Response to Semaglutide in Non-diabetic Obese Patients With Varying Degrees of Insulin Resistance (TRIM-IR)
Treatment Response to Incretin Mimetics in Non-diabetic Obese Patients With and Without Insulin Resistance (TRIM-IR)
Incretin mimetics are widely used pharmacological treatments for weight loss, known for their high efficacy and favorable safety profile. As the most commonly prescribed drug in this class, semaglutide is effective in both diabetic and non-diabetic individuals. However, treatment responses vary significantly, with non-diabetic individuals typically experiencing better weight loss outcomes. Despite this, up to 10% of non-diabetic individuals show little or no response to treatment, and the reasons for this variability remain unclear.
The TRIM-IR study aims to investigate the role of insulin resistance (IR) in weight loss outcomes among non-diabetic obese individuals receiving semaglutide. This single-center, observational study will assess the impact of IR on weight loss, body composition, and adipose tissue function during the first 16 weeks of semaglutide therapy. The study will also explore molecular markers of adipose tissue dysfunction, focusing on the transition from dysfunctional to healthy adipose tissue.
The investigators hypothesize, that individuals with lower IR will experience greater weight loss than those with higher IR, and that the glucose infusion rate (GIR) during hyperinsulinemic euglycemic clamp testing will correlate with weight loss variability. Secondary objectives include comparing changes in fat and lean mass, reductions in visceral fat, and improvements in adipose tissue function before and after 16 weeks of treatment. Exploratory analyses will assess adipocyte subpopulations and their response to insulin sensitivity changes.
A total of 40 participants, equally distributed by gender, will be enrolled to ensure statistical power for detecting clinically relevant differences. The study aims to optimize semaglutide use for personalized obesity treatment and provide insights into the relationship between obesity, insulin resistance, and adipose tissue plasticity, with implications for improving obesity management and cardiovascular health outcomes.
Przegląd badań
Status
Typ studiów
Zapisy (Rzeczywisty)
Kontakty i lokalizacje
Lokalizacje studiów
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Canton of Aargau
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Aarau, Canton of Aargau, Szwajcaria, 5001
- Cantonal Hospital Aarau
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Metoda próbkowania
Badana populacja
The investigators plan to include a total of 40 non-diabetic, obese individuals that will undergo treatment with semaglutide as a weight-loss intervention independent of our observational study. To avoid a highly heterogeneous participant group, inclusion in the study will be limited to individuals with a BMI between 30 and 40 kg/m². Patients with a prediabetic state will not be excluded.
Opis
Inclusion Criteria:
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Age between 18 and 60 years
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BMI 30 - 40 kg/m2
a. Participants must meet the eligibility criteria for coverage under the KVG (Federal Health Insurance Act) and the Specialties List, which include a weight-related comorbidity (arterial hypertension, dyslipidemia) for participants with a BMI of 30- 35 kg/m2
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Planned therapy with semaglutide as a weight loss intervention
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No known presence of a diabetic state
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Ability to understand and sign a Patient Information and Consent Form
Exclusion Criteria:
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Pregnancy or active breast feeding
- Therapy with semaglutide is not approved for use during pregnancy or while breastfeeding, as its safety and efficacy in these conditions have not been established.
- Pregnancy is an exclusion criterion for the planned investigations to avoid placing pregnant individuals under unnecessary physical or psychological stress that could pose risks to both the individual and the fetus.
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Medication and/or pathologies that prevent the safe execution of the fat tissue biopsies (e.g. allergy towards local anesthetics, disorders of coagulation, treatment with anticoagulants)
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Medical conditions that prevent examinations and testing (e.g. epilepsia, symptomatic cardiovascular disease)
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History of or planned bariatric surgery
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HbA1c ≥ 6.5% as measured by the central laboratory at screening
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Fasting plasma-glucose >7.0 mmol/l
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History of type 1 or type 2 diabetes mellitus
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Treatment with glucose-lowering agent(s) (e.g. Metformin) within 90 days before screening
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Treatment with a GLP-1 (glucagon like peptide 1) receptor agonist within 180 days before screening
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A self-reported change in body weight >5% within 90 days before screening
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Active malignancy (<2a since remission)
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Treatment with any medication for the indication of obesity within the past 90 days before screening
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Uncontrolled thyroid disease, defined as thyroid stimulating hormone (TSH) > 10 mIU/L or < 0.4 mIU/L as measured by the central laboratory at screening
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Modele obserwacyjne: CASE_ONLY
- Perspektywy czasowe: PROSPECTIVE
Kohorty i interwencje
Grupa / Kohorta |
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Non-diabetic obese individuals on semaglutide for weight loss
Non-diabetic obese individuals with planned semaglutide treatment as a weight loss intervention |
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Ramy czasowe |
|---|---|
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Zmiana masy ciała (%)
Ramy czasowe: 16 tygodni
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16 tygodni
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
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Change in fat mass (%)
Ramy czasowe: 16 weeks
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measured by DEXA (dual energy x-ray absorptiometry) |
16 weeks
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Change in lean mass (%)
Ramy czasowe: 16 weeks
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measured by DEXA |
16 weeks
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Change in abdominal visceral fat area (in cm2)
Ramy czasowe: 16 weeks
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measured by DEXA |
16 weeks
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Inne miary wyników
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Change in cell size of adipose tissue after 16 weeks of semaglutide treatment
Ramy czasowe: 16 weeks
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The size of adipocytes is a direct measure of adipose tissue quality and function. It will be evaluated through histological examinations. |
16 weeks
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Changes in cell distribution of adipose tissue after 16 weeks of semaglutide treatment
Ramy czasowe: 16 weeks
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Changes in the distribution of adipocytes and other components of adipose tissue (e.g. macrophages, progenitors) serve as a direct measure of adipose tissue quality and function. It will be evaluated through histological examinations. |
16 weeks
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Changes in signs of fibrosis in adipose tissue after 16 weeks of semaglutide treatment
Ramy czasowe: 16 weeks
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Signs of fibrosis are a direct measure of adipose tissue quality and function. They will be evaluated through histopathological analysis. |
16 weeks
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Changes in inflammatory activity of adipose tissue after 16 weeks of semaglutide treatment
Ramy czasowe: 16 weeks
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Inflammatory activity, measured by the number and type of white blood cells infiltrating adipose tissue, is a direct way to assess adipose tissue quality and function. It will be evaluated by quantifying inflammatory cells within the tissue. |
16 weeks
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Change in adipokine secretion pattern after 16 weeks of semaglutide treatment
Ramy czasowe: 16 weeks
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The adipokine-secretion pattern is an indirect way to assess adipose tissue quality and function. We will analyze leptin, adipokines, and other relevant markers in blood samples and potentially in adipose tissue from strong or weak responders to identify patterns that may help predict significant changes or the absence of response. |
16 weeks
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Change in systemic inflammation after 16 weeks of semaglutide treatment
Ramy czasowe: 16 weeks
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Adipose tissue dysfunction can contribute to systemic inflammation, making it an indirect measure of adipose tissue quality. Serum levels of systemic inflammatory markers such as C-reactive protein (CRP), interleukins, and tumor necrosis factor-alpha (TNF-α) will be assessed before and after 16 weeks of semaglutide treatment. |
16 weeks
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Współpracownicy i badacze
Sponsor
Śledczy
- Krzesło do nauki: Christian Wolfrum, Prof. Dr., ETH Zurich
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Zakończenie podstawowe (Rzeczywisty)
Ukończenie studiów (Rzeczywisty)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- 2024-02395
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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