Trial Outcomes & Findings for MIrabegron and Physiological Function in Cold Environments (NCT NCT05990387)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Through session completion, up to 4 hours

Results posted on

2025-07-03

Participant Flow

This is a repeated measures study design. 17 subjects provided written informed consent and were randomized. Of these subjects, 12 completed both arms of the study and 5 withdrew voluntarily (3 provided no reason for voluntarily withdrawing, 1 had a minor illness not related to the study prior to participation and chose to voluntarily withdraw, 1 voluntarily withdrew due to concerns about taking a medication).

Participant milestones

Participant milestones
Measure	Placebo First, Then Mirabegron Placebo (two encapsulated placebo tablets) was given once followed by observation for up to 4 hours in a progressive cold water challenge. This was followed by a 10 day washout period. Then, mirabegron (two 50 mg encapsulated mirabegron tablets) was given once followed by observation for up to 4 hours in a progressive cold water challenge.	Mirabegron First, Then Placebo Mirabegron (two 50 mg encapsulated mirabegron tablets) was given once followed by observation for up to 4 hours in a progressive cold water challenge. This was followed by a 10 day washout period. Then, placebo (two encapsulated placebo tablets) was given once followed by observation for up to 4 hours in a progressive cold water challenge.
Informed Consent/Screening Visit STARTED	8	9
Informed Consent/Screening Visit COMPLETED	5	7
Informed Consent/Screening Visit NOT COMPLETED	3	2
Interventions STARTED	5	7
Interventions COMPLETED	5	7
Interventions NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo First, Then Mirabegron Placebo (two encapsulated placebo tablets) was given once followed by observation for up to 4 hours in a progressive cold water challenge. This was followed by a 10 day washout period. Then, mirabegron (two 50 mg encapsulated mirabegron tablets) was given once followed by observation for up to 4 hours in a progressive cold water challenge.	Mirabegron First, Then Placebo Mirabegron (two 50 mg encapsulated mirabegron tablets) was given once followed by observation for up to 4 hours in a progressive cold water challenge. This was followed by a 10 day washout period. Then, placebo (two encapsulated placebo tablets) was given once followed by observation for up to 4 hours in a progressive cold water challenge.
Informed Consent/Screening Visit Withdrawal by Subject	3	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=12 Participants Given once, followed by observation for up to 4 hours in a progressive cold water challenge Placebo: Placebo control condition Mirabegron: 100 mg of mirabegron condition
Age, Categorical <=18 years	0 Participants n=12 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=12 Participants
Age, Categorical >=65 years	0 Participants n=12 Participants
Age, Continuous	25 years STANDARD_DEVIATION 6 • n=12 Participants
Sex: Female, Male Female	6 Participants n=12 Participants
Sex: Female, Male Male	6 Participants n=12 Participants
Region of Enrollment United States	12 participants n=12 Participants
Body Mass Index	26 kg/m^2 STANDARD_DEVIATION 5 • n=12 Participants

PRIMARY outcome

Timeframe: Through session completion, up to 4 hours

Population: Segmental analysis was unable to identify a deflection point in 4 subjects in the placebo and 4 subjects in the 100 mg Mirabegron conditions.

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.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Given once, followed by observation for up to 4 hours in a progressively cold water challenge Placebo: Placebo control condition	100 mg Mirabegron n=8 Participants Given once, followed by observation for up to 4 hours in a progressively cold water challenge Mirabegron: Dose-response effect on thermogenesis
Cold Temperature Deflection Point	22.8 degrees Celsius Standard Deviation 5.67	22.97 degrees Celsius Standard Deviation 7.42

SECONDARY outcome

Timeframe: Through session completion, up to 4 hours

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Given once, followed by observation for up to 4 hours in a progressively cold water challenge Placebo: Placebo control condition	100 mg Mirabegron n=12 Participants Given once, followed by observation for up to 4 hours in a progressively cold water challenge Mirabegron: Dose-response effect on thermogenesis
Thermogenesis - Oxygen Consumption	7.2 ml of oxygen / min / kg of body mass Standard Deviation 3.1	7.6 ml of oxygen / min / kg of body mass Standard Deviation 3.3

SECONDARY outcome

Timeframe: Through session completion, up to 4 hours

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Given once, followed by observation for up to 4 hours in a progressively cold water challenge Placebo: Placebo control condition	100 mg Mirabegron n=12 Participants Given once, followed by observation for up to 4 hours in a progressively cold water challenge Mirabegron: Dose-response effect on thermogenesis
Shivering Inflection Point - Surface Mechanomyography	24.1 degrees Celsius Standard Deviation 2.8	22.7 degrees Celsius Standard Deviation 3.6

SECONDARY outcome

Timeframe: Through session completion, up to 4 hours

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Given once, followed by observation for up to 4 hours in a progressively cold water challenge Placebo: Placebo control condition	100 mg Mirabegron n=12 Participants Given once, followed by observation for up to 4 hours in a progressively cold water challenge Mirabegron: Dose-response effect on thermogenesis
Shivering Inflection Point - Bedside Shivering Scale	22.1 degrees celsius Standard Deviation 2.5	19.8 degrees celsius Standard Deviation 3.9

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

100 mg Mirabegron

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Blair Johnson

Indiana University

Phone: 8128558699

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place