Evaluation of Tirzepatide on Renal Oxygenation in Overweight or Obese Patients with Chronic Kidney Disease, with or without Type 2 Diabetes

The primary objective of this study is to compare the effect of **tirzepatide** at its maximum tolerated dose (MTD) administered weekly (QW) versus placebo on kidney oxygenation after 52 weeks of treatment in participants with and without **Type 2 Diabetes** (T2D). This is clinically relevant as it aims to assess the potential renal benefits of tirzepatide in individuals with **Chronic Kidney Disease** (CKD), particularly in the context of kidney hypoxia, which is a critical factor in the progression of CKD. The study focuses on individuals with **overweight** or **obesity**, conditions that are often associated with CKD and T2D, thereby addressing a significant clinical need for effective management strategies in this population.

The clinical trial involves a total of **96 participants** who are being studied to assess the effect of tirzepatide MTD QW and placebo on kidney oxygenation over a 52-week period. The study population includes both **male and female** subjects, with an age range that encompasses adults and older adults. Participants have been selected based on specific health conditions, including **Chronic Kidney Disease**, **Type 2 Diabetes**, and **Obesity** or being **Overweight**. The trial requires that half of the participants have Type 2 Diabetes, while the other half do not. The selection process ensures a diverse representation of individuals with these conditions. Lifestyle factors such as diet and physical activity are not explicitly detailed, but the inclusion of individuals with obesity or overweight suggests a consideration of these aspects. The trial includes a vulnerable population, indicating careful ethical considerations in participant selection.

The clinical trial is designed to evaluate the effect of **tirzepatide** on kidney oxygenation in participants with **chronic kidney disease** (CKD), with or without **type 2 diabetes** (T2D), over a period of 52 weeks. This is a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial will involve the administration of tirzepatide as a **solution for injection** via the subcutaneous route, with a placebo group for comparison. The primary endpoint is the change from baseline in kidney oxygenation, assessed using blood oxygenation-level dependent magnetic resonance imaging (BOLD MRI) at baseline and at week 52.

Participants will be involved in the study for approximately 52 weeks, with the trial expected to conclude by December 2026. The study will begin with an inclusion visit, where participants will be screened based on criteria such as having obesity or overweight, CKD, and a balanced representation of individuals with and without T2D. Following the inclusion visit, participants will undergo regular follow-up visits to monitor their health status and treatment effects. The end-of-study visit will occur at the conclusion of the 52-week treatment period, where final assessments will be conducted.

Participants may be withdrawn from the study early if they experience adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial is categorized as a Phase 4 study, focusing on a new indication for an authorized investigational medicinal product. The trial's main objective is to compare the effect of tirzepatide and placebo on kidney oxygenation, providing valuable insights into the potential benefits of tirzepatide for individuals with CKD and related conditions.

The clinical trial involves the administration of **Tirzepatide**, a **solution for injection** developed by Eli Lilly and Company. Tirzepatide is a protein-based therapeutic agent, specifically classified as "Protein - Other." The pharmaceutical form is a solution for injection, and it is administered subcutaneously. The dosing schedule is weekly, with a maximum treatment period of one year. The specific dosage and total dose amounts are not specified in the provided data. Compliance with the administration schedule is monitored through the use of a device, although the device does not have a CE mark.

A **placebo** is used in the trial to match the experimental product, LY3298176. The placebo is designed to mimic the appearance and administration route of Tirzepatide, ensuring blinding in the study. The placebo does not contain any active pharmaceutical ingredients and serves as a control to evaluate the efficacy and safety of Tirzepatide.

Additionally, **Iohexol** is utilized as an auxiliary substance in the trial. Iohexol is a chemical compound used in the form of a solution for injection. It is administered with a maximum daily dose of 647 mg/ml and a maximum total dose of 1294 mg/ml. The treatment period for Iohexol is limited to two days. The administration route is consistent with the solution for injection form, and it is used to facilitate imaging studies within the trial.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the change from baseline in kidney oxygenation in participants with or without type 2 diabetes (T2D). This will be measured using blood oxygenation-level dependent magnetic resonance imaging (BOLD MRI). The time frame for this assessment includes baseline and week 52 of the treatment period. The trial aims to compare the effect of **tirzepatide** administered at the maximum tolerated dose (MTD) once weekly (QW) against a placebo on kidney oxygenation after 52 weeks of treatment. The study population includes individuals with obesity or overweight and chronic kidney disease, with half of the participants having T2D and the other half not having T2D. The efficacy assessments will be conducted using validated imaging techniques to ensure accurate and reliable data collection and analysis.