Mirabegron and Physiological Function in Cold Environments
Status:
Not yet recruiting
Trial end date:
2023-05-01
Target enrollment:
Participant gender:
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 addressing these specific aims: 1) determine which dose of mirabegron administration
will increase thermogenesis during 6 hours of a mild cold stress challenge, 2) determine if
acute mirabegron administration will delay the fall in core temperature and the onset of
shivering during a progressive cold-water immersion challenge, and 3) compare the dose of
isoproterenol required to evoke a thermogenic response equal to a 15% increase above rest,
following ingestion of either mirabegron or a placebo. In addition to filling these knowledge
gaps, the activation of brown adipose tissue by mirabegron might be influenced by the gut
microbiome. Therefore, the association between the gut microbiome and mirabegron metabolism
will be explored. Collectively, these studies 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.