A Phase 1/2 interventional study of Mirabegron and Placebo in Resting Energy Expenditure, Thermogenesis and Brown Adipose Tissue, sponsored by Indiana University. Completed at 1 site in United States. Open to participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-07-03.
Sponsored by Indiana University · Phase 1/2, Interventional, and Basic science
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 determining if acute mirabegron administration will delay the fall in core temperature and the onset of shivering during a progressive cold-water immersion challenge. This study is part of a collection of studies that 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.
This is a randomized, double-blind, placebo-controlled, cross-over experimental design. Participants will be asked to complete 3 visits to the laboratory; one informed consent/screening visit and 2 study visits. On study visit days, participants will report to the laboratory following a 12-hour fast, and 24-hour abstention from exercise, caffeine, and alcohol. During the study visits, participants will ingest either a placebo or one dose of mirabegron prior to entering our water immersion tank. Then they will be instrumented for the measurement of heart rate (3-lead ECG), blood pressure (brachial artery auscultation), core temperature (rectal thermistor), and indices of shivering (surface mechanomyography using triaxial accelerometers at 3 anatomic sites (chest, upper back, and thigh), oxygen consumption via ventilation and expired gases, and the bedside shivering assessment scale). Thermal perceptions will be assessed using Likert scales for thermal discomfort and thermal sensation. Following 10 minutes of resting baseline measurements, infrared thermography will then be used to measure skin temperature of the supraclavicular fossa as an estimate of brown adipose tissue activation and thermal perceptions will be assessed.
The measurement of supraclavicular fossa skin temperature (infrared thermography) and thermal perceptions will be assessed every 10 minutes prior to the progressive cold-water challenge. After 30 minutes of seated rest, pre-immersion measurements of heart rate, blood pressure, core temperature, shivering, and thermal perceptions will be conducted and an infrared thermography image will be taken. Then, the water immersion tank will be filled up to the participant's neck with 35 degrees C (95 degrees F) water. Heart rate, blood pressure, core temperature, and shivering indices will be continuously measured. Infrared thermography and thermal perceptions will be obtained every 5 minutes throughout the progressive cold-water challenge. The temperature of the water will be progressively lowered by \~12 degrees C every 60 minutes until the water temperature reaches 10 degrees C (50 degrees F) or until the participant can no longer tolerate the cold or if rectal temperature reaches 35.5 degrees C (95.9 degrees F). Upon completion of the progressive cold water challenge, the water in the tank will be rapidly emptied. Participants will gently towel dry and will be able to don a circulating warm water perfused suit and/or use a mylar blanket to reestablish core temperature.
Participants will be asked to return to the laboratory after 10-14 days to repeat the experiment with the drug assignment not yet received. Each participant's order of assignment to placebo or drug ingestion (prior to the cold water challenge) over the 2 study visits will be randomly assigned.
Indiana University is the lead sponsor of 958 studies on the registry; 200 are open to participants now.
Of its 142 completed or terminated interventional studies of FDA-regulated products, 112 (79%) have results posted.
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Exclusion Criteria:
Given once, followed by observation for up to 4 hours in a progressively cold water challenge
Drug: Placebo
Given once, followed by observation for up to 4 hours in a progressively cold water challenge
Drug: Mirabegron
Dose-response effect on thermogenesis
Also known as: Myrbetriq
Placebo control condition
Cold Temperature Deflection Point
Core temperature will be continuously measured using rectal thermistors. The point at which core temperature begins to fall (i.e., deflection point) will be identified using Prism 8 software by plotting core temperature vs. water temperature.
Time frame: Through session completion, up to 4 hours
Thermogenesis - Oxygen Consumption
Oxygen consumption is one measure of shivering. A pneumotach connected to a mouthpiece or facemask will be used to measure the flow of inspired and expired air. Expired gases will be sampled using oxygen and carbon dioxide sensors to determine oxygen consumption and carbon dioxide production.
Time frame: Through session completion, up to 4 hours
Shivering Inflection Point - Surface Mechanomyography
Surface Mechanomyography is one measure of shivering. Three triaxial accelerometers adhered to the skin using adhesive tape on the chest, upper back, and thigh were used to assess shivering. The inflection point was determined using segmental analysis for each person to identify when an abrupt increase in shivering occurred.
Time frame: Through session completion, up to 4 hours
Shivering Inflection Point - Bedside Shivering Scale
The Bedside Shivering Scale is one measure of shivering. Two investigators will subjectively assess shivering by the participants using a Likert scale (0 = none, 3 = Severe) and the scores will be averaged. The inflection point was determined using segmental analysis for each person to identify when an abrupt increase in the bedside shivering scale occurred.
Time frame: Through session completion, up to 4 hours
| Milestone | Placebo First, Then Mirabegron | Mirabegron First, Then Placebo |
|---|---|---|
| Started | 8 | 9 |
| Completed | 5 | 7 |
| Not completed | 3 | 2 |
| Withdrew: Withdrawal by subject | 3 | 2 |
| Milestone | Placebo First, Then Mirabegron | Mirabegron First, Then Placebo |
|---|---|---|
| Started | 5 | 7 |
| Completed | 5 | 7 |
| Not completed | 0 | 0 |
Core temperature will be continuously measured using rectal thermistors. The point at which core temperature begins to fall (i.e., deflection point) will be identified using Prism 8 software by plotting core temperature vs. water temperature.
| degrees Celsius | Placebo | 100 mg Mirabegron |
|---|---|---|
| Cold Temperature Deflection Point | 22.8 ± 5.67 | 22.97 ± 7.42 |
Oxygen consumption is one measure of shivering. A pneumotach connected to a mouthpiece or facemask will be used to measure the flow of inspired and expired air. Expired gases will be sampled using oxygen and carbon dioxide sensors to determine oxygen consumption and carbon dioxide production.
| ml of oxygen / min / kg of body mass | Placebo | 100 mg Mirabegron |
|---|---|---|
| Thermogenesis - Oxygen Consumption | 7.2 ± 3.1 | 7.6 ± 3.3 |
Surface Mechanomyography is one measure of shivering. Three triaxial accelerometers adhered to the skin using adhesive tape on the chest, upper back, and thigh were used to assess shivering. The inflection point was determined using segmental analysis for each person to identify when an abrupt increase in shivering occurred.
| degrees Celsius | Placebo | 100 mg Mirabegron |
|---|---|---|
| Shivering Inflection Point - Surface Mechanomyography | 24.1 ± 2.8 | 22.7 ± 3.6 |
The Bedside Shivering Scale is one measure of shivering. Two investigators will subjectively assess shivering by the participants using a Likert scale (0 = none, 3 = Severe) and the scores will be averaged. The inflection point was determined using segmental analysis for each person to identify when an abrupt increase in the bedside shivering scale occurred.
| degrees celsius | Placebo | 100 mg Mirabegron |
|---|---|---|
| Shivering Inflection Point - Bedside Shivering Scale | 22.1 ± 2.5 | 19.8 ± 3.9 |
Collected over Adverse event data were collected for each subject after informed consent was obtained and up to their study completion (up to 6 months).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| 100 mg Mirabegron | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| Age, Categorical(Participants) | All Participants |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 12 |
| >=65 years | 0 |
| Age, Continuous(years) | All Participants |
|---|---|
| Mean | 25 ± 6 |
| Sex: Female, Male(Participants) | All Participants |
|---|---|
| Female | 6 |
| Male | 6 |
| Race and Ethnicity Not Collected(Participants) | All Participants |
|---|
| Region of Enrollment(participants) | All Participants |
|---|---|
| United States | 12 |
| Body Mass Index(kg/m^2) | All Participants |
|---|---|
| Mean | 26 ± 5 |
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Indiana University