Mirabegron and Physiological Function in Cold Environments

Sponsor

Indiana University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04766021

Collaborator

Office of Naval Research (ONR) (U.S. Fed)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Resting Energy Expenditure Thermogenesis Brown Adipose Tissue	Drug: Mirabegron	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Mirabegron and Physiological Function in Cold Environments

Anticipated Study Start Date :

May 1, 2021

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room	Drug: Mirabegron Dose-response effect on thermogenesis
Experimental: 100 mg Mirabegron Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room	Drug: Mirabegron Dose-response effect on thermogenesis
Experimental: 150 mg Mirabegron Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room	Drug: Mirabegron Dose-response effect on thermogenesis
Experimental: 200 mg Mirabegron Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room	Drug: Mirabegron Dose-response effect on thermogenesis

Outcome Measures

Primary Outcome Measures

Resting Energy Expenditure [Baseline]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [30 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [60 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [90 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [120 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [150 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [180 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [210 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [240 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [270 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [300 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [330 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry
Resting Energy Expenditure [360 minutes]
Resting energy expenditure will be measured via whole body indirect calorimetry

Secondary Outcome Measures

Core Body Temperature [Baseline]
Core Body temperature will be measured via rectal temperature
Core Body Temperature [1 hour]
Core Body temperature will be measured via rectal temperature
Core Body Temperature [2 hour]
Core Body temperature will be measured via rectal temperature
Core Body Temperature [3 hour]
Core Body temperature will be measured via rectal temperature
Core Body Temperature [4 hour]
Core Body temperature will be measured via rectal temperature
Core Body Temperature [5 hour]
Core Body temperature will be measured via rectal temperature
Core Body Temperature [6 hour]
Core Body temperature will be measured via rectal temperature
Brown adipose tissue activation [Baseline]
Infrared thermography will be used to measure supraclavicular skin temperature as an estimate of brown adipose tissue activation
Brown adipose tissue activation [1 hour]
Infrared thermography will be used to measure supraclavicular skin temperature as an estimate of brown adipose tissue activation
Brown adipose tissue activation [2 hour]
Infrared thermography will be used to measure supraclavicular skin temperature as an estimate of brown adipose tissue activation
Brown adipose tissue activation [3 hour]
Infrared thermography will be used to measure supraclavicular skin temperature as an estimate of brown adipose tissue activation
Brown adipose tissue activation [4 hour]
Infrared thermography will be used to measure supraclavicular skin temperature as an estimate of brown adipose tissue activation
Brown adipose tissue activation [5 hour]
Infrared thermography will be used to measure supraclavicular skin temperature as an estimate of brown adipose tissue activation
Brown adipose tissue activation [6 hour]
Infrared thermography will be used to measure supraclavicular skin temperature as an estimate of brown adipose tissue activation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Indiana University
Office of Naval Research (ONR)

Investigators

Principal Investigator: Blair D Johnson, PhD, Indiana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Blair D. Johnson, Associate Professor School of Public Health, Indiana University

ClinicalTrials.gov Identifier:

NCT04766021

Other Study ID Numbers:

2011690870

First Posted:

Feb 23, 2021

Last Update Posted:

Feb 23, 2021

Last Verified:

Feb 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Mirabegron

Study Results

No Results Posted as of Feb 23, 2021