Intraarterial Infusion of Autologous Bone Marrow in Diabetic Patients With Chronic Ischemia of Lower Limbs (CLI) no Revascularization

NCT ID: NCT00987363

Last Updated: 2016-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2013-03-31

Brief Summary

The aim of the study is to evaluate the safety and feasibility of autologous bone marrow mononuclear cells autologous administered intra-arterially in the affected limb of diabetic patients with chronic critical ischemia of the lower limbs (CLI) without possibility of revascularization or other therapeutic alternatives.

The trial hypothesis we propose consists of mononuclear cells of bone marrow providing progenitor cells with regenerative capacity and secrete also several angiogenic factors, and their implantation into ischemic tissues with both elements should contribute to angiogenesis and tissue regeneration with recovery of the circulation in the affected limb

Detailed Description

Phase II Clinical Trial, a prospective, multicenter, open, randomized, parallel-group controlled with three dose levels.

The study population will consist of a total of 60 diabetic patients with chronic critical ischemia of one leg (CLI) and no possibility of revascularization. In the experimental group will include a total of 45 patients divided into three dose levels, 15 patients in each level (increasing doses of mononuclear cells of bone marrow evenly) and 15 patients in control group (no cell therapy). Patients will be randomly assigned to either the control group or to any of the three experimental groups in which the dose of mononuclear cells of bone marrowo will be:

• Group 1(15 patients): no cell therapy.
• Group 2(15 patients): 1x108 mononuclear cells of bone marrow
• Gropu 3(15 patients): 5x108 mononuclear cells of bone marrow
• Group 4(15 patients): 1x109 mononuclear cells of bone marrow The cell therapy medicinal product shall be administered in all cases intraarterially.

Patients were evaluated by clinical, radiological and angiologist methods. This is a randomized controlled trial in which the safety and feasibility of cell therapy medicinal product shall be measured by comparing the response variables after treatment compared to baseline prior to implementation. Secondarily the results obtained are compared with each of the dose groups.

Patients will receive in a concomitant way the drug treatment established by the good practice, so it would certainly be possible that some improvement occurs due to drug treatment.

The primary variable is the improvement in the vascularización of the treated limb determined by clinical, angiologic and angiographic parameters.

It is estimated that the inclusion period lasts between twelve and eighteen months with twelve months follow-up. Therefore the total study duration range between twenty-four and thirty months from the inclusion of the first patient to the end of the follow-up of the last patient included.

Objectives of the study:

• Main objective: To evaluate the safety and feasibility of mononuclear cells of autologous bone marrow administered intra-arterially in the affected limb of diabetic patients with chronic critical ischemia of the lower limbs without possibility of revascularization or other therapeutic alternatives.

Secondary objectives:

Conditions

Critical Limb Ischemia (CLI); Diabetic Foot

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low dose (1x10 E8)

Dose of 1x10 E8 autologous bone marrow-derived mononuclear cells

Group Type: EXPERIMENTAL

Intraarterial infusion of autologous bone marrow cells

Intervention Type: OTHER

Autologous bone marrow-derived mononuclear cells will be infused by an intraarterial catheter into de ischemic limb. The number of infused cells will be 1x10 E8, 5x10E8 and 1x10 E9 in the low,intermediate and high dose arms respectively

Intermediate dose (5x10 E8)

Dose of 5x10 E8 autologous bone marrow-derived mononuclear cells

Group Type: EXPERIMENTAL

Intraarterial infusion of autologous bone marrow cells

Intervention Type: OTHER

Autologous bone marrow-derived mononuclear cells will be infused by an intraarterial catheter into de ischemic limb. The number of infused cells will be 1x10 E8, 5x10E8 and 1x10 E9 in the low,intermediate and high dose arms respectively

High dose (1x10 E9)

Dose of 1x10 E9 autologous bone marrow-derived mononuclear cells

Group Type: EXPERIMENTAL

Intraarterial infusion of autologous bone marrow cells

Intervention Type: OTHER

Autologous bone marrow-derived mononuclear cells will be infused by an intraarterial catheter into de ischemic limb. The number of infused cells will be 1x10 E8, 5x10E8 and 1x10 E9 in the low,intermediate and high dose arms respectively

Control

Conventional treatment established by the good clinical practice

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Intraarterial infusion of autologous bone marrow cells

Autologous bone marrow-derived mononuclear cells will be infused by an intraarterial catheter into de ischemic limb. The number of infused cells will be 1x10 E8, 5x10E8 and 1x10 E9 in the low,intermediate and high dose arms respectively

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Type 1 or 2 diabetes mellitus

2. Grade II-III Rutherford-Becker peripheral vascular disease affecting at least one limb

3. Arterial obstruction(s) located at infrapopliteal level

4. No options of endoarterial or surgical revascularization

5. Life expectancy more than 2 years

6. Unlikelihood of major amputation of the leg during the next 12 months

7. Normal analytical parameters in blood: leucocytes>3000/micoL, neutrophils>1500 microL, Hb>10mg/dl, platelets>100000 microL,AST and ALT<2.5 standard value, creatinin<2.5 mg/dl

8. Written informed consent

9. Negative pregnancy test when applicable

Exclusion Criteria

1. History of neoplasm or hematological disease

2. Uncontrolled high blood pressure (>180/110)

3. Severe cardiac insufficiency (NYHA IV) or ejection fraction<30%

4. Malignant ventricular arrythmia

5. Deep venous thrombosis during the last 3 months

6. Active bacterial infection

7. Treatment with hyperbaric oxygen, vasoactive drugs, Cox-II inhibitors or antiangiogenic agents

8. Body mass index > 40

9. Alcoholism

10. Proliferative retinopathy

11. HIV, HBV or HCV viral infection

12. Stroke or myocardial infarction during the last 3 months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iniciativa Andaluza en Terapias Avanzadas

OTHER

Sponsor Role: collaborator

Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Inmaculada Herrera, MD, PhD

Role: STUDY_CHAIR

Hospital Universitario Reina Sofia de Cordoba

Francisco Tadeo Gomez, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Virgen del Rocio

Jose Patricio Linares, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario San Cecilio

Diego Martinez, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Morales Messeguer

Vicente García, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Virgen de las Nieves

Antonio Chacon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Reina Sofía

Locations

Hospital Universitario Reina Sofia

Córdoba, , Spain

Hospital Universitario San Cecilio

Granada, , Spain

Hospital Universitario Virgen de la Nieves

Granada, , Spain

Hospital Universitario Morales Meseguer

Murcia, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Countries

Spain

Other Identifiers

2008-004064-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMMo/ICPD/2008

Identifier Type: -

Identifier Source: org_study_id