Trial Outcomes & Findings for Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate (NCT NCT01950520)

NCT ID: NCT01950520

Last Updated: 2024-10-16

Results Overview

Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

47 participants

Primary outcome timeframe

Cohort 1: Days 1-17

Results posted on

2024-10-16

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1 Chamber temperature will be block randomized with low temperature and 27°C (Cohort 1 only) Within each block, the following five interventions will be repeated: Propranolol: Propanolol 160mg, oral, by mouth (Cohort 1 only) Pindolol: Pindolol 20mg, oral, by mouth (Cohort 1 only) Dantrolene: Dantrolene 100mg, oral, by mouth (Cohort 1 only) Magnesium Sulfate: Magnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only) Placebo Cohort 1: Placebo, oral, by mouth (Cohort 1 only)	Cohort 2 Interventions, in random order, will be administered during one of the six one-day stays Caffeine: Caffeine 200mg, oral, by mouth (Cohort 2 only) Qsymia: Qsymia (topiramate 92mg CR, phentermine 15mg PO), oral, by mouth (Cohort 2 only) Topiramate: Topiramate 200mg, oral, by mouth (Cohort 2 only) Phentermine: Phentermine 37.5mg, oral, by mouth (Cohort 2 only) Naltrexone: Naltrexone 100mg, oral, by mouth (Cohort 2 only) Placebo Cohort 2: Placebo, oral, by mouth (Cohort 2 only)	Cohort 3 Interventions, in random order, will be administered during one of the four overnight inpatient stays Mirabegron 50mg: Mirabegron 50mg, oral, by mouth (Cohort 3 only) Mirabegron 200mg: Mirabegron 200mg, oral, by mouth (Cohort 3 only) Placebo for Mirabegron: Placebo for Mirabegron, oral, by mouth (Cohort 3 only)
Overall Study STARTED	16	18	13
Overall Study COMPLETED	16	17	12
Overall Study NOT COMPLETED	0	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=16 Participants Chamber temperature will be block randomized with low temperature and 27C (Cohort 1 only) Within each block, the following five interventions will be repeated: Propranolol: Propanolol 160mg, oral, by mouth (Cohort 1 only) Pindolol: Pindolol 20mg, oral, by mouth (Cohort 1 only) Dantrolene: Dantrolene 100mg, oral, by mouth (Cohort 1 only) Magnesium Sulfate: Magnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only) Placebo Cohort 1: Placebo, oral, by mouth (Cohort 1 only)	Cohort 2 n=18 Participants Interventions, in random order, will be administered during one of the six one-day stays Caffeine: Caffeine 200mg, oral, by mouth (Cohort 2 only) Qsymia: Qsymia (topiramate 92mg CR, phentermine 15mg PO), oral, by mouth (Cohort 2 only) Topiramate: Topiramate 200mg, oral, by mouth (Cohort 2 only) Phentermine: Phentermine 37.5mg, oral, by mouth (Cohort 2 only) Naltrexone: Naltrexone 100mg, oral, by mouth (Cohort 2 only) Placebo Cohort 2: Placebo, oral, by mouth (Cohort 2 only)	Cohort 3 n=13 Participants Interventions, in random order, will be administered during one of the four overnight inpatient stays Mirabegron 50mg: Mirabegron 50mg, oral, by mouth (Cohort 3 only) Mirabegron 200mg: Mirabegron 200mg, oral, by mouth (Cohort 3 only) Placebo for Mirabegron: Placebo for Mirabegron, oral, by mouth (Cohort 3 only)	Total n=47 Participants Total of all reporting groups
Age, Continuous	26 years STANDARD_DEVIATION 4.6 • n=5 Participants	28.1 years STANDARD_DEVIATION 4 • n=7 Participants	25.1 years STANDARD_DEVIATION 4.6 • n=5 Participants	26.5 years STANDARD_DEVIATION 4.5 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	18 Participants n=7 Participants	13 Participants n=5 Participants	47 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	11 Participants n=7 Participants	7 Participants n=5 Participants	27 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Cohort 1: Days 1-17

Population: Cohort 1

Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.

