Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04766021 |
| Other study ID # |
2011690870; Aim 1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
November 30, 2021 |
| Est. completion date |
April 27, 2023 |
Study information
| Verified date |
July 2023 |
| Source |
Indiana University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Many Navy diving operations are performed in cold water. Despite technical advances to
improve thermal protection for cold water diving, these applications are cumbersome and do
not provide complete thermal protection as thermal discomfort is subjectively reported by
many Navy divers. Brown adipose tissue is highly thermogenic in humans. Therefore, activation
of brown adipose tissue might improve cold water tolerance and lower thermal discomfort
during cold water diving operations. Mirabegron is a beta-3-adrenergic receptor agonist that
is used to treat overactive bladder. Beta-3-adrenergic receptors are located on the urinary
bladder, gallbladder and brown adipose tissue. Recent evidence has demonstrated that acute
mirabegron administration increases thermogenesis for ~3 hours in humans. However, it is
currently not known which dose of mirabegron can increase thermogenesis for longer durations.
It is also not known if mirabegron administration can improve cold water tolerance and
thermal discomfort during cold water immersion. Finally, it is not known if mirabegron can
increase thermogenesis during sympathetic stimulation. This project will fill these knowledge
gaps by determining which dose of mirabegron administration will increase thermogenesis
during 6 hours of a mild cold stress challenge. This study is part of a collection of studies
that will show if mirabegron is a potential ergogenic aid that can be used to improve cold
water tolerance in Navy divers which will ultimately improve the likelihood of successful
missions.
Description:
This is a randomized, double-blind, placebo-controlled, cross-over experimental design.
Participants will be asked to complete 5 visits to the laboratory; one informed
consent/screening visit and 4 study visits. On study visit days, participants will report to
the laboratory following a 12-hour fast, and 24-hour abstention from exercise, caffeine, and
alcohol. During the study visits, participants will be instrumented for skin temperature
(12-sites: calf, shin, front of the thigh, back of the thigh, chest, upper back, forehead,
lower back, abdomen, forearm, hand, and foot; iButtons) core temperature (rectal thermistor),
indices of shivering (surface mechanomyography using triaxial accelerometers at 3 anatomic
sites (chest, upper back, and thigh) and the bedside shivering assessment scale), brachial
artery blood pressure (brachial artery auscultation), and heart rate (3-lead ECG). Thermal
perceptions will be assessed using Likert scales for thermal discomfort and thermal
sensation. Participants will be shirtless (sports bra for women) and will wear shorts
throughout the study. After 20 minutes of quiet resting in the supine position, 5 minutes of
baseline measurements will be taken, thermal perceptions and an infrared thermography image
of the supraclavicular fossa will be obtained as an indicator of brown adipose tissue
activation (6), and a whole blood sample will be obtained.
Participants will then ingest mirabegron (100 mg, 150 mg, or 200 mg) or placebo. Thirty
minutes after mirabegron or placebo has been ingested, participants will enter the whole-body
indirect calorimeter; the internal temperature of the calorimeter will be set to 20 degrees C
(68 degrees F). This will elicit a mild cold stress over the 6 hours of observation in the
whole-body indirect calorimeter. The whole-body indirect calorimeter provides an accurate and
continuous measure of thermogenesis (in the form of energy expenditure) that can be used over
long periods of time in a stable environment. The whole-body calorimeter is designed to
perform human studies that are up to 48 hours in duration and contains a private washroom.
While in the whole-body indirect calorimeter, participants will be instructed to be sedentary
and will be allowed to watch television or read. In order to stay consistent between study
visits, participants will be instructed to spend the same amount of time watching television
or reading for each study visit. Every 30 minutes, we will record skin temperatures, core
temperature, blood pressure, and heart rate. Thermogenesis will be determined by having
participants lie supine for 30 minutes and resting energy expenditure will be calculated
using the abbreviated Weir formula every hour (5). Thermal perceptions and an infrared
thermography image will also be obtained at these time points. At approximately the midpoint
of the 6-hour measurement period, participants will have the opportunity to use the restroom
and an additional urine sample will be collected at this time. At the end of the 6-hour
measurement period, participants will exit the whole-body indirect calorimeter and final
measurements of skin temperature, core temperature, heart rate, and blood pressure will be
obtained as well as a final infrared thermography image and a whole blood sample. After the
experiment is complete, participants will be given a mylar blanket to re-warm themselves
prior to leaving the laboratory.
Participants will be asked to return to the laboratory after 10-14 days to repeat the
experiment until all 4 dosing conditions (placebo, 100 mg, 150 mg, and 200 mg of mirabegron)
have been tested. Each participant's order of assignment to placebo or drug dosing over the 4
study visits will be randomly assigned.
