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)

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.

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
Measure Time Frame
Resting Energy Expenditure Baseline
Resting Energy Expenditure 30 minutes
Resting Energy Expenditure 60 minutes
Resting Energy Expenditure 90 minutes
Resting Energy Expenditure 120 minutes
Resting Energy Expenditure 150 minutes
Resting Energy Expenditure 180 minutes
Resting Energy Expenditure 210 minutes
Resting Energy Expenditure 240 minutes
Resting Energy Expenditure 270 minutes
Resting Energy Expenditure 300 minutes
Resting Energy Expenditure 330 minutes
Resting Energy Expenditure 360 minutes
Secondary Outcome
Measure Time Frame
Core Body Temperature Baseline
Core Body Temperature 1 hour
Core Body Temperature 2 hour
Core Body Temperature 3 hour
Core Body Temperature 4 hour
Core Body Temperature 5 hour
Core Body Temperature 6 hour
Brown adipose tissue activation Baseline
Brown adipose tissue activation 1 hour
Brown adipose tissue activation 2 hour
Brown adipose tissue activation 3 hour
Brown adipose tissue activation 4 hour
Brown adipose tissue activation 5 hour
Brown adipose tissue activation 6 hour
Enrollment 30
Condition
Intervention

Intervention Type: Drug

Intervention Name: Mirabegron

Description: Dose-response effect on thermogenesis

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

Overall Official
Last Name Role Affiliation
Blair D Johnson, PhD Principal Investigator Indiana University
Overall Contact

Last Name: Blair D Johnson, PhD

Phone: 8128558699

Email: [email protected]

Verification Date

February 2021

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Indiana University

Investigator Full Name: Blair D. Johnson

Investigator Title: Associate Professor School of Public Health

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

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Basic Science

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov