Resting Energy ExpenditurePhase 1/2NCT05990387
MIrabegron and Physiological Function in Cold Environments
A Phase 1/2 study testing Mirabegron in people with Resting Energy Expenditure and Thermogenesis, run by Indiana University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Resting Energy Expenditure, Thermogenesis, Brown Adipose Tissue
- What is being tested?
- Mirabegron
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jul 2023to 23 Apr 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- diagnosed autonomic disease
- diagnosed cardiovascular disease
- diagnosed metabolic disease
- diagnosed neurologic disease
- diagnosed endocrine disease
- diagnosed respiratory disease
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mirabegron and Physiological Function in Cold Environments - Aim 1
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.
Read the detailed description
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.
- Being tested
- Mirabegron, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirabegronDrug
Also called Myrbetriq
Dose-response effect on thermogenesis
PlaceboDrug
Placebo control condition
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Given once, followed by observation for up to 4 hours in a progressively cold water challenge Receives: Drug: Placebo |
| 100 mg Mirabegron | Experimental | Given once, followed by observation for up to 4 hours in a progressively cold water challenge Receives: Drug: Mirabegron |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through session completion, up to 4 hours
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Through session completion, up to 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start19 Jul 2023
- Primary completion23 Apr 2024
- Study completion23 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Resting Energy ExpenditureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Office of Naval Research (ONR)
- Responsible party
- Principal investigator, Blair D. Johnson, PhD, Indiana University
- Investigators
- Blair D Johnson, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05990387
- Sponsor's protocol ID
- 2011690870; Aim 2
- Status last verified
- Jul 2025
- First submitted
- 4 Aug 2023
- Last updated
- 3 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mirabegron and Physiological Function in Cold Environments - Aim 1
- ClinicalTrials.gov ID
- NCT05990387
- Acronym / sponsor ID
- 2011690870; Aim 2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Office of Naval Research (ONR)
- Study start
- 19 Jul 2023 (actual)
- Primary completion
- 23 Apr 2024 (actual)
- Study completion
- 23 Apr 2024 (actual)
- First posted
- 14 Aug 2023 (actual)
- Results
- Posted 3 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboGiven once, followed by observation for up to 4 hours in a progressively cold water challenge |
| 100 mg Mirabegron | Experimental | Drug: MirabegronGiven once, followed by observation for up to 4 hours in a progressively cold water challenge |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- diagnosed autonomic disease
- diagnosed cardiovascular disease
- diagnosed metabolic disease
- diagnosed neurologic disease
- diagnosed endocrine disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MirabegronAlso: MyrbetriqDose-response effect on thermogenesis | Drug | 100 mg Mirabegron |
| PlaceboPlacebo control condition | Drug | Placebo |
Primary outcome
Cold Temperature Deflection Point
Time frame: Through session completion, up to 4 hours
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.
3 secondary outcomes
Thermogenesis - Oxygen Consumption
Time frame: Through session completion, up to 4 hours
Shivering Inflection Point - Surface Mechanomyography
Time frame: Through session completion, up to 4 hours
Shivering Inflection Point - Bedside Shivering Scale
Time frame: Through session completion, up to 4 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Blair D Johnson, PhD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mirabegron in people with Resting Energy Expenditure and Thermogenesis, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cold Temperature Deflection Point (time frame: Through session completion, up to 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.