Bone Marrow Mononuclear Cells vs Mesenchymal Stem Cells in Diabetic Patients With Chronic Limb Ischemia

Phase 1

Completed

• Conditions: Diabetes Mellitus; Chronic Limb-threatening Ischemia
• Interventions: Biological: Cell-based therapy

• Registration Number: NCT05631444
• Lead Sponsor: Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle

Brief Summary

Patients in the severe stages of Chronic limb-threatening ischemia (CLTI) are prone to amputation and death, leading to poor quality of life and a great socioeconomic burden.

There is an urgent need to develop an effective therapeutic strategy to treat this disease. In this context, autologous bone marrow mononuclear cells (BM-MNC) and allogeneic mesenchymal stem cells derived from different sources have emerged as promising therapeutic approaches for this condition.

Detailed Description

Comparison of the therapeutic potential of BM-MNC vs. allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) in diabetic patients with CLTI.

Twenty-four type 2 diabetic patients in the most severe stages of the CLTI (category 4 or 5 in Rutherford's classification and transcutaneous oxygen pressure (TcPO2) below 30 mm Hg were enrolled and randomized to receive 15 injections of (i) BM-MNC (7.197x106 ± 2.984 x106 cells/mL each with 2% of autologous serum) (n=7), (ii) allo-WJ-MSCs (1.333 x106 cells/mL each with 5% of human serum albumin serum) (n=7) or (iii) placebo solution (1 mL saline solution with 2% of autologous serum) (n=10), which were administered into the periadventitial arteries.

The follow-up visits were at months 1, 3, 6, and 12, to evaluate the following parameters:

(i) Rutherford classification (0 to 6) (ii) TcPO2 (mmHg) (iii) Wound closure (area cm2) (iv) pain (visual analogue scale (0-10) (v) pain-free walking distance (m) (vi) revascularization and limb-survival proportion during follow-up (vii) the quality of life (EQ-5D questionnaire).

Study Timeline

• Study Start: 2019-01-01
• Primary Completion: 2020-09-30
• Study Completion: 2022-10-28
• Study First Submitted: 2022-10-30
• Status Verified: 2022-11
• Study First Submitted QC: 2022-11-20
• Last Update Submitted: 2022-11-20
• Study First Posted: 2022-11-30
• Last Update Posted: 2022-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Adult male or female, 40 years of age or over (until 85 years old)
• TcPO2 ≤ 30 mmHg.
• Diagnosis of diabetes.
• Patients with signs of critical ischemia such as (i) ulcer that does not heal, (ii) necrosis or loss of tissue, (iii) pain at rest, and (iv) intermittent claudication.
• Basal Rutherford classification stage 3 to 5.
• Non-revascularizable patients due to comorbidities and/or anatomy.
• Patients that despite revascularization (vascular surgery), have adequate distal beds to perfuse the limb.
• Ankle/brachial index less than 0.4.
• Stenosis or occlusion of the infrapatellar arteries.

Exclusion Criteria

• Participants that do not sign the informed consent.
• Presence of osteomyelitis.
• Hemodynamic instability (MAP<65 mmHg or vasopressor requirement).
• Any acute systemic infectious disease process.
• Severe sepsis.
• Uncontrolled coagulopathy.
• Condition of cancer.
• Use of immunosuppressive or cytotoxic drugs
• Alterations of the bone marrow that do not allow the adequate extraction of the components to be used as: acute leukemia, chronic leukemia, marrow aplasia, myelodysplastic syndrome, and myelophthisis.
• Contraindication of sedation for bone marrow aspirate.
• Patients who have suffered in a period < six months of myocardial infarction, disease cerebrovascular or coronary intervention.
• Patients with liver failure indicated by serum transaminases (aspartate aminotransferase and alanine aminotransferase), with values twice the normal limit.
• Any acute or chronic contagious disease including hepatitis B, hepatitis C, and HIV.
• Any other comorbidity that the treating vascular surgeon considers as a contraindication to cell treatments.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	Cell-based therapy	Placebo group (n=10), which consisted of 15 injections of 1 mL of vehicle (1 mL saline solution with 2% of autologous serum) on periadventitial arteries in one dose at day 0.
Allo-WJ-MSCs	Cell-based therapy	Allo-WJ-MSCs (n=7) were obtained from culturing the WJ from healthy cordon umbilical donors unrelated to the patient. Fifteen injections of 1.333x106 cells/mL each with 5% of human serum albumin serum were periadventitial arteries administrated in one dose at day 0.
Auto-BM-MNC	Cell-based therapy	Auto-BM-MNC (n=7) were obtained from diabetic patients. Fifteen injections of 7.197x106 ± 2.984x106 cells/mL each with 2% of autologous serum were periadventitial arteries administrated in one dose at day 0.

Primary Outcome Measures

Name	Time	Method
Efficacy profile: Pain-free walking distance	12 months	meters
Efficacy profile: Rutherford's classification	12 months	0 to 6
TcPO2	12 months	mmHg
Safety profile: (adverse events (AEs) and serious AEs)	12 months	AEs: (i) local toxicity, including signs of local inflammation (swelling, warmth, impairment of function), worsening of ulcer, new ulcer, or hematomas after auto-BM-MNC or allo-WJ-MSCs administration.; (ii) systemic toxicity as fever, allergies. (iii) maximum grade toxicity for tissue.
Safety profile	12 months	Serious AEs: hospitalization, malignancy, amputation, persistent or significant disability, or death.
Efficacy profile: Visual Analogue Scale pain	12 months	0 to10
Efficacy profile: Limb survival proportion	12 months	Percentage
Efficacy profile: Quality of life	12 months	EQ-5D questionnaire
Efficacy profile: Wound closure	12 months	cm2
Efficacy profile: Revascularization	12 months	Percentage

Trial Locations

Locations (1)

Fundación Oftalmológica de Santander (FOSCAL); 🇨🇴 Bucaramanga, Colombia