Resting Energy ExpenditurePhase 1/2NCT04766021
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
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2021to 27 Apr 2023
- 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 which dose of mirabegron administration will increase thermogenesis during 6 hours of a mild cold stress 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 5 visits to the laboratory; one informed consent/screening visit and 4 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 be instrumented for skin temperature (12-sites: calf, shin, front of the thigh, back of the thigh, chest, upper back, forehead, lower back, abdomen, forearm, hand, and foot; iButtons) core temperature (rectal thermistor), indices of shivering (surface mechanomyography using triaxial accelerometers at 3 anatomic sites (chest, upper back, and thigh) and the bedside shivering assessment scale), brachial artery blood pressure (brachial artery auscultation), and heart rate (3-lead ECG). Thermal perceptions will be assessed using Likert scales for thermal discomfort and thermal sensation. Participants will be shirtless (sports bra for women) and will wear shorts throughout the study. After 20 minutes of quiet resting in the supine position, 5 minutes of baseline measurements will be taken, thermal perceptions and an infrared thermography image of the supraclavicular fossa will be obtained as an indicator of brown adipose tissue activation (6), and a whole blood sample will be obtained.
Participants will then ingest mirabegron (100 mg, 150 mg, or 200 mg) or placebo. Thirty minutes after mirabegron or placebo has been ingested, participants will enter the whole-body indirect calorimeter; the internal temperature of the calorimeter will be set to 20 degrees C (68 degrees F). This will elicit a mild cold stress over the 6 hours of observation in the whole-body indirect calorimeter. The whole-body indirect calorimeter provides an accurate and continuous measure of thermogenesis (in the form of energy expenditure) that can be used over long periods of time in a stable environment. The whole-body calorimeter is designed to perform human studies that are up to 48 hours in duration and contains a private washroom. While in the whole-body indirect calorimeter, participants will be instructed to be sedentary and will be allowed to watch television or read. In order to stay consistent between study visits, participants will be instructed to spend the same amount of time watching television or reading for each study visit. Every 30 minutes, we will record skin temperatures, core temperature, blood pressure, and heart rate. Thermogenesis will be determined by having participants lie supine for 30 minutes and resting energy expenditure will be calculated using the abbreviated Weir formula every hour (5). Thermal perceptions and an infrared thermography image will also be obtained at these time points. At approximately the midpoint of the 6-hour measurement period, participants will have the opportunity to use the restroom and an additional urine sample will be collected at this time. At the end of the 6-hour measurement period, participants will exit the whole-body indirect calorimeter and final measurements of skin temperature, core temperature, heart rate, and blood pressure will be obtained as well as a final infrared thermography image and a whole blood sample. After the experiment is complete, participants will be given a mylar blanket to re-warm themselves prior to leaving the laboratory.
Participants will be asked to return to the laboratory after 10-14 days to repeat the experiment until all 4 dosing conditions (placebo, 100 mg, 150 mg, and 200 mg of mirabegron) have been tested. Each participant's order of assignment to placebo or drug dosing over the 4 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 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room Receives: Drug: Placebo |
| 100 mg Mirabegron | Experimental | Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room Receives: Drug: Mirabegron |
| 150 mg Mirabegron | Experimental | Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room Receives: Drug: Mirabegron |
| 200 mg Mirabegron | Experimental | Given once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room Receives: Drug: Mirabegron |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Resting Energy Expenditure
The cumulative resting energy expenditure will be calculated to reflect the cumulative effect of mirabegron over time.
Measured: 360 minutes
Secondary outcomes (9)
Core Body Temperature
Core Body temperature will be measured via rectal temperature during the experiment. The mean value was calculated.
Measured: Baseline and every 30 minutes through 360 minutes
Brown Adipose Tissue Activation
Infrared thermography will be used to measure supraclavicular skin temperature as an estimate of brown adipose tissue activation. The mean value was calculated.
Measured: Baseline and hourly through 360 minutes
Weighted Mean Skin Temperature
Fourteen iButtons will be adhered to the skin using adhesive tape on the calf, shin, front thigh, back thigh, foot, chest, upper back, lower back, forearm, hand, forehead, fingertip, toetip, and abdomen area to measure weighted skin temperature. Temperature readings will be taken every 30 minutes during the experiment. The mean value was calculated.
Measured: Baseline and every 30 minutes through 360 minutes
Heart Rate
Heart rate will be obtained using a 3-lead electrocardiogram. The mean value was calculated.
Measured: Baseline and every 30 minutes through 360 minutes
Mean Arterial Pressure
Blood pressure will be monitored using a cuff placed on the upper arm that is inflated and deflated periodically. The mean value was calculated.
Measured: Baseline and every 30 minutes through 360 minutes
Relative Oxygen Consumption
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. The mean value was calculated.
Measured: Baseline and every 30 minutes through 360 minutes
Bedside Shivering Scale
Two investigators will subjectively assess shivering by the participants using a Likert scale (range 0-3; 0 = none, 3 = Severe) and the scores will be averaged. The mean value was calculated.
Measured: Baseline and every 30 minutes through 360 minutes
Thermal Comfort Scale
Participants will complete a Likert scale to assess their thermal comfort (range: 1-4; 1 = comfortable, 4 = very uncomfortable).The mean value was calculated.
Measured: Baseline and every 30 minutes through 360 minutes
Thermal Sensation Scale
Participants will complete a Likert scale to assess their thermal sensation (range: 1-7; 1 = cold, 4 = neutral, 7 = hot). The mean value was calculated.
Measured: Baseline and every 30 minutes through 360 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2021
- Study start30 Nov 2021
- Primary completion27 Apr 2023
- Study completion27 Apr 2023
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
- 30 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
- NCT04766021
- Sponsor's protocol ID
- 2011690870; Aim 1
- Status last verified
- Jul 2024
- First submitted
- 9 Feb 2021
- Last updated
- 12 Jul 2024
- 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 12 Jul 2024. 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
- NCT04766021
- Acronym / sponsor ID
- 2011690870; Aim 1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Office of Naval Research (ONR)
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 27 Apr 2023 (actual)
- Study completion
- 27 Apr 2023 (actual)
- First posted
- 23 Feb 2021 (actual)
- Results
- Posted 12 Jul 2024
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 which dose of mirabegron administration will increase thermogenesis during 6 hours of a mild cold stress 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 5 visits to the laboratory; one informed consent/screening visit and 4 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 be instrumented for skin temperature (12-sites: calf, shin, front of the thigh, back of the thigh, chest, upper back, forehead, lower back, abdomen, forearm, hand, and foot; iButtons) core temperature (rectal thermistor), indices of shivering (surface mechanomyography using triaxial accelerometers at 3 anatomic sites (chest, upper back, and thigh) and the bedside shivering assessment scale), brachial artery blood pressure (brachial artery auscultation), and heart rate (3-lead ECG). Thermal perceptions will be assessed using Likert scales for thermal discomfort and thermal sensation. Participants will be shirtless (sports bra for women) and will wear shorts throughout the study. After 20 minutes of quiet resting in the supine position, 5 minutes of baseline measurements will be taken, thermal perceptions and an infrared thermography image of the supraclavicular fossa will be obtained as an indicator of brown adipose tissue activation (6), and a whole blood sample will be obtained.
Participants will then ingest mirabegron (100 mg, 150 mg, or 200 mg) or placebo. Thirty minutes after mirabegron or placebo has been ingested, participants will enter the whole-body indirect calorimeter; the internal temperature of the calorimeter will be set to 20 degrees C (68 degrees F). This will elicit a mild cold stress over the 6 hours of observation in the whole-body indirect calorimeter. The whole-body indirect calorimeter provides an accurate and continuous measure of thermogenesis (in the form of energy expenditure) that can be used over long periods of time in a stable environment. The whole-body calorimeter is designed to perform human studies that are up to 48 hours in duration and contains a private washroom. While in the whole-body indirect calorimeter, participants will be instructed to be sedentary and will be allowed to watch television or read. In order to stay consistent between study visits, participants will be instructed to spend the same amount of time watching television or reading for each study visit. Every 30 minutes, we will record skin temperatures, core temperature, blood pressure, and heart rate. Thermogenesis will be determined by having participants lie supine for 30 minutes and resting energy expenditure will be calculated using the abbreviated Weir formula every hour (5). Thermal perceptions and an infrared thermography image will also be obtained at these time points. At approximately the midpoint of the 6-hour measurement period, participants will have the opportunity to use the restroom and an additional urine sample will be collected at this time. At the end of the 6-hour measurement period, participants will exit the whole-body indirect calorimeter and final measurements of skin temperature, core temperature, heart rate, and blood pressure will be obtained as well as a final infrared thermography image and a whole blood sample. After the experiment is complete, participants will be given a mylar blanket to re-warm themselves prior to leaving the laboratory.
Participants will be asked to return to the laboratory after 10-14 days to repeat the experiment until all 4 dosing conditions (placebo, 100 mg, 150 mg, and 200 mg of mirabegron) have been tested. Each participant's order of assignment to placebo or drug dosing over the 4 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
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboGiven once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room |
| 100 mg Mirabegron | Experimental | Drug: MirabegronGiven once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room |
| 150 mg Mirabegron | Experimental | Drug: MirabegronGiven once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room |
| 200 mg Mirabegron | Experimental | Drug: MirabegronGiven once, followed by observation for 6 hours in a 20 degree Celsius (68 degree Fahrenheit) room |
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, 150 mg Mirabegron, 200 mg Mirabegron |
| PlaceboPlacebo control condition | Drug | Placebo |
Primary outcome
Cumulative Resting Energy Expenditure
Time frame: 360 minutes
The cumulative resting energy expenditure will be calculated to reflect the cumulative effect of mirabegron over time.
9 secondary outcomes
Core Body Temperature
Time frame: Baseline and every 30 minutes through 360 minutes
Brown Adipose Tissue Activation
Time frame: Baseline and hourly through 360 minutes
Weighted Mean Skin Temperature
Time frame: Baseline and every 30 minutes through 360 minutes
Heart Rate
Time frame: Baseline and every 30 minutes through 360 minutes
Mean Arterial Pressure
Time frame: Baseline and every 30 minutes through 360 minutes
Relative Oxygen Consumption
Time frame: Baseline and every 30 minutes through 360 minutes
Bedside Shivering Scale
Time frame: Baseline and every 30 minutes through 360 minutes
Thermal Comfort Scale
Time frame: Baseline and every 30 minutes through 360 minutes
Thermal Sensation Scale
Time frame: Baseline and every 30 minutes through 360 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2024.
- 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 12 Jul 2024. 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 12 Jul 2024). 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?
Cumulative Resting Energy Expenditure (time frame: 360 minutes). 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 12 Jul 2024.