Clinical trial NCT05999656: Human Cord Blood Mononuclear Cells in the Treatment of Refractory Diabetic Foot
Official title: Clinical Study on the Safety and Efficacy of Local Injection of Human Cord Blood Mononuclear Cells in the Treatment of Refractory Diabetic Foot
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Refractory Diabetic Foot
Human Cord Blood-derived Mononuclear Cells
Efficacy
Safety
Local Injection
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Shandong Qilu Stem Cells Engineering Co., Ltd.
First posted: 2023-08-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Refractory diabetic foot is one of the most serious and costly chronic complications of diabetes. It is the leading cause of nontraumatic lower-extremity amputations while the conventional treatment is not effective. Therefore, new therapeutic methods are urgently needed. Cell therapy has shown unique advantages and potential in tissue regeneration and wound repair, and is considered as a new effective method to treat diabetic foot. Meanwhile, human cord blood-derived mononuclear cells (HCB-MNCs) with its sufficient sources, strong ability of proliferation and differentiation, and weak immunogenicity, is suitable for the treatment of diabetic foot. It is a prospective, single-arm, single-center clinical study to investigate the efficacy and safety of local injection of HCB-MNCs in the treatment of refractory diabetic foot.

Detailed description: Refractory diabetic foot is one of the most serious and costly chronic complications of diabetes, and is the leading cause of nontraumatic lower-extremity amputations. Conventional treatment is symptomatic supportive treatment such as controlling blood sugar, fighting infection, improving blood circulation, using topical medications, etc. But the effectiveness is barely satisfactory, while the wound heals slowly, and the large blood vessels that have been blocked cannot be re-opened. Therefore, an effective method is needed to relieve lower limb ischemia, promote ulcer healing and shorten the treatment time.

Cell therapy has shown unique advantages and potential in tissue regeneration and wound repair, and is considered as a new effective method to treat diabetic foot. Cell treatment for diabetic foot include local injection, intravenous infusion and arterial infusion. At present, local intramuscular injection is used in most studies at home and abroad.

HCB-MNCs is composed of immature immune cells and pluripotent stem cells, which is adequate, superior proliferative and immature , is a favorable source of cells for the treatment of diabetic foot. A few clinical studies have found that local intramuscular injection of HCB-MNCs or combined with gel dressing can effectively treat diabetic foot ulcers and relieve pain and other symptoms of patients. In this study, 24 patients with refractory diabetic foot will be enrolled. HCB-MNCs will be injected into the diabetic foot wound area 3 times at a week interval to explore its effectiveness and safety.

The primary objective of this study is to investigate the safety of local application of HCB-MNCs in the treatment of refractory diabetic foot and the change of wound area. The secondary objective is to assess changes in the visual analogue scale, total symptoms score and wagner scale.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18-80 years;
2. Meet the diagnostic criteria of diabetic foot by International Clinical Guidelines for Diabetic Foot;
3. Ulcer course ≥8 weeks, Wagner grade ≥2;
4. There was no healing trend (no reduction in wound size and no obvious new granulation tissue) after 4 weeks or above treatment. Or the ulcer was further aggravated (by Wagner's grade assessment) in the course of standardized treatment;
5. Fasting blood glucose ≤9mmol/L, 2h postprandial blood glucose ≤13mmol/L;
6. Signing informed consent.

Exclusion Criteria:

1. Patients with a history of ketoacidosis and hyperosmosis within 6 months;
2. Patients with viral infection (treponema pallidum, active hepatitis, HIV, Epstein-Barr virus, etc.)
3. Patients with malignant disease or cured of basal cell carcinoma within the past 5 years;
4. Creatinine clearance \< 45ml/min;
5. Patients with severe heart failure (NYHA III-IV);
6. Patients with a history of myocardial infarction or cerebral infarction in the last 3 months;
7. Patients who have received cell or growth factor therapy in the past year;
8. Patients during pregnancy or lactation;
9. Patients with abnormal thyroid dysfunction history or abnormal control through drug treatment;
10. Patients with severe hepatic failure (ALT, AST: above 3 times the upper limit of normal);
11. Lower extremity arterial with large artery occlusion by ultrasound image;
12. Patients with a history of severe coagulation disorder or hemorrhagic disease;
13. Patients with sequelae of cerebral infarction or other reasons that cannot extend their lower limbs flat;
14. Patients with psychological or mental disorders who cannot cooperate with treatment;
15. Participate in other clinical research within the past three months;
16. Patients are unable to complete the study or comply with the requirements of the study by investigator's judgment.

Primary outcomes:
measure: Number of patients with no adverse reactions.
timeFrame: From baseline to 12 weeks after the first treatment. The follow-up period can be extended up to 24 weeks if the patient's foot ulcers have not healed at 12 weeks.
measure: Rate of wound area change
timeFrame: From baseline to 12 weeks after the first treatment. The follow-up period can be extended up to 24 weeks if the patient's foot ulcers have not healed at 12 weeks.
Secondary outcomes:
measure: Change in visual analogue scale (VAS)
timeFrame: From baseline to 12 weeks after the first treatment. The follow-up period can be extended up to 24 weeks if the patient's foot ulcers have not healed at 12 weeks.
measure: Change in total symptoms score (TSS)
timeFrame: From baseline to 12 weeks after the first treatment. The follow-up period can be extended up to 24 weeks if the patient's foot ulcers have not healed at 12 weeks.
measure: Change in Wagner scale
timeFrame: From baseline to 12 weeks after the first treatment. The follow-up period can be extended up to 24 weeks if the patient's foot ulcers have not healed at 12 weeks.
Other outcomes:
Locations:
city: Nanjing
country: China
facility: the First Affiliated Hospital of Nanjing Medical University
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Tao Yang
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Xuqin Zheng
role: STUDY_DIRECTOR
References: