Cold Induced Futile Cycles In White Adipose Tissue (Metabol)

Cold Induced Futile Cycles In White Adipose Tissue: Quantification And Characterization With Dual Glucose Analysis

Investigation of futile cycles in white adipose tissue under cold conditions for thermogenesis using two substitutes for glucose metabolism (18F-FDG and 13C-Glucose).

Study Overview

• Status: Completed
• Conditions: Metabolism Disorder
• Intervention / Treatment: Diagnostic test: FDG PET/CT; Diagnostic test: 13C-Glucose injection; Other: External cooling

Detailed Description

Thermogenesis is defined as a process, which generates heat by the depletion of energy-rich molecules. Evolutionary, it is an essential process that allows the survival at lower temperatures. Since the discovery of brown adipose tissue (BAT) it is believed that this part of the adipose tissue can dissipate energy for heat thanks to the uncoupling protein 1 (UCP1). Since energy expenditure is increased as a consequence of thermogenesis, pharmacological induction of this pathway presents an interesting therapeutic target to counter obesity. However, recent investigations indicate that white adipose tissue (WAT) is much more versatile and probably essentially indispensable for thermogenesis.

To investigate the mechanism of this futile cycle in WAT we plan to investigate the glucose metabolism in 24 healthy volunteers with 2 exams (one with and one without external cooling) with two substitutes for glucose. We will use 18F-FDG to quantify the glucose influx into WAT using dynamic PET/CT scans and 13C-Glucose to analyze the downstream metabolites.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Aargau
    • Baden, Aargau, Switzerland, 5404
      • Kantonsspitla Baden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Informed Consent as documented by signature
• Healthy participants, as determined by screening assessments and Principal Investigator's judgment
• Health status is defined by the absence of evidence of any active or chronic disease following a medical and surgical history, basic physical examination and blood test

Exclusion Criteria:

• any clinically relevant history or the presence of e.g. respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, metabolic disease, etc.
• Intake of the following medications: Insulin, oral antidiabetic drugs, GLP-1-agonists, Corticosteroids, Sympathomimetic and Sympatholytic drug, Beta-Blocker, Statins.
• BMI > 35 kg/m2
• Resting pulse rate > 70 bpm, resting blood pressure > 130/90 mmHg.
• Serum creatinine > 145 µmol/L
• ASAT> 75 U/L and ALAT > 75 U/L
• γ GT > 100 UI/L and total bilirubin > 30 µmol/l
• Glucose > 7.1 mmol/L
• HbA1c > 46 mmol/mol (>6.4%)
• Intake of anticoagulants or inhibitors of platelet aggregation (e.g. Aspirin, clopidogrel).
• Known tendency to form keloids (hypertrophic scar tissue)
• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present study
• Participation in another study involving ionizing radiation in the same year
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Biopsy without cold induction; Participants will undergo a fat biopsy after the first scan, without cooling	Diagnostic test: FDG PET/CT; o 75 MBq 18F-FDG will be injected through the intravenous line on the scanner manually (bolus injection) with a simultaneous start of dynamic FDG-PET/CT scan for 45 minutes and a partial body scan from head to the abdomen after 45 minutes. Total scan time 60 minutes.; Diagnostic test: 13C-Glucose injection; 0.5 g 13C-Glucose i.v. infusion over 5 minutes, after termination of FDG injection
Other: Biopsy with cold induction; Participants will undergo a fat biopsy after the second scan, with cooling	Diagnostic test: FDG PET/CT; o 75 MBq 18F-FDG will be injected through the intravenous line on the scanner manually (bolus injection) with a simultaneous start of dynamic FDG-PET/CT scan for 45 minutes and a partial body scan from head to the abdomen after 45 minutes. Total scan time 60 minutes.; Diagnostic test: 13C-Glucose injection; 0.5 g 13C-Glucose i.v. infusion over 5 minutes, after termination of FDG injection; Other: External cooling; water-circulating cooling/warming sleeves connected to a medical cooling device (Hilotherm Clinic®, Hilotherm GmbH, Germany) will be placed around the subject's abdomen and lower back. Initially the temperature of the water will be set to 25°C. A mild cold stimulus will be applied by reducing the temperature of the circulating water by approximately 1°C every 2 minutes to a minimum of 10°C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of FDG influx into WAT	Comparing the 18F-FDG influx rate (Ki) into the white adipose tissue with and without cold stimulation (intra-individually).	2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of 13C-Glucose metabolites in fat	Comparing the 13C-Glucose accumulation in white adipose tissue between Group A (without cold) and B (with cold) stimulation	2 days
Quantification of 13C-Glucose metabolites in blood	13C-Lactate concentration in blood samples between Group A (without cold) and B (with cold) stimulation.	2 days

Collaborators and Investigators

• Sponsor: Kantonsspital Baden
• Investigators: Principal Investigator: Irene A. Burger, MD, Kantonsspital Baden

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Actual): February 17, 2022
• Study Completion (Actual): March 29, 2022

Study Registration Dates

• First Submitted: October 28, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): November 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: FDG PET/CT; Glucose metablism; futil cycles
• Additional Relevant MeSH Terms: Metabolic Diseases
• Other Study ID Numbers: Cold exposure of WAT

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