Evaluation of Autologous Bone Marrow-Derived Mononuclear Cell Therapy Versus Standard Care in Diabetic Patients with Chronic Limb-Threatening Ischemia

The primary objective of this study is to compare the effect of **autologous bone marrow-derived mononuclear cell therapy** with standard treatment on tissue oxygenation and clinical outcomes in patients with chronic limb-threatening ischemia (CLTI) and diabetic foot ulcers (DFU) who are not eligible for percutaneous transluminal angioplasty (PTA). The study also aims to verify the effect of repetitive cell therapy. This is clinically relevant as it addresses the need for alternative therapeutic options in patients with limited treatment choices, potentially improving limb salvage and quality of life.

Secondary objectives include the assessment of quality of life and the evaluation of side effects associated with the study treatment. These objectives are important for understanding the broader impact of the therapy on patient well-being and safety.

The clinical trial involves participants diagnosed with **diabetic foot syndrome** and **lower limb ischemia**. The study population includes both male and female subjects, aged between 18 and 90 years, who are in general good health aside from their chronic conditions. The total number of participants is not provided by the sponsor. Participants were selected based on specific criteria, including the presence of diabetic foot ulcers or status after minor amputation, chronic limb-threatening ischemia due to arterial occlusive disease, and a diagnosis of diabetes mellitus type 1 or 2. All participants have provided signed informed consent. The trial does not include a vulnerable population, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy and safety of **autologous bone marrow-derived mononuclear cells** in comparison to standard treatment for patients with chronic limb-threatening ischemia and diabetic foot ulcers. This study is a randomized, double-blind, controlled trial, with an estimated duration from June 2020 to December 2027. Participants will be randomly assigned to receive either the investigational therapy or the standard treatment. The investigational product is administered as a **suspension for injection** via intramuscular injection, with a maximum daily dose of 60 ml and a treatment period of up to three months.

The trial includes several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility criteria such as age (18-90 years), presence of diabetic foot ulcers or ischemic rest pain, and chronic limb-threatening ischemia will be assessed. Participants must provide signed informed consent to be included in the study. Follow-up visits will be conducted to monitor the primary endpoints, which include the assessment of tissue oxygenation and clinical outcomes such as wound healing and amputation-free survival. Secondary endpoints will evaluate safety through adverse event monitoring and the relationship between cell suspension quality and tissue oxygenation.

The expected length of participant involvement is approximately three months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events that compromise participant safety, or any other protocol-defined criteria. The trial aims to provide valuable insights into the therapeutic potential of cell therapy in improving ischemia parameters in diabetic patients.

The clinical trial involves the administration of an **experimental medication** known as the "Suspension of autologous mononuclear cells separated from bone marrow aspirate." This medication is a **suspension for injection** and contains **autologous bone marrow-derived mononuclear cells** as the active substance. The cells are obtained from the patient's own bone marrow, making it a form of **cell therapy**. The pharmaceutical form is specifically designed for **intramuscular injection**. The maximum daily dose is 60 ml, with a total maximum dose of 60 ml over the treatment period. The treatment is administered over a maximum period of 3 months. The suspension is not a pediatric formulation and is not classified as an orphan drug.

In addition to the experimental treatment, the study includes a **standard treatment** as a comparator. This standard treatment is used to evaluate the effect of the autologous cell therapy on ischemia parameters in diabetic patients with chronic limb-threatening ischemia (CLTI) and diabetic foot ulcers (DFU) who are not eligible for percutaneous transluminal angioplasty (PTA). The trial aims to assess the impact on tissue oxygenation and clinical outcomes, as well as to verify the effect of repetitive cell therapy. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed by comparing the effects of autologous bone marrow-derived mononuclear cell therapy with standard treatment in patients with **chronic limb-threatening ischemia** and diabetic foot ulcers. The primary endpoints for evaluating efficacy include the assessment of tissue oxygenation and clinical outcomes. Tissue oxygenation will be measured by transcutaneous oxygen pressure (TcPO2) and optionally by other angiological methods to determine improvements in ischemia parameters. Clinical outcomes will be evaluated based on wound healing, changes in pain levels, the rate of major amputations, and amputation-free survival.

Secondary endpoints will focus on safety, including both expected and unexpected adverse events, and the assessment of study treatment by patients through psychological questionnaires. Additionally, the trial will explore the relationship between the quality of the cell suspension and tissue oxygenation. These efficacy parameters will be collected and analyzed throughout the trial duration, with specific timepoints and methods for measurement not explicitly detailed in the provided data.