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

Diabetic Foot Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987363
• Other study ID #: CMMo/ICPD/2008
• Secondary ID: 2008-004064-39
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 29, 2009
• Last updated: March 15, 2016
• Start date: July 2009
• Est. completion date: March 2013

Study information

• Verified date: November 2014
• Source: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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

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:

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Limb Ischemia (CLI)
• Diabetic Foot
• Ischemia

Intervention

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

Locations

Country	Name	City	State
Spain	Hospital Universitario Reina Sofia	Cordoba
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	Sevilla

Sponsors (2)

Lead Sponsor	Collaborator
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud	Iniciativa Andaluza en Terapias Avanzadas

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events		24 h, 1,3 ,6 ,9 and 12 months	Yes
Primary	AngioRNM and/or AngioTC changes		baseline and 12 months	No
Secondary	Clinically objective improvement in the ischemic limb	(Ankle/brachial index, transcutaneous oxygen pressure, degree of Rutherford-Becker, greater ulcer size and perimeter calf muscle)	1, 3, 6, 9 and 12 months	No