Cold-induced Brown Fat Activation and Hepatic Steatosis

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Other: Cold exposure

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Florian Kiefer, MD, PhD; Phone Number: 43120 +43140400; Email: florian.kiefer@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Florian Kiefer, MD, PhD; Phone Number: 43120 +43140400; Email: florian.kiefer@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cold exposure	Other: Cold exposure; Two hours of mild cold exposure using a water-perfused vest
No Intervention: Room temperature

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic lipid content (%)	Magnetic resonance imaging-proton density fat fraction	Six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brown adipose tissue volume (ml) / activity (SUVmean)	18-fluorodeoxyglucose positron emission tomography/ magnetic resonance imaging	Six weeks
Basal metabolic rate (kcal/day/kg fat-free body mass)	Indirect calorimetry	Six weeks
Cold-induced non-shivering thermogenesis (%)	Indirect calorimetry: percentage increase in basal metabolic rate before and after cold exposure	Six weeks
Body fat mass (kg)	Air displacement plethysmography	Six weeks
Insulin sensitivity	"Matsuda Index" for 2 hour standard oral glucose tolerance test	Six weeks

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Florian Kiefer, MD, PhD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 18, 2019
• First Submitted That Met QC Criteria: January 18, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 1911/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No