Quantitative Hyperpolarized [1-13C]Pyruvate MRI for Metabolic Imaging in Diabetic Kidney Disease: A Study on Pyruvic Acid and Meglumine Gadoterate

The primary objective of this study is to evaluate the potential of **quantitative hyperpolarized [1-13C]pyruvate MRI** in classifying the progression of **Diabetic Kidney Disease**. This is clinically relevant as it may provide a non-invasive method to monitor disease progression, potentially leading to improved patient management and treatment outcomes.

Secondary objectives include: - Assessing the reproducibility of hyperpolarized [1-13C]pyruvate MRI in healthy subjects. - Evaluating whether expired CO2 measures enhance the clinical utility of hyperpolarized [1-13C]pyruvate MRI. - Investigating the correlation between metabolism and perfusion assessments using hyperpolarized [1-13C]pyruvate MRI and renal function in humans. - Comparing quantitative hyperpolarized [1-13C]pyruvate perfusion with the gold standard of water PET perfusion.

The clinical trial involves participants diagnosed with **Diabetic Kidney Disease** and aims to explore the progression of this condition using advanced imaging techniques. The study population includes both male and female subjects, aged between 18 and 85 years. Participants are selected based on specific health criteria, including those with Type 1 Diabetes Mellitus with or without diabetic kidney disease, as well as control subjects. The trial does not involve vulnerable populations. Participants with diabetic kidney disease must have an estimated glomerular filtration rate (eGFR) between 15 and 60 ml/min and a urine albumin-creatinine ratio greater than 100 mg/g. Those with Type 1 diabetes without kidney disease must have an eGFR greater than 60 ml/min and no albuminuria, along with no signs of proliferative retinopathy or macular edema. Control subjects are required to have an eGFR greater than 60 ml/min. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of **hyperpolarized [1-13C]pyruvate** in the assessment of **diabetic kidney disease** progression through quantitative MRI imaging. This is a Phase 4, randomized, double-blind, controlled trial. The trial will involve the administration of **hyperpolarized [1-13C]pyruvate** and **gadoteric acid** via intravenous infusion. The trial is expected to commence recruitment on January 1, 2024, and is estimated to conclude by August 1, 2029.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, presence of **type 1 diabetes mellitus**, and kidney function parameters. The primary endpoint is the metabolism and perfusion of the kidney as measured by hyperpolarized pyruvate, with secondary endpoints including the glomerular filtration rate and the reproducibility of the MRI technique. Follow-up visits will be scheduled to monitor the participants' response to the treatment and to collect data on the primary and secondary endpoints. The end-of-study visit will mark the completion of the trial for each participant, where final assessments will be conducted.

The expected length of participant involvement is determined by the trial's duration, with individual participation potentially lasting until the trial's conclusion in 2029. Conditions that may lead to early termination from the study include adverse reactions to the investigational products, non-compliance with study protocols, or withdrawal of consent by the participant. The trial aims to provide valuable insights into the potential of hyperpolarized pyruvate MRI in classifying the progression of diabetic kidney disease, thereby contributing to the advancement of diagnostic imaging techniques in this field.

The clinical trial involves the administration of **Hyperpolarized [1-13C]pyruvate**, an investigational medicinal product, which is formulated as an **injection**. The active substance in this product is **pyruvic acid**, originating from a chemical source. The administration route is via **intravenous infusion**, with a dosage of 0.43 milliliters per kilogram. The maximum treatment period is limited to one day. This product is not a pediatric formulation and is not classified as an orphan drug. The trial aims to evaluate the efficacy of this compound in the context of diabetic kidney disease.

In addition to the experimental treatment, the study utilizes **Gadoteric Acid**, also known as **meglumine gadoterate**, as a comparator treatment. This substance is also administered as an **intravenous infusion**. The dosage is set at 0.10 millimoles per kilogram, with a maximum treatment period of one day. This product is not a pediatric formulation and is not classified as an orphan drug. The use of Gadoteric Acid serves as a standard-of-care therapy to provide a baseline for evaluating the effects of the experimental treatment.

Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol. The trial is designed to assess the potential of hyperpolarized [1-13C]pyruvate in providing quantitative imaging insights into the progression of diabetic kidney disease, with the comparator treatment serving to validate the imaging results obtained.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint focuses on the **metabolism and perfusion of the kidney** using hyperpolarized [1-13C]pyruvate. This will be evaluated through advanced imaging techniques, specifically magnetic resonance imaging (MRI), to provide quantitative data on renal function and metabolic activity. Secondary endpoints include the measurement of Glomerular Filtration Rate (GFR) via renography and the reproducibility of hyperpolarized pyruvate MRI. These endpoints are designed to provide a comprehensive assessment of renal function and the potential impact of the investigational product on diabetic kidney disease.