Obesity
Conditions
Keywords
obesity, tirzepatide, brown adipose tissue, beige adipose tissue, adipose tissue browning, energy expenditure
Brief summary
This study is testing whether a new anti-obesity medicine called tirzepatide can increase the activity of special fat cells in the body that help burn energy. These fat cells are known as brown and beige fat. The study includes women with obesity and will last 24 weeks. Participants will receive either tirzepatide or a placebo (a look-alike injection with no active drug). Researchers will measure the amount and activity of brown fat using medical imaging (PET/CT, MRI, and thermal camera), and examine fat tissue samples to look for changes in gene activity and structure that show beige fat activation. The study will also evaluate how these fat changes affect body weight, energy use, hormone levels, blood sugar, and other health markers. The goal is to learn whether tirzepatide helps improve metabolism by increasing energy-burning fat in addition to reducing appetite.
Interventions
DRUGTirzepatide
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. It will be administered via subcutaneous injection once weekly in a dose-titration scheme: starting at 2.5 mg, and increased every 4 weeks by 2.5 mg up to a maximum of 15 mg, based on tolerability. The medication will be supplied in prefilled pens identical in appearance to placebo pens.
DRUGPlacebo
Placebo will be administered via subcutaneous injection once weekly using pens that are visually indistinguishable from those used for tirzepatide. Dose escalation will follow the same schedule (2.5 mg-equivalent increments every 4 weeks) to preserve blinding integrity.
Sponsors
University Medical Centre Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Female sex * Age between 18 and 50 years * BMI between 30 kg/m² and 40 kg/m² at pre-screening * Prior comprehensive non-pharmacological and non-surgical management of obesity, including a history of at least 12 months of intensive lifestyle intervention with a maximum weight reduction of less than 5% * Stable body weight within the three months preceding study enrollment (defined as weight fluctuations within 5%) * No prior pharmacological or surgical interventions for obesity * Euthyroid state * Eumenorrhea or Oligomenorrhea * Ability to comprehend the study objectives and procedures * Willingness to provide informed consent and to comply with the study protocol, including the use of highly effective contraception during the study period, with signed consent and agreement provided in duplicate * Commitment to use highly reliable contraception and absence of plans for pregnancy within the 8 months following enrollment
Exclusion criteria
* Pregnancy or lactation * Postmenopausal * Amenorea * Type 2 diabetes * Reliance on natural contraception methods * Non-compliance with previous therapeutic regimens * Personal history of malignancy * Personal or family history of medullary thyroid carcinoma * Personal history of pancreatitis * Personal history of cholelithiasis * Personal history of major depressive episodes or suicidal ideation * Personal history of acute coronary events or hemodynamically significant coronary artery disease * Psychiatric disorders * Current treatment with sympathomimetics or sympatholytics * Excessive alcohol consumption
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brown Adipose Tissue Activity and Volume | Baseline to Week 24 | Assessed using 18F-FDG-PET/CT, magnetic resonance imaging (MRI), and infrared thermography. Outcome measured as change in mean standardized uptake value, supraclavicular skin temperature, and BAT volume in predefined anatomical regions (supraclavicular and cervical areas) between baseline and after 24 weeks of treatment. |
| Change in Molecular Markers of Browning in Subcutaneous White Adipose Tissue | Baseline to Week 24 | Measured as changes in the expression levels of uncoupling protein 1 (UCP1) and other browning-associated genes (via RT-PCR and RNA sequencing) in subcutaneous white adipose tissue (WAT) biopsies. Additionally, assessed through histomorphometric analysis of adipocyte phenotype, including the proportion of multilocular (plurivacuolar) adipocytes, immune cell infiltration, and microvascular density, to characterize tissue remodeling indicative of beige adipocyte induction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Different BAT Assessment Methods | Baseline and Week 24 | Comparative analysis between 18F-FDG-PET/CT, MRI fat fraction, and infrared thermography for assessing BAT activity and volume. |
| Change in Resting Energy Expenditure | Baseline to Week 24 | Measured by indirect calorimetry using a portable metabolic analyzer. Outcome reported as absolute change in REE (kcal/day). |
| Association Between Changes in Resting Energy Expenditure, Metabolic Health Markers, and Thermogenic Adipose Tissue | Baseline to Week 24 | Assessed by evaluating correlations between changes in resting energy expenditure (REE, measured by indirect calorimetry), metabolic health parameters (including glucose metabolism, insulin sensitivity indices, lipid profile, and hormonal markers), body composition changes, and alterations in thermogenic adipose tissue activity and volume (as measured by 18F-FDG-PET/CT, MRI, and thermography). This outcome aims to determine the interrelationship between metabolic adaptations and thermogenic fat activation following tirzepatide treatment. |
| Association Between Resting Energy Expenditure, Metabolic Health Markers, and Thermogenic Adipose Tissue | Baseline | Assessed by evaluating correlations between anthropometric data, resting energy expenditure (REE, measured by indirect calorimetry), metabolic health parameters (including glucose metabolism, insulin sensitivity indices, lipid profile, and hormonal markers), body composition, and thermogenic adipose tissue activity and volume (as measured by 18F-FDG-PET/CT, MRI, and thermography). This outcome aims to determine variables that correlate with pre-treatment thermogenic adipose tissue quantity and activity. |
Countries
Slovenia
Outcome results
None listed