2: Body heat storage will be exacerbated in the older adults exposed to the
cooling centre intervention upon return to the heat (hours 5-6) compared to the older adults
from Intervention 1 who remained in the heat. Consequently, body core temperature will be
comparable (statistically equivalent) between groups by the end of exposure.
Methods Participants A total of 20 young (age: 18-31 years) and 40 older (age: 64-80 years)
adults will be recruited for the proposed project, with an approximately even distribution of
men and women in each intervention arm. Young (n = 20) and older (n = 20) adults will
complete Intervention 1 and a separate cohort of older adults (n = 20) will complete
Intervention 2. Participants will be homogenous for anthropomorphic characteristics as well
as habitual physical activity levels as verified via standardized questionnaires.
Experimental Design Pre-trial instructions All participants will be asked to avoid strenuous
physical activity and alcohol for 24 hours prior to all preliminary and experimental sessions
and to eat a light meal 2 hours before the start of each session. Participants will also be
asked to consume a minimum of 500 ml of water the night before and morning of each session to
ensure adequate hydration. Adequate hydration will be verified upon arrival to the laboratory
(urine specific gravity <1.025). For all sessions, participants will wear athletic shorts
(and a sport top for women).
Preliminary screening All participants will complete one preliminary evaluation a minimum of
7 days before the first experimental session. During this session they will be familiarized
with all procedures and measurement techniques and will complete the Get Active Questionnaire
(GAQ) and the American Heart Association Pre-participation screening Questionnaire to assess
their eligibility to participate. The GAQ will also be used to assess habitual activity
levels along with the Kohl Physical Activity Questionnaire. Participants will also provide
verbal and written informed consent at this time. Body height and mass will be determined via
a physician stadiometer and a high-performance weighing terminal, respectively, and from
these measurements body surface area will be calculated.
Experimental Protocol (Intervention 1) Each session will commence at 07:00-09:00. Upon
arrival to the laboratory, the participant will provide a urine sample for the assessment of
urine specific gravity, after which a measurement of nude body mass will be obtained.
Participants will then insert a temperature probe for the continuous measurement of rectal
temperature. Thereafter, participants will be instrumented for the measurement of skin
temperature and 5-lead echocardiogram. Baseline cardiovascular parameters will be evaluated
via a brief (~45 min) cardiovascular test battery, performed as follows. Brachial arterial
systolic and diastolic pressures reconstructed from arterial pressure waveforms measured at
the right middle finger (volume clamp technique) and 5-lead echocardiogram recordings will be
collected for 10-min while the participant rests quietly (spontaneous breathing). Immediately
thereafter, arterial systolic and diastolic pressures will be measured in triplicate via
manual auscultation (~30 sec between measures), after which forearm and calf blood flows on
the right side of the body will be measured via automated venous occlusion plethysmography.
Throughout the test battery, the participant will be seated with both feet on the floor,
except for during the measurements of limb blood flow, where the instrumented limbs will be
elevated to facilitate venous drainage. Finally, a venous blood sample and body mass
measurement will be obtained.
Participants will then be transferred to the whole-body direct calorimeter chamber, regulated
to 40°C and ~10-15% humidity. These conditions were chosen to simulate peak temperatures
experienced during heatwaves and are similar to peak conditions in recent heatwaves in North
America in 2018 (Ottawa, Ontario; 34°C and 58%, heat index: 41°C) and Europe in 2003 (Paris,
France; 38°C and 25%, heat index: 38°C). The participant will rest quietly for 3-hours (hours
1-3) within the calorimeter chamber while whole-body heat production and exchange are
measured continuously. At the 3-hour mark, the participant will exit the calorimeter and the
brief cardiovascular test battery will be performed again followed by a measurement of body
mass. Hours 4-6 will be spent resting in the heat in the thermal chamber adjacent to the
calorimeter. During this time, participants will be allowed to consume a light, self-provided
lunch with low water content. Tap water will be provided ad libitum via a self-service
insulated water cooler located in the thermal chamber. Another cardiovascular battery will
then be performed followed by a measurement of body mass. The participant will then re-enter
the calorimeter where the final 3 hours will be spent (hours 6-9). At the end of this period,
the participants will undergo a fourth and final cardiovascular test battery and a final
venous blood sample and body mass measurement will be procured.
Statistical analysis and sample size calculations Primary and secondary variables will be
evaluated using linear mixed-effects models. Time will be modelled as a repeated
within-subject fixed effect, and age-group will be modelled as a between-subject fixed
effect. Pre-heat exposure values of the outcome variable, participant sex, and self-reported
weekly physical activity (min/week, as assessed via the GAQ) will be included as covariates.
Participant identification will be modeled as a random effect in all analyses. Akaike's
information criterion will be used to determine random effect and variance/covariance
structures.
Post hoc multiple comparisons will be made on model estimated marginal means. Given the small
number of comparisons for each variable, multiplicity corrections will not be employed.
Homoscedasticity will be evaluated for all models by visual assessment of residual plots.
Approximate normal distribution of residuals will be assessed via visual inspection of
histograms and Q-Q plots. Data will be log-transformed in the event that the distribution of
residuals meaningfully deviates from normality. For all analyses, alpha will be set at 0.050.
Descriptive statistics will be presented as means and standard deviations. Comparisons
between groups and/or time-points will be presented as means and 95% confidence intervals
[lower limit, upper limit].
An a priori power analysis determined that a total sample size of 19 young and 19 older
adults was required to detect a difference in the rate of whole-body heat storage between
groups at the end of each calorimeter session (i.e., hours 3 and 9) with 80% statistical
power. In lieu of clinically meaningful data (i.e., what would be considered a clinically
meaningful change in whole-body heat storage), the standardized effect size (Cohen's d=1.06)
was calculated based on the difference in the rate of whole-body heat storage between young
and older adults over the final 30-min of a 3-hour heat exposure protocol (young: -2 [26]
kJ/hour, older: 43 [54] kJ/hour) in our previous work.
Experimental Protocol (Intervention 2) Experimental design The protocol for Intervention 2 is
identical to that of Intervention 1 except that after the first calorimeter session and
subsequent cardiovascular battery, participants will exit the thermal chamber and spend ~2
hours (hours 5-6) resting in an air-conditioned room (~23°C, ~50% relative humidity). Similar
to Intervention 1, participants will be allowed to eat a small self-provided lunch during
this time and consume water (tap) ad libitum. The third cardiovascular battery will also be
performed in the cooled environment. As in Intervention 1, participants will then re-enter
the calorimeter for the final 3 hours, where they will rest in the heat for the remainder of
the experimental session.
Statistical analysis and sample size calculations Statistical analysis for Intervention 2
will be performed to assess whether mid-day exposure to a cooled room results in greater body
heat storage following exposure such that physiological responses are similar to those of the
non-cooled group by the end of the 9-hour heatwave simulation. Cumulative whole-body heat
storage will be evaluated using a linear mixed-effects model with experimental group modelled
as a between-subject fixed effect. Cumulative heat storage over the first three hours of the
9-hour exposure will be included as a covariate to account for the influence of any inter- or
intra-individual factors (e.g., sex, physical activity levels), measured or unmeasured,
impacting whole-body heat exchange and storage. Comparisons of heat storage between groups
will be made using model estimated marginal means.
Body core temperature, as estimated by rectal temperature (primary outcome), will be analyzed
with a linear mixed effects model with experimental group (two levels: cooling and
no-cooling) modelled as a between-subject fixed effect and time as a repeated within-subject
fixed effect (0-, 1-, 2-, and 3-hours post-cooling intervention). Like the model for heat
storage, rectal temperature at the end of the first calorimetry session (i.e., hour 3 of the
9-hour exposure) will be included as a covariate to account for the influence of any measured
or unmeasured inter- or intra-individual factors impacting the body temperature responses to
resting heat exposure.
The effect of cooling on rectal temperature will then be assessed via two one-sided tests
performed on the mixed-effects model derived estimated marginal means at each timepoint.
Equivalence bounds will be set to ±0.3°C, which corresponds to the typical day-to-day
variation of core temperature and has been suggested to reflect a meaningful/detectable
change in body temperatures in a recent study assessing the influence of cooling strategies
on physiological strain in young adults. Secondary variables will be similarly evaluated. The
level of significance will be set at P < 0.050. Descriptive statistics will be presented as
mean (standard deviation) and comparisons between groups will be presented as mean ± 95%
confidence interval.
An a priori power analysis determined that a total sample size of 18 older adults in each
group (36 participants total) is required to confirm whether between-group differences in
rectal temperature are equivalent within upper and lower bounds of +0.3°C and -0.3°C,
respectively, with 80% power. This corresponds to an effect size (Cohen's d) of 1.0, based on
the pooled-standard deviation of 0.3°C, determined from published data from our laboratory
demonstrating a 0.2°C (SD 0.3) difference in core temperature between young and older adults
and a 0.0°C (SD 0.3) difference in core temperature between older adults with and without
type 2 diabetes following 3 hours of rest in a hot environment.
