Effect of Tirzepatide on Brown Adipose Tissue in Obesity

NCT06893211 | Active Not Recruiting Phase 2

• 1 other identifier: 0120-56/2024-2711-7
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Keywords

obesity; tirzepatide; brown adipose tissue; beige adipose tissue; adipose tissue browning; energy expenditure

Outcome Measures

Primary Outcomes (2)

• Change in Brown Adipose Tissue Activity and Volume

  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.

  Baseline to Week 24

• Change in Molecular Markers of Browning in Subcutaneous White Adipose Tissue

  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.

  Baseline to Week 24

Secondary Outcomes (4)

• Correlation Between Different BAT Assessment Methods

  Baseline and Week 24

• Change in Resting Energy Expenditure

  Baseline to Week 24

• Association Between Changes in Resting Energy Expenditure, Metabolic Health Markers, and Thermogenic Adipose Tissue

  Baseline to Week 24

• Association Between Resting Energy Expenditure, Metabolic Health Markers, and Thermogenic Adipose Tissue

  Baseline

Study Arms (2)

Tirzepatide

EXPERIMENTAL

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tirzepatide DRUG

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.

Tirzepatide

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (1)

• Herman R, Jensterle M, Horvat S, Lezaic L, Snoj Z, Pusnik I, Goricar K, Cor A, Pusnik L, Mlacnik V, Hanzelic L, Janez A. Effect of tirzepatide-induced weight loss on adipose tissue in obesity: rationale and design of the randomized placebo-controlled Tirzepatide Brown and Beige Adipose Tissue Activation (TABFAT) trial. Trials. 2025 Aug 22;26(1):300. doi: 10.1186/s13063-025-09045-9.

  PMID: 40847412 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 25, 2025
• Study Start: March 18, 2025
• Primary Completion: November 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

SL (1)