Clinical trial NCT00987363: Intraarterial Infusion of Autologous Bone Marrow in Diabetic Patients With Chronic Ischemia of Lower Limbs (CLI) no Revascularization
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Critical Limb Ischemia (CLI)
Diabetic Foot
Keywords: critical limb ischemia (CLI)
diabetic foot
bone marrow derived mononuclear cells
cell therapy
Lead sponsor: Andalusian Network for Design and Translation of Advanced Therapies
Sponsor class: OTHER
Collaborators: name: Iniciativa Andaluza en Terapias Avanzadas
First posted: 2009-09-30
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

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

Primary outcomes:
measure: Number of adverse events
timeFrame: 24 h, 1,3 ,6 ,9 and 12 months
measure: AngioRNM and/or AngioTC changes
timeFrame: baseline and 12 months
Secondary outcomes:
measure: Clinically objective improvement in the ischemic limb
timeFrame: 1, 3, 6, 9 and 12 months
Other outcomes:
Locations:
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio
city: Granada
country: Spain
facility: Hospital Universitario Virgen de la Nieves
city: Murcia
country: Spain
facility: Hospital Universitario Morales Meseguer
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Hospital Universitario Reina Sofia de Cordoba
name: Inmaculada Herrera, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Virgen del Rocio
name: Francisco Tadeo Gomez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario San Cecilio
name: Jose Patricio Linares, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Morales Messeguer
name: Diego Martinez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Virgen de las Nieves
name: Vicente García, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Reina Sofía
name: Antonio Chacon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: