Investigating Brown Adipose Tissue Activation in Humans

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT01935791
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arms: 9
• Duration (Months): 64.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine what can activate brown adipose tissue (BAT).

Condition or Disease	Intervention/Treatment	Phase
Metabolic Diseases	Other: Period 1 Visit 1 - Cold PET-CT Vehicle, Visit 2 -Warm PET-CT Vehicle; Drug: Period 1 Visit 1 - Cold PET-CT Vehicle, Visit 2 -Warm PET-CT Glucagon; Other: Period 1 Visit 1 - Cold PET-CT Vehicle, no visit 2 as BAT negative; Drug: Period 2 - Visit 1 Warm Control vehicle, Visit 2 Warm Glucagon, Visit 3 Cold control; Drug: Period 2 - Visit 1 Warm Glucagon, Visit 2 Cold control , Visit 3 Warm control; Drug: Period 2 -Visit 1 cold control, Visit 2 warm control, Visit 3 Warm glucagon; Drug: Period 2 -Visit 1 cold control, visit 2 warm glucagon, visit 3 warm control; Drug: Period 2- Visit 1 Warm glucagon, visit 2 warm control, visit 3 cold control; Drug: Period 2 - Visit 1 Warm control, visit 2 cold control, visit 3 warm glucagon	N/A

Detailed Description

We will investigate different stimuli (i.e. hormones) to determine which can stimulate BAT.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Investigating Brown Adipose Tissue Activation in Humans
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Nov 5, 2018
• Actual Study Completion Date: Nov 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Period 1 Visit 1 - Cold PET-CT Vehicle, Visit 2 -Warm PET-CT Vehicle Visit 1. Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst wearing a cooling vest and receiving an infusion of gelofusine. Visit 2 Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst receiving an infusion of gelofusine without a cooling vest.	Other: Period 1 Visit 1 - Cold PET-CT Vehicle, Visit 2 -Warm PET-CT Vehicle; Temperature
Experimental: Period 1 Visit 1 - Cold PET-CT Vehicle, Visit 2 -Warm PET-CT Glucagon Visit 1. Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst wearing a cooling vest and receiving an infusion of gelofusine Visit 2 Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min without a cooling vest.	Drug: Period 1 Visit 1 - Cold PET-CT Vehicle, Visit 2 -Warm PET-CT Glucagon; Hormone
Active Comparator: Period 1 Visit 1 - Cold PET-CT Vehicle, no visit 2 as BAT negative Visit 1. Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst wearing a cooling vest and receiving an infusion of gelofusine. No brown adipose tissue (BAT) identified on visit 1, therefore no visit 2.	Other: Period 1 Visit 1 - Cold PET-CT Vehicle, no visit 2 as BAT negative; Temperature
Experimental: Period 2 - Visit 1 Warm Control vehicle, Visit 2 Warm Glucagon, Visit 3 Cold control Visit 1- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees celsius. Visit 2 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees celsius. Visit 3 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest.	Drug: Period 2 - Visit 1 Warm Control vehicle, Visit 2 Warm Glucagon, Visit 3 Cold control; Hormone
Experimental: Period 2 - Visit 1 Warm Glucagon, Visit 2 Cold control , Visit 3 Warm control Visit 1- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees celsius. Visit 2 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest. Visit 3 Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees celsius.	Drug: Period 2 - Visit 1 Warm Glucagon, Visit 2 Cold control , Visit 3 Warm control; Hormone
Experimental: Period 2 -Visit 1 cold control, Visit 2 warm control, Visit 3 Warm glucagon Visit 1 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest. Visit 2 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees celsius. Visit 3 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees celsius.	Drug: Period 2 -Visit 1 cold control, Visit 2 warm control, Visit 3 Warm glucagon; hormone
Experimental: Period 2 -Visit 1 cold control, visit 2 warm glucagon, visit 3 warm control Visit 1 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest. Visit 2- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees Celsius. Visit 3 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees Celsius.	Drug: Period 2 -Visit 1 cold control, visit 2 warm glucagon, visit 3 warm control; hormone
Experimental: Period 2- Visit 1 Warm glucagon, visit 2 warm control, visit 3 cold control Visit 1- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees Celsius. Visit 2 Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees Celsius. Visit 3- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest.	Drug: Period 2- Visit 1 Warm glucagon, visit 2 warm control, visit 3 cold control; hormone
Experimental: Period 2 - Visit 1 Warm control, visit 2 cold control, visit 3 warm glucagon Visit 1 Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees Celsius. Visit 2- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest. Visit 3 Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees Celsius	Drug: Period 2 - Visit 1 Warm control, visit 2 cold control, visit 3 warm glucagon; Hormone

Outcome Measures

Primary Outcome Measures

1. Brown Adipose Tissue Activation Following Glucagon or Saline Infusion [2hours]

   Period 1 Brown Adipose Tissue (BAT) activation measured using metabolic rate of glucose (MR[gluc]) during F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET-CT) for Cold PET-CT Vehicle vs Warm PET-CT Vehicle vs warm PET-CT Glucagon.

2. Increase in Energy Expenditure Following Glucagon or Saline Infusion [2hours]

   Period 2 Increase in energy expenditure measured using indirect calorimetry for Cold control vs Warm Control vs Warm Glucagon.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• aged >18 years

Exclusion Criteria:

• medical conditions

• recreational drug use

• participation in other trials within the preceding 2 months

• blood donation within 3 months of study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imperial College London	London		United Kingdom

Sponsors and Collaborators

• Imperial College London

Investigators

• Principal Investigator: Waljit Dhillo, Imperial College London

Study Documents (Full-Text)

• Study Protocol - May 29, 2014
• Statistical Analysis Plan - May 29, 2014

More Information

Additional Information:

• Glucagon increases energy expenditure independently of brown adipose tissue activation in humans.
• Thermal Imaging Is a Noninvasive Alternative to PET/CT for Measurement of Brown Adipose Tissue Activity in Humans

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT01935791
• Other Study ID Numbers: 13HH0688
• First Posted: Sep 5, 2013
• Last Update Posted: May 18, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: Metabolic Diseases
• Additional relevant MeSH terms: Metabolic Diseases; Glucagon; Glucagon-Like Peptide 1

Study Results

Participant Flow

Arm/Group Title	Period 1 Visit 1 - Cold PET-CT Vehicle, Visit 2 -Warm PET-CT Vehicle	Period 1 Visit 1 - Cold PET-CT Vehicle, Visit 2 -Warm PET-CT Glucagon	Period 1 Visit 1 - Cold PET-CT Vehicle, no Visit 2 as BAT Negative	Period 2 - Visit 1 Warm Control Vehicle, Visit 2 Warm Glucagon, Visit 3 Cold Control	Period 2 - Visit 1 Warm Glucagon, Visit 2 Cold Control , Visit 3 Warm Control	Period 2 -Visit 1 Cold Control, Visit 2 Warm Control, Visit 3 Warm Glucagon	Period 2 -Visit 1 Cold Control, Visit 2 Warm Glucagon, Visit 3 Warm Control	Period 2- Visit 1 Warm Glucagon, Visit 2 Warm Control, Visit 3 Cold Control	Period 2 -Visit 1 Warm Control, Visit 2 Cold Control, Visit 3 Warm Glucagon
Arm/Group Description	Visit 1. Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst wearing a cooling vest and receiving an infusion of gelofusine. Visit 2 Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst receiving an infusion of gelofusine without a cooling vest.	Visit 1. Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst wearing a cooling vest and receiving an infusion of gelofusine Visit 2 Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min without a cooling vest.	Visit 1. Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst wearing a cooling vest and receiving an infusion of gelofusine. No brown adipose tissue (BAT) identified on visit 1, therefore no visit 2.	Visit 1- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees celsius. Visit 2 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees celsius. Visit 3 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest.	Visit 1- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees celsius. Visit 2 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest. Visit 3 Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees celsius.	Visit 1 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest. Visit 2 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees celsius. Visit 3 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees celsius.	Visit 1 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest. Visit 2- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees Celsius. Visit 3 - Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees Celsius.	Visit 1- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees Celsius. Visit 2 Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees Celsius. Visit 3- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest.	Visit 1 Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees Celsius. Visit 2- Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest. Visit 3 Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees Celsius
Period Title: Period 1
STARTED	4	4	3	0	0	0	0	0	0
COMPLETED	4	4	3	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Period 1
STARTED	0	0	0	2	3	1	1	3	1
COMPLETED	0	0	0	2	3	1	1	3	1
NOT COMPLETED	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants who were randomised
Overall Participants	11
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	26
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	11 100%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United Kingdom	11 100%
BMI (kg/m2) [Mean (Full Range) ]
Mean (Full Range) [kg/m2]	22.5

Outcome Measures

1. Primary Outcome

Title	Brown Adipose Tissue Activation Following Glucagon or Saline Infusion
Description	Period 1 Brown Adipose Tissue (BAT) activation measured using metabolic rate of glucose (MR[gluc]) during F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET-CT) for Cold PET-CT Vehicle vs Warm PET-CT Vehicle vs warm PET-CT Glucagon.
Time Frame	2hours

Outcome Measure Data

Analysis Population Description

Period 1 Parallel design (3 out of 11 participants did not have BAT activation and therefore they were not included in the analysis). Period 2 Crossover design

Arm/Group Title	Period 1 Cold PET-CT Vehicle	Period 1 Warm PET-CT Vehicle	Period 1 Warm PET(CT) Glucagon
Arm/Group Description	Visit 1. emission tomography, computerised tomography-(PET)CT, whilst wearing a cooling vest and receiving an infusion of gelofusine.	Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst receiving an infusion of gelofusine without a cooling vest.	Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min without a cooling vest.
Measure Participants	8	4	4
Mean (Standard Deviation) [MR[gluc] umol/kg/min]	0.074 (0.007)	0.010 (0.003)	0.029 (0.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Period 1 Cold PET-CT Vehicle, Period 1 Warm PET-CT Vehicle, Period 1 Warm PET(CT) Glucagon
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments	The p-values were adjusted for multiple comparisons. The a priori threshold for statistical significance is p<0.05.
	Method	ANOVA
	Comments	plus Tukey test

2. Primary Outcome

Title	Increase in Energy Expenditure Following Glucagon or Saline Infusion
Description	Period 2 Increase in energy expenditure measured using indirect calorimetry for Cold control vs Warm Control vs Warm Glucagon.
Time Frame	2hours

Outcome Measure Data

Analysis Population Description

Period 2 Crossover design

Arm/Group Title	Period 2 - Cold Control	Period 2 - Warm Control	Period 2 -Warm Glucagon
Arm/Group Description	Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest.	Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees celsius.	Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees celsius.
Measure Participants	11	11	11
Mean (Standard Deviation) [increase in energy expenditure kcal/day]	193.0 (27.2)	41.1 (70)	230.8 (30.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Period 1 Cold PET-CT Vehicle, Period 1 Warm PET-CT Vehicle, Period 1 Warm PET(CT) Glucagon
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	plus Tukey test

Adverse Events

Time Frame	3 years
Adverse Event Reporting Description	Patients were monitored for adverse events throughout each visit and had the contact details of the main investigator for any issues in between visits.
Arm/Group Title	Period 1 Visit 1 Cold Vehicle		Period 1 Visit 2 Warm Glucagon		Period 1 Visit 2 Warm Vehicle		Period 2 Cold Control		Period 2 Warm Control		Period 2 Warm Glucagon
Arm/Group Description	Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst wearing a cooling vest and receiving an infusion of gelofusine.		Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min without a cooling vest.		Participants underwent F-fluorodeoxyglucose (18F-FDG) positron emission tomography, computerised tomography-(PET)CT, whilst receiving an infusion of gelofusine without a cooling vest.		Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine and wearing a cooling vest.		Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of gelofusine. They were situated in an ambient temperature of 22-25 degrees celsius.		Each participant had calorimetry testing and thermal imaging whilst receiving an infusion of Glucagon at a dose of 50ng/kg/min. They were situated in an ambient temperature of 22-25 degrees celsius.
All Cause Mortality
	Period 1 Visit 1 Cold Vehicle		Period 1 Visit 2 Warm Glucagon		Period 1 Visit 2 Warm Vehicle		Period 2 Cold Control		Period 2 Warm Control		Period 2 Warm Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/4 (0%)		0/4 (0%)		0/11 (0%)		0/11 (0%)		0/11 (0%)
Serious Adverse Events
	Period 1 Visit 1 Cold Vehicle		Period 1 Visit 2 Warm Glucagon		Period 1 Visit 2 Warm Vehicle		Period 2 Cold Control		Period 2 Warm Control		Period 2 Warm Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/4 (0%)		0/4 (0%)		0/11 (0%)		0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Period 1 Visit 1 Cold Vehicle		Period 1 Visit 2 Warm Glucagon		Period 1 Visit 2 Warm Vehicle		Period 2 Cold Control		Period 2 Warm Control		Period 2 Warm Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/4 (0%)		0/4 (0%)		0/11 (0%)		0/11 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.