Clinical trial NCT04614116: Cold Induced Futile Cycles In White Adipose Tissue
Official title: Cold Induced Futile Cycles In White Adipose Tissue: Quantification And Characterization With Dual Glucose Analysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolism Disorder
Keywords: Glucose metablism
futil cycles
FDG PET/CT
Lead sponsor: Kantonsspital Baden
Sponsor class: OTHER
First posted: 2020-11-03
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non blinded, randomised, open label
Primary purpose: BASIC_SCIENCE

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of FDG influx into WAT
timeFrame: 2 days
Secondary outcomes:
measure: Quantification of 13C-Glucose metabolites in fat
timeFrame: 2 days
measure: Quantification of 13C-Glucose metabolites in blood
timeFrame: 2 days
Other outcomes:
Locations:
city: Baden
country: Switzerland
facility: Kantonsspitla Baden
state: Aargau
Study officials:
affiliation: Kantonsspital Baden
name: Irene A. Burger, MD
role: PRINCIPAL_INVESTIGATOR
References: