search
Back to results

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

Primary Purpose

Chronic Limb-threatening Ischemia, Diabetes Mellitus

Status
Completed
Phase
Phase 1
Locations
Colombia
Study Type
Interventional
Intervention
Cell-based therapy
Sponsored by
Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Limb-threatening Ischemia focused on measuring Bone marrow mononuclear cells, Mesenchymal stem cells

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Fundación Oftalmológica de Santander (FOSCAL)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo group

Auto-BM-MNC

Allo-WJ-MSCs

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Safety profile: (adverse events (AEs) and serious AEs)
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
Serious AEs: hospitalization, malignancy, amputation, persistent or significant disability, or death.
Efficacy profile: Rutherford's classification
0 to 6
TcPO2
mmHg
Efficacy profile: Visual Analogue Scale pain
0 to10
Efficacy profile: Pain-free walking distance
meters
Efficacy profile: Wound closure
cm2
Efficacy profile: Revascularization
Percentage
Efficacy profile: Limb survival proportion
Percentage
Efficacy profile: Quality of life
EQ-5D questionnaire

Secondary Outcome Measures

Full Information

First Posted
October 30, 2022
Last Updated
November 20, 2022
Sponsor
Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
search

1. Study Identification

Unique Protocol Identification Number
NCT05631444
Brief Title
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
January 1, 2019 (Actual)
Primary Completion Date
September 30, 2020 (Actual)
Study Completion Date
October 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Limb-threatening Ischemia, Diabetes Mellitus
Keywords
Bone marrow mononuclear cells, Mesenchymal stem cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Auto-BM-MNC
Arm Type
Experimental
Arm Description
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.
Arm Title
Allo-WJ-MSCs
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Cell-based therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety profile: (adverse events (AEs) and serious AEs)
Description
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.
Time Frame
12 months
Title
Safety profile
Description
Serious AEs: hospitalization, malignancy, amputation, persistent or significant disability, or death.
Time Frame
12 months
Title
Efficacy profile: Rutherford's classification
Description
0 to 6
Time Frame
12 months
Title
TcPO2
Description
mmHg
Time Frame
12 months
Title
Efficacy profile: Visual Analogue Scale pain
Description
0 to10
Time Frame
12 months
Title
Efficacy profile: Pain-free walking distance
Description
meters
Time Frame
12 months
Title
Efficacy profile: Wound closure
Description
cm2
Time Frame
12 months
Title
Efficacy profile: Revascularization
Description
Percentage
Time Frame
12 months
Title
Efficacy profile: Limb survival proportion
Description
Percentage
Time Frame
12 months
Title
Efficacy profile: Quality of life
Description
EQ-5D questionnaire
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martha L Arango, PhD
Organizational Affiliation
Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fundación Oftalmológica de Santander (FOSCAL)
City
Bucaramanga
Country
Colombia

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs