Mirabegron and Physiological Function in Cold Environments
Mirabegron and Physiological Function in Cold Environments
| Sponsors |
Lead Sponsor: Indiana University Collaborator: Office of Naval Research (ONR) |
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| Source | Indiana University | ||||||||||||||||||||||||||||||
| Brief 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. |
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| Overall Status | Not yet recruiting | ||||||||||||||||||||||||||||||
| Start Date | May 2021 | ||||||||||||||||||||||||||||||
| Completion Date | May 2023 | ||||||||||||||||||||||||||||||
| Primary Completion Date | May 2023 | ||||||||||||||||||||||||||||||
| Phase | Phase 1/Phase 2 | ||||||||||||||||||||||||||||||
| Study Type | Interventional | ||||||||||||||||||||||||||||||
| Primary Outcome |
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| Secondary Outcome |
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| Enrollment | 30 | ||||||||||||||||||||||||||||||
| Condition | |||||||||||||||||||||||||||||||
| Intervention |
Intervention Type: Drug Intervention Name: Mirabegron Description: Dose-response effect on thermogenesis |
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| Eligibility |
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 Gender: All Minimum Age: 18 Years Maximum Age: 40 Years Healthy Volunteers: Accepts Healthy Volunteers |
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| Overall Official |
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| Overall Contact |
Last Name: Blair D Johnson, PhD Phone: 8128558699 Email: [email protected] |
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| Verification Date |
February 2021 |
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| Responsible Party |
Type: Principal Investigator Investigator Affiliation: Indiana University Investigator Full Name: Blair D. Johnson Investigator Title: Associate Professor School of Public Health |
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| Has Expanded Access | No | ||||||||||||||||||||||||||||||
| Number Of Arms | 4 | ||||||||||||||||||||||||||||||
| Arm Group |
Label: Placebo Type: Placebo Comparator Description: Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room Label: 100 mg Mirabegron Type: Experimental Description: Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room Label: 150 mg Mirabegron Type: Experimental Description: Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room Label: 200 mg Mirabegron Type: Experimental Description: Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room |
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| Patient Data | No | ||||||||||||||||||||||||||||||
| Study Design Info |
Allocation: Randomized Intervention Model: Crossover Assignment Primary Purpose: Basic Science Masking: Double (Participant, Investigator) |
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