A Randomized Controlled Trial on the Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy in Subjects With Moderate to Severe Diabetic Peripheral Neuropathy

Inclusion criteria

• Males or females aged 18-80 years;
• Meeting the 2023 ADA diagnostic criteria for type 2 diabetes;
• Presence of symptoms and signs of diabetic neuropathy in lower extremities:

For symptomatic patients: At least one abnormal finding among ankle reflex, pinprick sensation, vibration sense, pressure perception, or temperature sensation, accompanied by clinical symptoms (e.g., symmetric lower limb numbness, pain, or tingling); For asymptomatic patients: At least two abnormal findings in the above five examinations;

• Confirmed neurophysiological dysfunction:

Reduced nerve conduction velocity (≥2 standard deviations) in at least one lower extremity nerve (common peroneal, posterior tibial, or deep peroneal nerve), with or without decreased amplitude;

Moderate to severe neuropathy severity:

• Toronto Clinical Scoring System (TCSS) score ≥9;
• Inadequate response to conventional therapy: Persistent symptoms (reduction of TCSS score <2 points from baseline) despite ≥3 months of conventinal treatment;
• Capacity to understand and voluntarily complete all study procedures and interventions, with signed informed consent.

Exclusion criteria

• Non-diabetic neuropathy or pain conditions in lower limbs that may confound DPN assessment per investigator's judgment;
• Poorly controlled diabetes (HbA1c >12%);
• Severe hematological, hepatic, or renal dysfunction, meeting any of the following laboratory criteria:

Hematology: Neutrophils <1.5×10⁹/L, platelets <90×10⁹/L, or hemoglobin <80 g/L; Liver function: ALT or AST >3× upper limit of normal (ULN), or total bilirubin >1.5× ULN; Renal function: eGFR <30 mL/min/1.73m² (calculated by MDRD formula) or requiring renal replacement therapy; Creatine kinase >2× ULN;

• Known allergy to stem cells, stem cell-derived products, or components of stem cell preparations;
• Current use of prohibited medications within 5 half-lives prior to enrollment (may be reconsidered after ≥5 half-lives washout);
• Uncontrolled systemic diseases, including but not limited to: Severe uncontrolled systemic infections (bacterial, fungal, or viral); Severe autoimmune disorders; Hematological diseases; Heart failure (NYHA class ≥III);
• Clinically significant arrhythmia on 12-lead ECG;
• Conditions requiring amputation (e.g., severe diabetic foot or lower limb ulcers) that preclude local stem cell injection;
• Other diseases unsuitable for trial participation (e.g., active malignancy, cognitive impairment, depression, or psychiatric disorders);
• Participation in any interventional clinical trial within 3 months prior to screening;
• Pregnancy, lactation, or planning pregnancy within 2 years;
• Any other condition deemed by the investigator to compromise trial suitability.