Clinical trial NCT05631444: Bone Marrow Mononuclear Cells vs Mesenchymal Stem Cells in Diabetic Patients With Chronic Limb Ischemia
Official title: Comparison of the Therapeutic Potential of Autologous Bone Marrow Mononuclear Cells Versus Allogenic Wharton Jelly-derived Mesenchymal Stem Cells in Diabetic Patients With Chronic Limb-threatening Ischemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Limb-threatening Ischemia
Diabetes Mellitus
Keywords: Bone marrow mononuclear cells
Mesenchymal stem cells
Lead sponsor: Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
Sponsor class: OTHER
First posted: 2022-11-30
Enrollment: 24
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Safety profile: (adverse events (AEs) and serious AEs)
timeFrame: 12 months
measure: Safety profile
timeFrame: 12 months
measure: Efficacy profile: Rutherford's classification
timeFrame: 12 months
measure: TcPO2
timeFrame: 12 months
measure: Efficacy profile: Visual Analogue Scale pain
timeFrame: 12 months
measure: Efficacy profile: Pain-free walking distance
timeFrame: 12 months
measure: Efficacy profile: Wound closure
timeFrame: 12 months
measure: Efficacy profile: Revascularization
timeFrame: 12 months
measure: Efficacy profile: Limb survival proportion
timeFrame: 12 months
measure: Efficacy profile: Quality of life
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Bucaramanga
country: Colombia
facility: Fundación Oftalmológica de Santander (FOSCAL)
Study officials:
affiliation: Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
name: Martha L Arango, PhD
role: PRINCIPAL_INVESTIGATOR
References: