Healthy VolunteersPhase 2NCT01950520

Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate

A Phase 2 study testing Propranolol, Pindolol and Dantrolene in people with Healthy Volunteers, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Background: Changes in how a person's body burns energy or calories can affect their weight over time. The lowest level of energy the body needs to function is called basal metabolic rate. In the cold, we burn extra energy, even before we start to shiver. Read more about this study

Who is it for?: Ages 18 to 35 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: Propranolol, Pindolol and Dantrolene
Type of treatment: Pill or oral medicine, Injection or infusion, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 47 participants
Where: 1 siteUnited States
Study dates: 7 Feb 2014to 11 Jun 2024
Phase: Phase 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 35 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

Generally healthy
Males between the age 18-35 years
Written informed consent.

Who cannot join

BMI less than 18.5 or greater than 25.0 kg/M(2)
History of cardiovascular disease such as congestive heart failure, heart block, clinically abnormal EKG as determined by investigators
History of liver disease or ALT serum level greater than two times the laboratory upper limit of normal
History of kidney diseases or renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min (MDRD equation)
History of cancer or bariatric surgery
History of diabetes mellitus or fasting serum glucose > 126 mg/dL

Show all 24Show fewer

History of hypo- or hyper-thyroid or abnormal TSH, except minor deviations deemed to be of no clinical significance by the investigator.
History of asthma, chronic obstructive pulmonary disease and glaucoma
Psychological conditions, such as (but not limited to) claustrophobia, clinical depression, bipolar disorders, that would be incompatible with safe and successful participation in this study
Weight change >5 percent in the past 6 months or a trained athlete
Blood pressure greater than 140/90 mmHg or current antihypertensive therapy
Iron deficiency (Hemoglobin <13.7 g/dL and Hematocrit <40.1%)
History of illicit drug, opioids, or alcohol abuse within the last 5 years; current use of drugs (by history) or alcohol (CAGE greater than or equal to 2) (95)
Current use of medications/dietary supplements/alternative therapies known to alter energy metabolism
Current medications that may have interactions with study drugs as determined by the investigators
History of adverse or allergic reactions to the study drugs
Daily caffeine intake >500 mg (about 4 cups) and have withdrawal symptoms
Current smoker or user of tobacco products
Cannot commit to the schedule of visits to the Clinical Research Center (CRC) as required by the study timeline
Have had previous radiation exposure within the last year (X-rays, PET scans, etc.) that would exceed research limits (please let us know if you have received radiation for research purposes)
Have inflexible dietary restrictions
Any other reason that the investigator thinks would make interpretation of the study results difficult.
For subjects having an MRD (cOHORT 3), history of pacemaker, metallic heart valves, aneurysm clip, pedicle screws, metallic foreign body in eye, or other metallic implant.
For subjects receiving mirabegron (Cohort 3), a diagnosis of bladder outlet obstruction or the use of antimuscarinic medications for the treatment of overactive bladder.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: The Mechanism of Human Non-Shivering Thermogenesis and Basal Metabolic Rate

Background:

Changes in how a person's body burns energy or calories can affect their weight over time. The lowest level of energy the body needs to function is called basal metabolic rate. In the cold, we burn extra energy, even before we start to shiver. This is called non-shivering thermogenesis and it occurs in different types of tissue such as muscle and fat. Researchers want to learn more about this type of energy burning and how it is regulated. They hope this will help treat obesity in the future.

Objectives:

Sub-study 1: to better understand how non-shivering thermogenesis works.
Sub-study 2: to measure the effects of anti-obesity drugs on basal metabolic rate.
Sub-study 3: to better understand the effects of mirabegron, a beta-3 adrenergic receptor agonist, on brown fat activity.

Eligibility:

Healthy, lean adult males ages 18 to 35.

Design:

Participants will be screened with medical history, physical exam, blood test, and EKG.
For sub-studies 1 and 2:
Participants will receive one X-ray scan.
Each day, all participants will:
Have height and weight measured, and have urine collected.
Spend 4 hours in a temperature-controlled room with furniture, toilet area, phone, and computer. They will wear small non-invasive devices to monitor activity, heart rate, temperature, and shivering.
Walk for 30 minutes.
For sub-study 3:
Participants will receive one DXA scan and up to 4 PET/CT scans and 4 MRIs
Each stay, all participants will:
Have height and weight measured, and have urine collected.
Spend 6 hours in a temperature-controlled room with furniture, toilet area, phone, and computer. They will wear small non-invasive devices to monitor activity, heart rate, temperature, and shivering.
Participants will be compensated for their time and participation at the end of the study

Read the detailed description

The balance between energy expenditure (EE) and energy intake ultimately determines body weight. Resting EE is the major component (60-75%) of total EE in an adult human being. Resting EE dynamically adapts to environmental changes such as ambient temperature. In our on-going study of environmental temperature changes within and around the thermoneutral zone, we observed that healthy young men can increase EE by 17 % of the basal metabolic rate through the process of non-shivering thermogenesis (NST). This capacity for NST is unexpectedly large as compared to prior reports of mild cold-induced thermogenesis (3 to 11%) and suggests that increasing NST could be explored as an intervention to combat obesity.

The aim of this study is to better understand the physiology of NST and to develop improved assays for evaluating the effect of drugs that alter EE. For example, only recently has it been realized that brown adipose tissue (BAT) is functional in adult humans and that white adipose tissue can be converted to brown-adipose-like tissue to increase heat production during cold exposures. Moreover, skeletal muscle likely also plays a role in cold-induced thermogenesis even before overt shivering occurs. It is plausible that the mechanisms governing heat production for NST contribute to regulation of body weight and thus may be contributing to the current obesity epidemic: even small changes in EE, if not compensated by changes in food intake, can have long-term effects on body weight.

This protocol has two phases. The first uses a pharmacologic approach to investigate the mechanism of NST in young healthy lean males. Since the principal physiologic stimulus to BAT (and possibly muscle for NST) is via the sympathetic nervous system (SNS), beta-adrenergic receptors may hold key roles in regulating human EE. We hypothesize that, by careful measurements of NST (at an individually-titrated cool environmental temperature, between 18 21 degrees C vs. at thermoneutrality of 27 degrees C) and using beta-adrenergic drugs that differ in receptor specificity and agonist/antagonist properties, we will gain better understanding of the regulation of human NST.

The second phase of the study focuses on measuring of FDA-approved drugs (such as anti-obesity drugs) potential effect on basal metabolic rate (BMR) under thermoneutral conditions. The rationale is that previous studies of drug effect on EE in humans have not always rigorously enforced the use of thermoneutral conditions, thus may have increased variability and underestimated the effect, contributing to inconclusive findings.

It is envisioned that this study will further our knowledge of the mechanisms that regulate the acute adaptive changes in resting energy expenditure and the effects of drug therapy targeting obesity in humans.

Conditions: Healthy Volunteers
Being tested: Propranolol, Pindolol, Dantrolene, Magnesium Sulfate, Caffeine
Keywords: Adipose Tissue, Adult, Resting Energy Expenditure, RESPIRATORY QUOTIENT, BASAL METABOLIC RATE

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PropranololDrug
Propanolol 160mg, oral, by mouth (Cohort 1 only)
PindololDrug
Pindolol 20mg, oral, by mouth (Cohort 1 only)
DantroleneDrug
Dantrolene 100mg, oral, by mouth (Cohort 1 only)
Magnesium SulfateDrug
Magnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only)
CaffeineDrug
Caffeine 200mg, oral, by mouth (Cohort 2 only)
QsymiaDrug
Qsymia (topiramate 92mg CR, phentermine 15mg PO), oral, by mouth (Cohort 2 only)
TopiramateDrug
Topiramate 200mg, oral, by mouth (Cohort 2 only)
PhentermineBehavioural
Phentermine 37.5mg, oral, by mouth (Cohort 2 only)
NaltrexoneDrug
Naltrexone 100mg, oral, by mouth (Cohort 2 only)
Mirabegron 50mgDrug
Mirabegron 50mg, oral, by mouth (Cohort 3 only)
Mirabegron 200mgDrug
Mirabegron 200mg, oral, by mouth (Cohort 3 only)
Placebo Cohort 1Drug
Placebo, oral, by mouth (Cohort 1 only)
Placebo Cohort 2Drug
Placebo, oral, by mouth (Cohort 2 only)
Placebo for MirabegronDrug
Placebo for Mirabegron, oral, by mouth (Cohort 3 only)

Study groups in NCT01950520
Study group	Role	What they receive
Cohort 1	Experimental	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) Receives: Drug: Propranolol; Drug: Pindolol; Drug: Dantrolene; Drug: Magnesium Sulfate; Drug: Placebo Cohort 1
Cohort 2	Experimental	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) Receives: Drug: Caffeine; Drug: Qsymia; Drug: Topiramate; Behavioral: Phentermine; Drug: Naltrexone; Drug: Placebo Cohort 2
Cohort 3	Experimental	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) Receives: Drug: Mirabegron 50mg; Drug: Mirabegron 200mg; Drug: Placebo for Mirabegron

What is being measured

The primary outcome is the main question the study is designed to answer.

Resting Energy Expenditure at Low Temperature
Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.
Measured: Cohort 1: Days 1-17
Resting Energy Expenditure at Low Temperature
Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.
Measured: Cohorts 2: Six one-day overnight inpatient stays over a six to twelve week period.
Resting Energy Expenditure at Low Temperature
Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.
Measured: Cohort 3: Four one-day overnight inpatient stays over a 12-week period.
Basal Metabolic Rate
Basal metabolic rate (BMR) is the resting energy expenditure (REE) at thermoneutrality (27c).
Measured: Cohort 1: Days 1-17
Brown Adipose Tissue Activity (Cohort 3 Only)
Brown adipose tissue (BAT) activity is a quantification of tissue volume and metabolic activity per unit volume.
Measured: Cohort 3: Four one-day overnight inpatient stays over a 12-week period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Feb 201411 Jun 2024

First posted25 Sep 2013 (estimated)
Study start7 Feb 2014
Primary completion17 Dec 2022
Study completion11 Jun 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.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
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 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01950520
Sponsor's protocol ID: 130200
Other IDs: 13-DK-0200
Status last verified: 11 Jun 2024
First submitted: 21 Sep 2013
Last updated: 16 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: .All IPD that underlie results in a publication

Publications

Cannon B, Nedergaard J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol. 2011 Jan 15;214(Pt 2):242-53. doi: 10.1242/jeb.050989.
PubMed 21177944
van Marken Lichtenbelt WD, Schrauwen P. Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol. 2011 Aug;301(2):R285-96. doi: 10.1152/ajpregu.00652.2010. Epub 2011 Apr 13.
PubMed 21490370
Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52. doi: 10.1152/ajpendo.00691.2006. Epub 2007 May 1.
PubMed 17473055
Baskin AS, Linderman JD, Brychta RJ, McGehee S, Anflick-Chames E, Cero C, Johnson JW, O'Mara AE, Fletcher LA, Leitner BP, Duckworth CJ, Huang S, Cai H, Garraffo HM, Millo CM, Dieckmann W, Tolstikov V, Chen EY, Gao F, Narain NR, Kiebish MA, Walter PJ, Herscovitch P, Chen KY, Cypess AM. Regulation of Human Adipose Tissue Activation, Gallbladder Size, and Bile Acid Metabolism by a beta3-Adrenergic Receptor Agonist. Diabetes. 2018 Oct;67(10):2113-2125. doi: 10.2337/db18-0462. Epub 2018 Jul 6.
PubMed 29980535

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Mechanism of Human Non-Shivering Thermogenesis and Basal Metabolic Rate
ClinicalTrials.gov ID: NCT01950520
Acronym / sponsor ID: 130200
Conditions: Healthy Volunteers
Keywords: Adipose Tissue, Adult, Resting Energy Expenditure, RESPIRATORY QUOTIENT, BASAL METABOLIC RATE
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
Study start: 7 Feb 2014 (actual)
Primary completion: 17 Dec 2022 (actual)
Study completion: 11 Jun 2024 (actual)
First posted: 25 Sep 2013 (estimated)
Results: Posted 16 Oct 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Changes in how a person's body burns energy or calories can affect their weight over time. The lowest level of energy the body needs to function is called basal metabolic rate. In the cold, we burn extra energy, even before we start to shiver. This is called non-shivering thermogenesis and it occurs in different types of tissue such as muscle and fat. Researchers want to learn more about this type of energy burning and how it is regulated. They hope this will help treat obesity in the future.

Objectives:

Sub-study 1: to better understand how non-shivering thermogenesis works.
Sub-study 2: to measure the effects of anti-obesity drugs on basal metabolic rate.
Sub-study 3: to better understand the effects of mirabegron, a beta-3 adrenergic receptor agonist, on brown fat activity.

Eligibility:

Healthy, lean adult males ages 18 to 35.

Design:

Participants will be screened with medical history, physical exam, blood test, and EKG.
For sub-studies 1 and 2:
Participants will receive one X-ray scan.
Each day, all participants will:
Have height and weight measured, and have urine collected.
Spend 4 hours in a temperature-controlled room with furniture, toilet area, phone, and computer. They will wear small non-invasive devices to monitor activity, heart rate, temperature, and shivering.
Walk for 30 minutes.
For sub-study 3:
Participants will receive one DXA scan and up to 4 PET/CT scans and 4 MRIs
Each stay, all participants will:
Have height and weight measured, and have urine collected.
Spend 6 hours in a temperature-controlled room with furniture, toilet area, phone, and computer. They will wear small non-invasive devices to monitor activity, heart rate, temperature, and shivering.
Participants will be compensated for their time and participation at the end of the study

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Cohort 1	Experimental	Drug: Propranolol, Drug: Pindolol, Drug: Dantrolene, Drug: Magnesium Sulfate, Drug: Placebo Cohort 1Chamber 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	Experimental	Drug: Caffeine, Drug: Qsymia, Drug: Topiramate, Behavioral: Phentermine, Drug: Naltrexone, Drug: Placebo Cohort 2Interventions, 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	Experimental	Drug: Mirabegron 50mg, Drug: Mirabegron 200mg, Drug: Placebo for MirabegronInterventions, 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)

Who may qualify

Ages: 18 to 35 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Generally healthy
Males between the age 18-35 years
Written informed consent.

Key exclusion criteria (24 listed)

BMI less than 18.5 or greater than 25.0 kg/M(2)
History of cardiovascular disease such as congestive heart failure, heart block, clinically abnormal EKG as determined by investigators
History of liver disease or ALT serum level greater than two times the laboratory upper limit of normal
History of kidney diseases or renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min (MDRD equation)
History of cancer or bariatric surgery

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
PropranololPropanolol 160mg, oral, by mouth (Cohort 1 only)	Drug	Cohort 1
PindololPindolol 20mg, oral, by mouth (Cohort 1 only)	Drug	Cohort 1
DantroleneDantrolene 100mg, oral, by mouth (Cohort 1 only)	Drug	Cohort 1
Magnesium SulfateMagnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only)	Drug	Cohort 1
CaffeineCaffeine 200mg, oral, by mouth (Cohort 2 only)	Drug	Cohort 2
QsymiaQsymia (topiramate 92mg CR, phentermine 15mg PO), oral, by mouth (Cohort 2 only)	Drug	Cohort 2
TopiramateTopiramate 200mg, oral, by mouth (Cohort 2 only)	Drug	Cohort 2
PhenterminePhentermine 37.5mg, oral, by mouth (Cohort 2 only)	Behavioural	Cohort 2
NaltrexoneNaltrexone 100mg, oral, by mouth (Cohort 2 only)	Drug	Cohort 2
Mirabegron 50mgMirabegron 50mg, oral, by mouth (Cohort 3 only)	Drug	Cohort 3
Mirabegron 200mgMirabegron 200mg, oral, by mouth (Cohort 3 only)	Drug	Cohort 3
Placebo Cohort 1Placebo, oral, by mouth (Cohort 1 only)	Drug	Cohort 1
Placebo Cohort 2Placebo, oral, by mouth (Cohort 2 only)	Drug	Cohort 2
Placebo for MirabegronPlacebo for Mirabegron, oral, by mouth (Cohort 3 only)	Drug	Cohort 3

Primary outcome

Resting Energy Expenditure at Low Temperature
Time frame: Cohort 1: Days 1-17
Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.
Resting Energy Expenditure at Low Temperature
Time frame: Cohorts 2: Six one-day overnight inpatient stays over a six to twelve week period.
Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.
Resting Energy Expenditure at Low Temperature
Time frame: Cohort 3: Four one-day overnight inpatient stays over a 12-week period.
Resting energy expenditure (REE) at a temperature just above the subject's placebo shivering threshold.
Basal Metabolic Rate
Time frame: Cohort 1: Days 1-17
Basal metabolic rate (BMR) is the resting energy expenditure (REE) at thermoneutrality (27c).
Brown Adipose Tissue Activity (Cohort 3 Only)
Time frame: Cohort 3: Four one-day overnight inpatient stays over a 12-week period.
Brown adipose tissue (BAT) activity is a quantification of tissue volume and metabolic activity per unit volume.

Results and safety

Results posted to the registry on 16 Oct 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1	16	16
Cohort 2	18	17
Cohort 3	13	12

Primary outcome: Resting Energy Expenditure at Low Temperature

Time frame: Cohort 1: Days 1-17. Mean (Standard Deviation). Unit: kcal/min

Measure	Cohort 1 n = 16
Placebo Cohort 1	1.277 (0.151)
Propranolol	1.134 (0.109)
Dantrolene	1.300 (0.118)
Magnesium sulfate	1.271 (0.126)
Pindolol	1.165 (0.112)

Population analysed: Cohort 1

Primary outcome: Resting Energy Expenditure at Low Temperature

Time frame: Cohorts 2: Six one-day overnight inpatient stays over a six to twelve week period.. Mean (Standard Deviation). Unit: kcal/min

Measure	Cohort 2 n = 18
Caffeine	1.292 (0.123)
Phentermine	1.217 (0.116)
Topiramate	1.191 (0.122)
Qsymia	1.228 (0.122)
Naltrexone	1.185 (0.140)
Placebo	1.215 (0.109)

Population analysed: missed visits due to Covid etc.

Primary outcome: Resting Energy Expenditure at Low Temperature

Time frame: Cohort 3: Four one-day overnight inpatient stays over a 12-week period.. Mean (Standard Deviation). Unit: kcal/min

Measure	Cohort 3 n = 12
Placebo for Mirabegron	1.25 (0.39)
Mirabegron 50mg	1.31 (0.19)
Mirabegron 200mg	1.37 (0.19)

Population analysed: missed visits due to Covid etc.

Primary outcome: Basal Metabolic Rate

Time frame: Cohort 1: Days 1-17. Mean (Standard Deviation). Unit: kcal/min

Measure	Cohort 1 n = 16
Placebo Cohort 1	1.153 (0.098)
Propranolol	1.053 (0.099)
Dantrolene	1.143 (0.105)
Magnesium sulfate	1.108 (0.124)
Pindolol	1.116 (0.109)

Population analysed: Cohort 1

Adverse events

Time frame: Twelve weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 Low Temperature : Placebo	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Cohort 1 Low Temperature : Proprannolol	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Cohort 1 Low Temperature : Dantrolene	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Cohort 1 Low Temperature : Magnesium	0 of 16 (0%)	1 of 16 (6.3%)	0 of 16
Cohort 1 Low Temperature : Pindolol	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Cohort 1 High Temperature : Placebo	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Cohort 1 High Temperature : Proprannolol	0 of 16 (0%)	1 of 16 (6.3%)	0 of 16
Cohort 1 High Temperature : Dantrolene	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Cohort 1 High Temperature : Magnesium	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Cohort 1 High Temperature : Pindolol	0 of 16 (0%)	1 of 16 (6.3%)	0 of 16
Cohort 2 : Placebo	0 of 18 (0%)	0 of 18 (0%)	0 of 18
Cohort 2 : Caffeine	0 of 18 (0%)	0 of 18 (0%)	0 of 18
Cohort 2 : Naltrexone	0 of 18 (0%)	5 of 18 (27.8%)	0 of 18
Cohort 2 : Qsymia	0 of 18 (0%)	2 of 18 (11.1%)	0 of 18
Cohort 2 : Topiramate	0 of 18 (0%)	5 of 18 (27.8%)	0 of 18
Cohort 2 : Phentermine	0 of 18 (0%)	2 of 18 (11.1%)	0 of 18
Cohort 3 : Placebo	0 of 13 (0%)	1 of 13 (7.7%)	0 of 13
Cohort 3 : Mirabegron 50mg	0 of 13 (0%)	1 of 13 (7.7%)	0 of 13
Cohort 3 : Mirabegron 200mg	0 of 13 (0%)	1 of 13 (7.7%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21177944Cannon B, Nedergaard J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol. 2011 Jan 15;214(Pt 2):242-53. doi: 10.1242/jeb.050989.
Background: PubMed 21490370van Marken Lichtenbelt WD, Schrauwen P. Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol. 2011 Aug;301(2):R285-96. doi: 10.1152/ajpregu.00652.2010. Epub 2011 Apr 13.
Background: PubMed 17473055Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52. doi: 10.1152/ajpendo.00691.2006. Epub 2007 May 1.
Derived from this study: PubMed 29980535Baskin AS, Linderman JD, Brychta RJ, McGehee S, Anflick-Chames E, Cero C, Johnson JW, O'Mara AE, Fletcher LA, Leitner BP, Duckworth CJ, Huang S, Cai H, Garraffo HM, Millo CM, Dieckmann W, Tolstikov V, Chen EY, Gao F, Narain NR, Kiebish MA, Walter PJ, Herscovitch P, Chen KY, Cypess AM. Regulation of Human Adipose Tissue Activation, Gallbladder Size, and Bile Acid Metabolism by a beta3-Adrenergic Receptor Agonist. Diabetes. 2018 Oct;67(10):2113-2125. doi: 10.2337/db18-0462. Epub 2018 Jul 6.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: Yes. .All IPD that underlie results in a publication

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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.

Kong Y Chen, Ph.D. principal investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 24 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 16 Oct 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

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 16 Oct 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?

Resting Energy Expenditure at Low Temperature (time frame: Cohort 1: Days 1-17). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01950520, which also lists 4 linked publications.

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 16 Oct 2024.