Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT05990387 |
Other study ID # |
2011690870; Aim 2 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 1/Phase 2
|
First received |
|
Last updated |
|
Start date |
July 19, 2023 |
Est. completion date |
April 23, 2024 |
Study information
Verified date |
April 2024 |
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 if acute mirabegron administration will delay the fall in core
temperature and the onset of shivering during a progressive cold-water immersion 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 3 visits to the laboratory; one informed
consent/screening visit and 2 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 ingest either a placebo or one dose of
mirabegron prior to entering our water immersion tank. Then they will be instrumented for the
measurement of heart rate (3-lead ECG), blood pressure (brachial artery auscultation), core
temperature (rectal thermistor), and indices of shivering (surface mechanomyography using
triaxial accelerometers at 3 anatomic sites (chest, upper back, and thigh), oxygen
consumption via ventilation and expired gases, and the bedside shivering assessment scale).
Thermal perceptions will be assessed using Likert scales for thermal discomfort and thermal
sensation. Following 10 minutes of resting baseline measurements, infrared thermography will
then be used to measure skin temperature of the supraclavicular fossa as an estimate of brown
adipose tissue activation and thermal perceptions will be assessed.
The measurement of supraclavicular fossa skin temperature (infrared thermography) and thermal
perceptions will be assessed every 10 minutes prior to the progressive cold-water challenge.
After 30 minutes of seated rest, pre-immersion measurements of heart rate, blood pressure,
core temperature, shivering, and thermal perceptions will be conducted and an infrared
thermography image will be taken. Then, the water immersion tank will be filled up to the
participant's neck with 35 degrees C (95 degrees F) water. Heart rate, blood pressure, core
temperature, and shivering indices will be continuously measured. Infrared thermography and
thermal perceptions will be obtained every 5 minutes throughout the progressive cold-water
challenge. The temperature of the water will be progressively lowered by ~12 degrees C every
60 minutes until the water temperature reaches 10 degrees C (50 degrees F) or until the
participant can no longer tolerate the cold or if rectal temperature reaches 35.5 degrees C
(95.9 degrees F). Upon completion of the progressive cold water challenge, the water in the
tank will be rapidly emptied. Participants will gently towel dry and will be able to don a
circulating warm water perfused suit and/or use a mylar blanket to reestablish core
temperature.
Participants will be asked to return to the laboratory after 10-14 days to repeat the
experiment with the drug assignment not yet received. Each participant's order of assignment
to placebo or drug ingestion (prior to the cold water challenge) over the 2 study visits will
be randomly assigned.