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 (RELEASE-DPN)

Min Long

Status and phase: Not yet enrolling; Phase 2

Conditions: Diabetic Peripheral Neuropathy (DPN)

Treatments: Drug: Conventional therapy group; Biological: Experimental Group

Study type: Interventional

Funder types: Other

Identifiers

NCT07183761

2023ZD0509004-4.1

Details and patient eligibility

About

This clinical trial aims to evaluate the efficacy and safety of human umbilical cord mesenchymal stem cell (hUC-MSC) injection in the treatment of adults with moderate to severe diabetic peripheral neuropathy.

Researchers will compare hUC-MSCs injection combined with conventional therapy (experimental group) to conventional therapy alone (control group) to see if hUC-MSCs work to treat diabetic peripheral neuropathy.

The experimental group will receive three injections of hUC-MSCs (on Day 0, Day 7, and Day 28) while continuing conventional therapy, whereas the control group will receive conventional therapy only. Participants will undergo regular follow-ups for checkups and tests over a 24-week period. The primary endpoint of the study is the change in the Toronto Clinical Scoring System (TCSS) score at Week 24. Safety assessments will be conducted throughout the entire study period, with extended follow-up until Week 104 to evaluate long-term safety.

Enrollment: 140 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males or females aged 18-80 years;

2. Meeting the 2023 ADA diagnostic criteria for type 2 diabetes;

3. 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;

4. 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:

5. Toronto Clinical Scoring System (TCSS) score ≥9;

6. Inadequate response to conventional therapy: Persistent symptoms (reduction of TCSS score <2 points from baseline) despite ≥3 months of conventinal treatment;

7. Capacity to understand and voluntarily complete all study procedures and interventions, with signed informed consent.

Exclusion criteria

1. Non-diabetic neuropathy or pain conditions in lower limbs that may confound DPN assessment per investigator's judgment;

2. Poorly controlled diabetes (HbA1c >12%);

3. 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;

4. Known allergy to stem cells, stem cell-derived products, or components of stem cell preparations;

5. Current use of prohibited medications within 5 half-lives prior to enrollment (may be reconsidered after ≥5 half-lives washout);

6. 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);

7. Clinically significant arrhythmia on 12-lead ECG;

8. Conditions requiring amputation (e.g., severe diabetic foot or lower limb ulcers) that preclude local stem cell injection;

9. Other diseases unsuitable for trial participation (e.g., active malignancy, cognitive impairment, depression, or psychiatric disorders);

10. Participation in any interventional clinical trial within 3 months prior to screening;

11. Pregnancy, lactation, or planning pregnancy within 2 years;

12. Any other condition deemed by the investigator to compromise trial suitability.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

Experimental group

Experimental group

Description:

The experimental group will receive three injections of hUC-MSCs (on Day 0, Day 7, and Day 28) while continuing conventional therapy.

Treatment:

Biological: Experimental Group

Drug: Conventional therapy group

Control group

Active Comparator group

Description:

The control group will receive conventional therapy only.

Treatment:

Drug: Conventional therapy group