Outcome measures

Outcome measures
Measure	Cohort 1 n=16 Participants Chamber temperature will be block randomized with low temperature (Cohort 1 only) Within each block, the following five interventions will be repeated: Propranolol: Propanolol 160mg, oral, by mouth (Cohort 1 only) Pindolol: Pindolol 20mg, oral, by mouth (Cohort 1 only) Dantrolene: Dantrolene 100mg, oral, by mouth (Cohort 1 only) Magnesium Sulfate: Magnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only) Placebo Cohort 1: Placebo, oral, by mouth (Cohort 1 only)
Resting Energy Expenditure at Low Temperature Placebo Cohort 1	1.277 kcal/min Standard Deviation 0.151
Resting Energy Expenditure at Low Temperature Propranolol	1.134 kcal/min Standard Deviation 0.109
Resting Energy Expenditure at Low Temperature Dantrolene	1.300 kcal/min Standard Deviation 0.118
Resting Energy Expenditure at Low Temperature Magnesium sulfate	1.271 kcal/min Standard Deviation 0.126
Resting Energy Expenditure at Low Temperature Pindolol	1.165 kcal/min Standard Deviation 0.112

PRIMARY outcome

Timeframe: Cohorts 2: Six one-day overnight inpatient stays over a six to twelve week period.

Population: missed visits due to Covid etc.

Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.

Outcome measures

Outcome measures
Measure	Cohort 1 n=18 Participants Chamber temperature will be block randomized with low temperature (Cohort 1 only) Within each block, the following five interventions will be repeated: Propranolol: Propanolol 160mg, oral, by mouth (Cohort 1 only) Pindolol: Pindolol 20mg, oral, by mouth (Cohort 1 only) Dantrolene: Dantrolene 100mg, oral, by mouth (Cohort 1 only) Magnesium Sulfate: Magnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only) Placebo Cohort 1: Placebo, oral, by mouth (Cohort 1 only)
Resting Energy Expenditure at Low Temperature Caffeine	1.292 kcal/min Standard Deviation 0.123
Resting Energy Expenditure at Low Temperature Phentermine	1.217 kcal/min Standard Deviation 0.116
Resting Energy Expenditure at Low Temperature Topiramate	1.191 kcal/min Standard Deviation 0.122
Resting Energy Expenditure at Low Temperature Qsymia	1.228 kcal/min Standard Deviation 0.122
Resting Energy Expenditure at Low Temperature Naltrexone	1.185 kcal/min Standard Deviation 0.140
Resting Energy Expenditure at Low Temperature Placebo	1.215 kcal/min Standard Deviation 0.109

PRIMARY outcome

Timeframe: Cohort 3: Four one-day overnight inpatient stays over a 12-week period.

Population: missed visits due to Covid etc.

Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.

Outcome measures

Outcome measures
Measure	Cohort 1 n=12 Participants Chamber temperature will be block randomized with low temperature (Cohort 1 only) Within each block, the following five interventions will be repeated: Propranolol: Propanolol 160mg, oral, by mouth (Cohort 1 only) Pindolol: Pindolol 20mg, oral, by mouth (Cohort 1 only) Dantrolene: Dantrolene 100mg, oral, by mouth (Cohort 1 only) Magnesium Sulfate: Magnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only) Placebo Cohort 1: Placebo, oral, by mouth (Cohort 1 only)
Resting Energy Expenditure at Low Temperature Placebo for Mirabegron	1.25 kcal/min Standard Deviation 0.39
Resting Energy Expenditure at Low Temperature Mirabegron 50mg	1.31 kcal/min Standard Deviation 0.19
Resting Energy Expenditure at Low Temperature Mirabegron 200mg	1.37 kcal/min Standard Deviation 0.19

PRIMARY outcome

Timeframe: Cohort 1: Days 1-17

Population: Cohort 1

Basal metabolic rate (BMR) is the resting energy expenditure (REE) at thermoneutrality (27c).

Outcome measures

Outcome measures
Measure	Cohort 1 n=16 Participants Chamber temperature will be block randomized with low temperature (Cohort 1 only) Within each block, the following five interventions will be repeated: Propranolol: Propanolol 160mg, oral, by mouth (Cohort 1 only) Pindolol: Pindolol 20mg, oral, by mouth (Cohort 1 only) Dantrolene: Dantrolene 100mg, oral, by mouth (Cohort 1 only) Magnesium Sulfate: Magnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only) Placebo Cohort 1: Placebo, oral, by mouth (Cohort 1 only)
Basal Metabolic Rate Placebo Cohort 1	1.153 kcal/min Standard Deviation 0.098
Basal Metabolic Rate Propranolol	1.053 kcal/min Standard Deviation 0.099
Basal Metabolic Rate Dantrolene	1.143 kcal/min Standard Deviation 0.105
Basal Metabolic Rate Magnesium sulfate	1.108 kcal/min Standard Deviation 0.124
Basal Metabolic Rate Pindolol	1.116 kcal/min Standard Deviation 0.109

PRIMARY outcome

Timeframe: Cohort 3: Four one-day overnight inpatient stays over a 12-week period.

Population: missed visits due to Covid etc.

Brown adipose tissue (BAT) activity is a quantification of tissue volume and metabolic activity per unit volume.