Comparison of Autologous Bone Marrow-Derived Mononuclear Cells and Percutaneous Transluminal Angioplasty in Diabetic Patients with Chronic Limb-Threatening Ischemia

The primary objective of this clinical trial is to evaluate the **efficacy** of a combined treatment approach using autologous cell therapy and percutaneous transluminal angioplasty (PTA) compared to PTA alone in diabetic patients with **chronic limb-threatening ischemia**. The study aims to assess the rate of major amputation, wound healing, and transcutaneous oxygen pressure (TcPO2) as primary endpoints. These outcomes are clinically relevant as they directly impact the quality of life and limb preservation in patients suffering from this severe condition. The trial also seeks to identify potential side effects and complications associated with both treatment modalities.

The clinical trial involves participants diagnosed with **chronic limb-threatening ischemia** and **diabetic foot ulcers**. The study population includes both male and female subjects, aged between 18 and 90 years, who have been diagnosed with diabetes mellitus type 1 or 2. 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, and chronic limb-threatening ischemia due to arterial occlusive disease. The trial does not involve a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified. Key inclusion criteria include a TcPO2 under 40 mm Hg and an indication for percutaneous transluminal angioplasty (PTA). Female participants of childbearing potential are required to use a highly effective method of contraception during the study. The sponsor has not provided information on the total number of participants.

The clinical trial is designed to evaluate the **efficacy** of combined treatment using autologous cell therapy and percutaneous transluminal angioplasty (PTA) compared to PTA alone in patients with **chronic limb-threatening ischemia** and **diabetic foot ulcers**. This is a Phase 4, randomized, double-blind, controlled trial. The trial aims to assess the primary endpoints, which include the rate of major amputation, wound healing, and transcutaneous oxygen pressure (TcPO2). Secondary endpoints involve other ischemia parameters such as ankle-brachial index (ABI), laser Doppler flowmetry, magnetic resonance spectroscopy, and optional microbiopsy of the foot muscle. Additionally, the trial will evaluate clinical effects like pain, safety through adverse events, and quality of life using standardized questionnaires.

The trial is expected to commence recruitment on July 1, 2025, and conclude by December 30, 2028. Participants will be involved for a maximum treatment period of three months. The study will include several visits: an initial screening visit to confirm eligibility based on criteria such as age (18-90 years), presence of diabetes mellitus type 1 or 2, and signed informed consent. Females of childbearing potential must agree to use highly effective contraception throughout the study. Follow-up visits will monitor treatment effects and safety, with an end-of-study visit to assess final outcomes.

Participants may be withdrawn from the study if they experience significant adverse events or if they no longer meet the inclusion criteria. The investigational product, a suspension of autologous mononuclear cells derived from bone marrow aspirate, will be administered via intramuscular injection, with a maximum daily and total dose of 60 ml. The trial is not categorized as low intervention and is justified as an advanced therapy medicinal product (ATMP) trial focusing on safety, efficacy, and therapeutic outcomes.

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 is composed of **autologous bone marrow-derived mononuclear cells**. The cells are obtained from the patient's own bone marrow, making it a **cell therapy** product. The suspension is administered via **intramuscular injection**. The maximum daily dose is 60 ml, with a total maximum dose of 60 ml over a treatment period of up to 3 months. The administration schedule and participant compliance are closely monitored to ensure adherence to the dosing regimen.

In addition to the experimental treatment, the study includes a **comparator treatment** of percutaneous transluminal angioplasty (PTA), which serves as the standard-of-care therapy. The trial aims to evaluate the efficacy of the combined treatment of autologous cell therapy and PTA versus PTA alone in diabetic patients with chronic limb-threatening ischemia. The primary outcomes assessed include the rate of major amputation, wound healing, and transcutaneous oxygen pressure (TcPO2). The study is designed to monitor and assess any potential side effects and complications associated with both treatment methods.

The efficacy of the clinical trial will be assessed by comparing the combination of autologous cell therapy and percutaneous transluminal angioplasty (PTA) with PTA alone in diabetic patients with chronic limb-threatening ischemia. The primary efficacy endpoints include the rate of major amputation, wound healing, and transcutaneous oxygen pressure (**TcPO2**). These parameters will be measured to evaluate the effectiveness of the treatment interventions.

Secondary endpoints will include other ischemia parameters such as Ankle-Brachial Index (ABI), laser Doppler flowmetry, and magnetic resonance spectroscopy. Additionally, optional assessments may involve microbiopsy of the foot muscle. Clinical effects such as pain and safety, including both expected and unexpected adverse events, will also be evaluated. The assessment of quality of life will be conducted using standardized questionnaires. These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to determine the comparative effectiveness of the treatment modalities.