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

NCT ID: NCT05631444

Last Updated: 2022-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-01

Study Completion Date

2022-10-28

Brief Summary

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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

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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).

Conditions

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Chronic Limb-threatening Ischemia Diabetes Mellitus

Keywords

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Bone marrow mononuclear cells Mesenchymal stem cells

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

Cell-based therapy

Intervention Type BIOLOGICAL

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.

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.

Group Type EXPERIMENTAL

Cell-based therapy

Intervention Type BIOLOGICAL

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.

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.

Group Type EXPERIMENTAL

Cell-based therapy

Intervention Type BIOLOGICAL

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.

Interventions

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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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle

OTHER

Sponsor Role lead

Responsible Party

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Martha Ligia Arango Rodríguez

Director Technical and Scientific Centro de Terapias Avanzadas Fundación Ofalmológica de Santander (FOSCAL)

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martha L Arango, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle

Locations

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Fundación Oftalmológica de Santander (FOSCAL)

Bucaramanga, , Colombia

Site Status

Countries

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Colombia

References

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Arango-Rodriguez ML, Mateus LC, Sossa CL, Becerra-Bayona SM, Solarte-David VA, Ochoa Vera ME, Viviescas LTG, Berrio AMV, Serrano SE, Vargas O, Isla AC, Benitez A, Rangel G. A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells. Stem Cell Res Ther. 2023 Aug 25;14(1):221. doi: 10.1186/s13287-023-03427-z.

Reference Type DERIVED
PMID: 37626416 (View on PubMed)

Other Identifiers

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CLTI 01

Identifier Type: -

Identifier Source: org_study_id