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

NCT05631444 | Completed Phase 1 DMC

• 1 other identifier: CLTI 01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Limb-threatening Ischemia; Diabetes Mellitus

Keywords

Bone marrow mononuclear cells; Mesenchymal stem cells

Outcome Measures

Primary Outcomes (10)

• 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.

  12 months

• Safety profile

  Serious AEs: hospitalization, malignancy, amputation, persistent or significant disability, or death.

  12 months

• Efficacy profile: Rutherford's classification

  0 to 6

  12 months

• TcPO2

  mmHg

  12 months

• Efficacy profile: Visual Analogue Scale pain

  0 to10

  12 months

• Efficacy profile: Pain-free walking distance

  meters

  12 months

• Efficacy profile: Wound closure

  cm2

  12 months

• Efficacy profile: Revascularization

  Percentage

  12 months

• Efficacy profile: Limb survival proportion

  Percentage

  12 months

• Efficacy profile: Quality of life

  EQ-5D questionnaire

  12 months

Study Arms (3)

Placebo group

PLACEBO COMPARATOR

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

Auto-BM-MNC

EXPERIMENTAL

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

Allo-WJ-MSCs

EXPERIMENTAL

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

Interventions

Cell-based therapy 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; Auto-BM-MNC; Placebo group

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle: lead

Study Sites (1)

Fundación Oftalmológica de Santander (FOSCAL)

Bucaramanga, Colombia

Location

Related Publications (1)

• 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.

  PMID: 37626416 DERIVED

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Diabetes Mellitus

Interventions

Cell- and Tissue-Based Therapy

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Martha L Arango, PhD

  Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Technical and Scientific Centro de Terapias Avanzadas Fundación Ofalmológica de Santander (FOSCAL)

Study Record Dates

• First Submitted: October 30, 2022
• First Posted: November 30, 2022
• Study Start: January 1, 2019
• Primary Completion: September 30, 2020
• Study Completion: October 28, 2022
• Last Updated: November 30, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)