Cold-induced Brown Fat Activation and Hepatic Steatosis
Primary Purpose
Non-Alcoholic Fatty Liver Disease
Status
Suspended
Phase
Not Applicable
Locations
Austria
Study Type
Interventional
Intervention
Cold exposure
Sponsored by
About this trial
This is an interventional basic science trial for Non-Alcoholic Fatty Liver Disease
Eligibility Criteria
Inclusion Criteria:
- body mass index 28 - 40 kg/m^2
- hepatic lipid content > 10 %
Exclusion Criteria:
- endocrine disease, except treated hypo-/hyperthyroidism and hypertriglyceridemia (<500 mg/dl) and untreated type II diabetes mellitus (fasting glucose < 140 mg/dl)
- use of beta-blockers, alpha-blockers and rilmenidine
- chronic kidney disease
- inflammatory bowel disease
- active malignant disease
- autoimmune disease
- chronic alcohol abuse or alcohol consumption greater than 30g/d for men or 20 g/d for women
- transferrin saturation > 40%
- serum alpha-1 antitrypsin < 90 mg/dl
- serum ceruloplasmin < 20 mg/dl
- positive serology for autoimmune hepatitis
- positive hepatitis serology
- liver cirrhosis
- portal hypertension
- pregnancy
- contraindications for magnetic resonance imaging
Sites / Locations
- Medical University of Vienna
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Cold exposure
Room temperature
Arm Description
Outcomes
Primary Outcome Measures
Hepatic lipid content (%)
Magnetic resonance imaging-proton density fat fraction
Secondary Outcome Measures
Brown adipose tissue volume (ml) / activity (SUVmean)
18-fluorodeoxyglucose positron emission tomography/ magnetic resonance imaging
Basal metabolic rate (kcal/day/kg fat-free body mass)
Indirect calorimetry
Cold-induced non-shivering thermogenesis (%)
Indirect calorimetry: percentage increase in basal metabolic rate before and after cold exposure
Body fat mass (kg)
Air displacement plethysmography
Insulin sensitivity
"Matsuda Index" for 2 hour standard oral glucose tolerance test
Full Information
NCT ID
NCT03811236
First Posted
January 18, 2019
Last Updated
April 5, 2022
Sponsor
Medical University of Vienna
1. Study Identification
Unique Protocol Identification Number
NCT03811236
Brief Title
Cold-induced Brown Fat Activation and Hepatic Steatosis
Official Title
Cold-induced Brown Fat Activation and Hepatic Steatosis
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Suspended
Why Stopped
due to the COVID pandemic
Study Start Date
January 21, 2019 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
In the recent years, research on brown adipose tissue (BAT) revealed that larger amounts as well as higher activity thereof are associated with a favourable metabolic phenotype. Longitudinal studies which applied recurrent cooling sessions demonstrated a high plasticity of BAT which significantly increased in size and activity during these studies. These changes were accompanied by improvements in body fat mass as well as insulin sensitivity. Non-alcoholic fatty liver disease (NAFLD) is estimated to advance to the primary cause of liver cirrhosis and hepatocellular carcinoma in the following years. Besides predisposing genetic and possibly nutritional factors, the insulin resistance syndrome and obesity are the main factors contributing to this excessive hepatic lipid accumulation.
The aim of this study is to investigate whether BAT recruitment via cold-acclimation results in decreased hepatic lipid content in overweight/obese patients with NAFLD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Fatty Liver Disease
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
26 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cold exposure
Arm Type
Experimental
Arm Title
Room temperature
Arm Type
No Intervention
Intervention Type
Other
Intervention Name(s)
Cold exposure
Intervention Description
Two hours of mild cold exposure using a water-perfused vest
Primary Outcome Measure Information:
Title
Hepatic lipid content (%)
Description
Magnetic resonance imaging-proton density fat fraction
Time Frame
Six weeks
Secondary Outcome Measure Information:
Title
Brown adipose tissue volume (ml) / activity (SUVmean)
Description
18-fluorodeoxyglucose positron emission tomography/ magnetic resonance imaging
Time Frame
Six weeks
Title
Basal metabolic rate (kcal/day/kg fat-free body mass)
Description
Indirect calorimetry
Time Frame
Six weeks
Title
Cold-induced non-shivering thermogenesis (%)
Description
Indirect calorimetry: percentage increase in basal metabolic rate before and after cold exposure
Time Frame
Six weeks
Title
Body fat mass (kg)
Description
Air displacement plethysmography
Time Frame
Six weeks
Title
Insulin sensitivity
Description
"Matsuda Index" for 2 hour standard oral glucose tolerance test
Time Frame
Six weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
body mass index 28 - 40 kg/m^2
hepatic lipid content > 10 %
Exclusion Criteria:
endocrine disease, except treated hypo-/hyperthyroidism and hypertriglyceridemia (<500 mg/dl) and untreated type II diabetes mellitus (fasting glucose < 140 mg/dl)
use of beta-blockers, alpha-blockers and rilmenidine
chronic kidney disease
inflammatory bowel disease
active malignant disease
autoimmune disease
chronic alcohol abuse or alcohol consumption greater than 30g/d for men or 20 g/d for women
transferrin saturation > 40%
serum alpha-1 antitrypsin < 90 mg/dl
serum ceruloplasmin < 20 mg/dl
positive serology for autoimmune hepatitis
positive hepatitis serology
liver cirrhosis
portal hypertension
pregnancy
contraindications for magnetic resonance imaging
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Florian Kiefer, MD, PhD
Organizational Affiliation
Medical University of Vienna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
12. IPD Sharing Statement
Plan to Share IPD
No
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Cold-induced Brown Fat Activation and Hepatic Steatosis
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