Autologous Peripheral Blood Mononuclear Cells in Diabetic Foot Patients With No-option Critical Limb Ischemia

NCT04255004 | Completed

• 1 other identifier: MONODIAB-19-01
• Study Type: interventional
• Target: 76
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this trial is to determine whether PBMNCs in diabetic patients with critical, non revascularizable limb ischemia can prevent major amputation and affect mortality and healing.

Conditions

Critical Limb Ischemia; Diabetic Foot

Keywords

autologous peripheral blood mononuclear cell, diabetic foot

Outcome Measures

Primary Outcomes (18)

• Amputation-free survival at 1 month

  rate of non amputated limb 1 month after the intervention

  1 month

• Amputation-free survival at 3 months

  rate of non amputated limb 3 months after the intervention

  3 months

• Amputation-free survival at 6 months

  rate of non amputated limb 6 months after the intervention

  6 months

• Amputation-free survival at 12 months

  rate of non amputated limb 12 months after the intervention

  12 months

• Amputation-free survival at 18 months

  rate of non amputated limb 18 months after the intervention

  18 months

• Amputation-free survival at 24 months

  rate of non amputated limb 24 months after the intervention

  24 months

• risk of death at 1 month

  rate of dead subjects 1 month after the intervention

  1 month

• risk of death at 3 months

  rate of dead subjects 3 months after the intervention

  3 months

• risk of death at 6 months

  rate of dead subjects 6 months after the intervention

  6 months

• risk of death at 12 months

  rate of dead subjects 12 months after the intervention

  12 months

• risk of death at 18 months

  rate of dead subjects 18 months after the intervention

  18 months

• risk of death at 24 months

  rate of dead subjects 24 months after the intervention

  24 months

• probability of healing at 1 month

  rate of healed subjects 1 month after the intervention

  1 month

• probability of healing at 3 months

  rate of healed subjects 3 months after the intervention

  3 months

• probability of healing at 6 months

  rate of healed subjects 6 months after the intervention

  6 months

• probability of healing at 12 months

  rate of healed subjects 12 months after the intervention

  12 months

• probability of healing at 18 months

  rate of healed subjects 18 months after the intervention

  18 months

• probability of healing at 24 months

  rate of healed subjects 24 months after the intervention

  24 months

Secondary Outcomes (3)

• transcutaneous oxygen measurement (TcPO2) variation

  0-3 months

• Healing time

  within 24 months

• rest pain

  0-1-3 months

Study Arms (2)

A-PBMNC therapy

ACTIVE COMPARATOR

Patients in A-PBMNC therapy are treated with wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses). This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.

Device: Pall Celeris System, point of care device for human cell therapy

No A-PBMNC therapy

NO INTERVENTION

Patients in No A-PBMNC therapy receive only supportive treatment including wound care and pain killer drug.

Interventions

Pall Celeris System, point of care device for human cell therapy DEVICE

Concentration of PB-MNCs autologous cell therapy was produced by a filtration-based point-of-care device. All the procedures were performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) was collected through a peripheral venous access. Blood was loaded, and gravity filtration was allowed to proceed until the upstream side of the filter had no remaining blood; filtration last about 10 minutes. During filtration, MNCs were captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) were not retained. Immediately concentrate solution is injected in the perilesional area and intramuscular in the foot and the leg (0.2-0.3cc in boluses) below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.

A-PBMNC therapy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) \<30 mmHg;
• ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System
• not eligible for angioplasty or vascular surgery or following failed revascularization;
• possibility to save foot support.

You may not qualify if:

• lesion site above the tibial-tarsal joint;
• moderate or severe infection according by the WiFI classification system;
• NYHA class IV; d) Anemia (Hb\<8g/dl);
• coagulation disorder/thrombocytopenia (PLT\< 50,000 per microliter);
• active cancer/leukemia or lymphoma hematological disease.

Sponsors & Collaborators

• Ospedale San Donato: lead

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MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Diabetic Foot

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; Diabetic Angiopathies; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Leonardo Ercolini, MD

  Vascular Surgery Unit San Donato Hospital Arezzo

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: We would enroll a cohort of 38 consecutive diabetic patients with CLI in charge at the Diabetic Foot Unit of the San Donato Hospital in Arezzo or referred from other Italian hospitals, who have no option for revascularization or are not further eligible for revascularization according to ESVS ESC 2017 criteria to undergo PB-MNC implantation. Furthermore, an historical control group, with a 1:1 case-control ratio, will be collected backwards from our records, when PBMNCs cellular therapy was not available in our center, with same no-option CLI diagnosis.

Study Record Dates

• First Submitted: January 25, 2020
• First Posted: February 5, 2020
• Study Start: January 1, 2014
• Primary Completion: February 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 5, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share