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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier:
NCT00987363
First received: September 29, 2009
Last updated: November 13, 2014
Last verified: November 2014
  Purpose

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


Condition Intervention Phase
Arterial Occlusive Disease (CLI)
Diabetic Foot
Other: Intraarterial infusion of autologous bone marrow cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial of Therapeutic Angiogenesis With Mononuclear Cells Autologous Bone Marrow in Patients With Chronic Ischemia Diabetics Critical Limb (CLI) no Revascularization.

Resource links provided by NLM:


Further study details as provided by Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud:

Primary Outcome Measures:
  • Number of adverse events [ Time Frame: 24 h, 1,3 ,6 ,9 and 12 months ] [ Designated as safety issue: Yes ]
  • Arteriographic, AngioRNM and AngioTC changes [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinically objective improvement in the ischemic limb [ Time Frame: 1, 3, 6, 9 and 12 months ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: July 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose
The dose of infused cells is 1x10 E8
Other: 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
Experimental: Intermediate dose
The dose of infused cells is 5x10 E8
Other: 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
Experimental: High dose
The dose of infused cells is 1x10 E9
Other: 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
No Intervention: Control

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 ventricular function monitoring under angiographic and echocardiographic 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:

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00987363

Locations
Spain
Hospital Universitario Reina Sofia
Cordoba, Spain, 14004
Hospital Universitario San Cecilio
Granada, Spain, 18012
Hospital Universitario Morales Meseguer
Murcia, Spain, 30008
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
Sponsors and Collaborators
Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
Investigators
Study Director: Inmaculada Herrera, MD, PhD Hospital Universitario Reina Sofia
Principal Investigator: Francisco Tadeo Gomez, MD, PhD Hospital Virgen del Rocio
Principal Investigator: Jose Patricio Linares, MD, PhD Hospital Universitario San Cecilio
Principal Investigator: Diego Martinez, MD, PhD Hospital Universitario Morales Messeguer
Principal Investigator: Antonio Chacon, MD, PhD Hospital Universitario Reina Sofia
Principal Investigator: Jose Garcia-Revillo, MD,PhD Hospital Universitario Reina Sofia
Principal Investigator: Miguel Canis, MD Hospital Universitario Reina Sofia
Principal Investigator: Pablo Gonzalez, MD Hospital Universitario San Cecilio
Principal Investigator: Salvador Oyonarte, MD CRTS Granada
Principal Investigator: Eduardo Ros, MD,PhD Hospital Universitario San Cecilio
Principal Investigator: Rafael Ros, MD,PhD Hospital Universitario San Cecilio
Principal Investigator: Magdalena Carmona, MD Hospital Universitario Virgen del Rocio
Principal Investigator: Javier Peiro, MD Hospital Universitario Virgen del Rocio
Principal Investigator: Ricardo Asensio, MD Hospital Universitario San Cecilio
  More Information

No publications provided

Responsible Party: Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT00987363     History of Changes
Other Study ID Numbers: CMMo/ICPD/2008, 2008-004064-39
Study First Received: September 29, 2009
Last Updated: November 13, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud:
critical limb ischemia (CLI)
diabetic foot
bone marrow derived mononuclear cells
cell therapy

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Diabetic Foot
Ischemia
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Diabetic Angiopathies
Diabetic Neuropathies
Endocrine System Diseases
Foot Ulcer
Leg Ulcer
Pathologic Processes
Skin Diseases
Skin Ulcer
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014