Bone Marrow Mononuclear Cells vs Mesenchymal Stem Cells in Diabetic Patients With Chronic Limb Ischemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo group 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. |
Biological: Cell-based therapy
One dose of auto-BM-MNC, one dose of allo-WJ-MSCs, or one dose of placebo solution (saline solution with 2% of autologous serum), were periadventitial arteries administration in CTLI patients.
|
| Experimental: Auto-BM-MNC 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. |
Biological: Cell-based therapy
One dose of auto-BM-MNC, one dose of allo-WJ-MSCs, or one dose of placebo solution (saline solution with 2% of autologous serum), were periadventitial arteries administration in CTLI patients.
|
| Experimental: Allo-WJ-MSCs 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. |
Biological: Cell-based therapy
One dose of auto-BM-MNC, one dose of allo-WJ-MSCs, or one dose of placebo solution (saline solution with 2% of autologous serum), were periadventitial arteries administration in CTLI patients.
|
Outcome Measures
Primary Outcome Measures
- 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: Rutherford's classification [12 months]
0 to 6
- TcPO2 [12 months]
mmHg
- Efficacy profile: Visual Analogue Scale pain [12 months]
0 to10
- Efficacy profile: Pain-free walking distance [12 months]
meters
- Efficacy profile: Wound closure [12 months]
cm2
- Efficacy profile: Revascularization [12 months]
Percentage
- Efficacy profile: Limb survival proportion [12 months]
Percentage
- Efficacy profile: Quality of life [12 months]
EQ-5D questionnaire
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adult male or female, 40 years of age or over (until 85 years old)
-
TcPO2 ≤ 30 mmHg.
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Diagnosis of diabetes.
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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.
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Basal Rutherford classification stage 3 to 5.
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Non-revascularizable patients due to comorbidities and/or anatomy.
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Patients that despite revascularization (vascular surgery), have adequate distal beds to perfuse the limb.
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Ankle/brachial index less than 0.4.
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Stenosis or occlusion of the infrapatellar arteries.
Exclusion Criteria:
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Participants that do not sign the informed consent.
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Presence of osteomyelitis.
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Hemodynamic instability (MAP<65 mmHg or vasopressor requirement).
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Any acute systemic infectious disease process.
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Severe sepsis.
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Uncontrolled coagulopathy.
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Condition of cancer.
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Use of immunosuppressive or cytotoxic drugs
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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.
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Contraindication of sedation for bone marrow aspirate.
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Patients who have suffered in a period < six months of myocardial infarction, disease cerebrovascular or coronary intervention.
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Patients with liver failure indicated by serum transaminases (aspartate aminotransferase and alanine aminotransferase), with values twice the normal limit.
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Any acute or chronic contagious disease including hepatitis B, hepatitis C, and HIV.
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Any other comorbidity that the treating vascular surgeon considers as a contraindication to cell treatments.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fundación Oftalmológica de Santander (FOSCAL) | Bucaramanga | Colombia |
Sponsors and Collaborators
- Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
Investigators
- Principal Investigator: Martha L Arango, PhD, Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CLTI 01