We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT01408381
Previous Study | Return to List | Next Study

Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Non-diabetic Patients With Critical Limb Ischemia (CLI).

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01408381
Recruitment Status : Completed
First Posted : August 3, 2011
Last Update Posted : March 16, 2016
Sponsor:
Collaborator:
Iniciativa Andaluza en Terapias Avanzadas
Information provided by (Responsible Party):
Andalusian Network for Design and Translation of Advanced Therapies ( Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud )

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

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

The hypothesis of the test we propose is that the mononuclear cells of bone marrow provide progenitor cells with regenerative capacity and besides secrete 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 or disease Intervention/treatment Phase
Critical Limb Ischemia (CLI) Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells Phase 2

Detailed Description:

The study population will consist of a total of 44 non-diabetic patients with chronic critical ischemia in at least one of their lower limbs (CLI) and without possibility of revascularization. In the experimental group will be included a total of 33 patients divided into three levels of dose, 11 patients in each level (increasing dose of mononuclear cells from autologous bone marrow) and other 11 patients in control group.

  • 11 patients in group 1 will not receive cell therapy, and they will only receive conventional treatment, acting as a control group.
  • 11 patients in group 2 will receive 1x108 autologous bone marrow mononuclear cells.
  • 11 patients in group 3 will receive 5x108 autologous bone marrow mononuclear cells.
  • 11 patients in group 4 will receive 1x109 autologous bone marrow mononuclear cells.

The cell therapy drug will be administered intra-arterially in all cases. Patients will be evaluated by clinical, radiological and angiological methods (ankle / brachial pressure index, transcutaneous oxygen pressure, perimeter calf muscle, presence of ulcers, oximetry and digital arteriography).

Patients will receive concomitant drug treatment established by the good clinical practice, so undoubtedly it could be possible that some improvement occurs due to drug treatment.

It is estimated that the inclusion period is approximately 42 months, and the follow-up of each patient of six months. Therefore the total duration of the study will be about forty eight months from the entry of the first patient to the end of the follow-up period of the last patient included.

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

Study objectives :

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

Secondary objectives:

  1. To compare the effect of three increasing dose of mononuclear cells from autologous bone marrow in the recovery of clinical, angiographic angiologist parameters in non-diabetic patients with critical chronic ischemia of lower limbs to a control group that will have been applied to a conventional treatment.
  2. To analyze complications from regenerative therapy itself, from the route of administration and / or study procedures.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter Phase II, Randomized Open Clinical Trial on the Therapeutic Use of Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Non-diabetic Patients With Critical Chronic Ischemia of Lower Limbs (CLI).
Study Start Date : January 2011
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
No Intervention: Control
No cell therapy
Experimental: Low dose
Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 1 x 108
 Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear 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 1x108, 5x108 and 1x109 low, intermediate and high dose in the arms respectively.
Experimental: Intermediate dose
Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 5 x 108
 Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear 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 1x108, 5x108 and 1x109 low, intermediate and high dose in the arms respectively.
Experimental: High dose
Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 1 x 109
 Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear 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 1x108, 5x108 and 1x109 low, intermediate and high dose in the arms respectively.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Adverse events [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Ankle-brachial index [ Time Frame: 1 month, 3 months, 6 months ]
  2. Transcutaneous oxygen pressure (TcO2) [ Time Frame: 1 month, 3 months, 6 months ]
  3. Greater ulcer size [ Time Frame: 1 month, 3 months, 6 months ]
    Ulcer diameter will be recorded

  4. Degree of Rutherford-Becker [ Time Frame: 1 month, 3 months, 6 months ]
  5. Perimeter calf muscle [ Time Frame: 1 month, 3 months, 6 months ]
  6. Presence of faster opacity in infrapopliteal vessels at 6 months compared with the basal situation of the patient. [ Time Frame: 1 month, 3 month, 6 month ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients of both sexes aged ≥ 18 and ≤ 89 years.
  • Non-diabetic.
  • Infrapopliteal atherosclerotic vascular disease with severe to severe claudication or Rutherford-Becker grade I-3, II, III, in at least one lower limb. The chronic critical ischemia of the lower limb is defined as persistent / recurring pain requiring analgesia and / or non-healing ulcers present> 4 weeks, with no evidence of improvement with conventional therapies and / or walking test (stress test) between 1-6 minutes two exercise tests separated by at least 2 weeks and / or ankle-brachial index at rest <0.8.
  • Inability to endovascular or surgical revascularization as recommended by the TransAtlantic Inter-Society Consensus (TASC).
  • Failure of the revascularization surgical performed at least 30 days before, either persistently or entry in critical ischemia phase.
  • Life expectancy> 2 years.
  • Not expected major amputation in the limb to treat in the next 6 months after inclusion.

  • Normal laboratory parameters, defined by:

    1. Leukocytes ≥ 3000
    2. Neutrophils ≥ 1500
    3. Platelets ≥ 100,000
    4. Aspartate aminotransferase AST) / Alanine aminotransferase (ALT) ≤ 2.5 standard range institution.
    5. Creatinine ≤ 2.5 mg / dl
  • Patients should give their written informed consent to participate in the study.
  • Women of childbearing potential must have negative results on a pregnancy test following standard procedures for each hospital performed at the time of inclusion in the study and agree to use a medically approved method of contraception through the duration of the study.

Exclusion Criteria:

  • History of malignancy or hematologic disease (myeloproliferative disease, myelodysplastic syndrome or leukemia)
  • Patients with uncontrolled hypertension (defined as blood pressure> 180/110 on more than one occasion).
  • Severe heart failure (New York Heart Association IV).
  • Patients with malignant ventricular arrhythmias or unstable angina.
  • Diagnosis of deep vein thrombosis in the previous 3 months.
  • Active infection or gangrene wet day infusion of mononuclear bone marrow cells.
  • Corporal mass index (BMI)> 40 kg/m2.
  • Patients with a diagnosis of alcoholism at the time of inclusion.
  • Proliferative retinopathy.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01408381


Locations
Layout table for location information
Spain
University Hospital Reina Sofía
Cordoba, Spain, 14004
University Hospital Puerta del Mar
Cádiz, Spain, 11009
University Hospital Virgen de las Nieves
Granada, Spain, 18014
University Hopistal Carlos Haya
Málaga, Spain, 29010
University Hospital Nuestra Señora de Valme
Sevilla, Spain, 41014
Sponsors and Collaborators
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Iniciativa Andaluza en Terapias Avanzadas
Investigators
Layout table for investigator information
Study Chair: Inmaculada Herrera, MD, PhD University Hospital Reina Sofía, Córdoba.
Principal Investigator: Antonio Chacon, MD, PhD University Hospital Reina Sofia, Córdoba
Principal Investigator: Diego Martinez, MD, PhD University Hospital Morales Meseguer, Murcia
Principal Investigator: Jose P Linares, MD, PhD University Hospital San Cecilio, Granada
Principal Investigator: Vicente Garcia, MD, PhD University Hospital Virgen de las Nieves, Granada
Principal Investigator: Andres Garcia, MD, PhD University Hospital Nuestra Señora de Valme, Sevilla
Principal Investigator: Manuel Piñero, MD, PhD University Hospital Puerta del Mar, Cádiz
Principal Investigator: Fernando Calleja, MD, PhD University Hospital Carlos Haya, Málaga
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT01408381    
Other Study ID Numbers: CMMo/ICC/2009
2009-013636-20 ( EudraCT Number )
First Posted: August 3, 2011    Key Record Dates
Last Update Posted: March 16, 2016
Last Verified: March 2016
Keywords provided by Andalusian Network for Design and Translation of Advanced Therapies ( Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud ):
Critical Limb Ischemia (CLI)
Cell Therapy
Bone marrow mononuclear cells
Additional relevant MeSH terms:
Layout table for MeSH terms
Chronic Limb-Threatening Ischemia
Ischemia
Pathologic Processes
Peripheral Arterial Disease
Atherosclerosis
Arteriosclerosis
 Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Peripheral Vascular Diseases
Chronic Disease
Disease Attributes