Mirabegron and Physiological Function in Cold Environments

• Status: Not yet recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Indiana University
• Collaborator: Office of Naval Research (ONR)
• Treatments: Mirabegron

Criteria

Inclusion Criteria:

• Men and women

• 18-40 years old

• Participate in 150 minutes or more of at least moderate intensity exercise per week during the previous 2 years

Exclusion Criteria:

• diagnosed autonomic disease

• diagnosed cardiovascular disease

• diagnosed metabolic disease

• diagnosed neurologic disease

• diagnosed endocrine disease

• diagnosed respiratory disease

• diagnosed liver dysfunction

• diagnosed kidney dysfunction

• Women who are pregnant or breastfeeding

• Individuals currently taking a medication (with the exception of birth control, including hormonal contraception) that cannot be safely discontinued for 5 biological half-lifes prior to each study visit based on consultation with the study physician.

• Current tobacco or electronic cigarette use or consistent use within the last 1 year