Safety and Efficacy of Autologous Bone Marrow Stem Cells for Lower Extremity Ischemia Treating

Multicentric Study of the Autologous Bone Marrow-derived Mononuclear Cells Injection for Treatment of the Patients With Critical Lower Extremity Ischemia

The purpose of this study is to determine whether autologous bone marrow-derived stem cells are effective in the treatment of lower extremity ischemia.

Study Overview

• Status: Unknown
• Conditions: Diabetic Foot; Leg Ulcer; Peripheral Vascular Disease; Gangrene; Lower Extremity Ischemia
• Intervention / Treatment: Procedure: BM-MNC injection

Detailed Description

Critical limb ischemia (CLI) is a debilitating and disabling disease. Symptoms include pain at rest, loss of tissue integrity, distal amputations and have a major impact on the quality of life. Despite recent advances in surgical vascular procedures, a large number of patients (approximately 40%) are not eligible for these revascularization procedures. New strategies for revascularization need to be explored. Besides, in some cases results of such interventions do not give desirable effect, search of new methods of treatment therefore is necessary. Recent evidence indicates that bone marrow-derived mononuclear cells (BM-MNC) are a potential new therapeutic target.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80215-901
      • Pontificia Universidade Catolica do Parana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Critical lower limb ischemia, defined as ischemic pain at rest and / or the presence of minor tissue loss, with the possibility of healing.
• Failure of conventional medical treatment and attempts to open or percutaneous revascularization before, with an observation period of two months after the last attempt at revascularization.
• Patients considered at high risk for new revascularization procedure by at least two independent observers.

Exclusion Criteria:

• Expected life span less than six months
• Large tissue loss in the ischemic limb indicating the need for limb amputation in the short term.
• Evidence of osteomyelitis in the ischemic extremity.
• Current or previous history of neoplasia.
• Unstable angina, recent stroke or other medical condition that contraindicate anesthesia for bone marrow aspiration.
• Proliferative retinopathy.
• Debilitating disease with a life span less than one year.
• Myelofibrosis, myelodysplasia or other diseases that affect the bone marrow.
• Use of alcohol in excess of twice-daily doses or history of illicit drug use.
• Need for continuous high doses of drug therapy with steroids (more than 7.5 mg/day).
• Positivity for HIV or syphilis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BM-MNC injection; Injection of autologous bone marrow-derived mononuclear cells	Procedure: BM-MNC injection; BM-MNC cells will be injected in aliquots of 1 ml at multiple regions of the leg muscles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Wound healing (wound size, wound stage) - monitoring the healing of trophic lesions	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcome classification	Improvement of symptoms, functional capacity, exercises tolerance assessed by change in Rutherford scale of CLI	3 months, 6 months
Pain and analgesics use		3 months
Quality of life outcome		3 months, 6 months
Improvement of the coronary and collateral circulation.		3 months
Survival without amputation		6 months

Collaborators and Investigators

• Sponsor: Pontifícia Universidade Católica do Paraná
• Collaborators: Hospital Sao Rafael; Fundação Araucária; Instituto de Moléstias Cardiovasculares de São José do Rio Preto, Brazil; Hospital Geral Nacional Enrique Cabrera, Cuba; Instituto de Hematología e Inmunología, Cuba

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (ACTUAL): March 1, 2017
• Study Completion (ANTICIPATED): September 1, 2018

Study Registration Dates

• First Submitted: July 10, 2013
• First Submitted That Met QC Criteria: July 16, 2013
• First Posted (ESTIMATE): July 19, 2013

Study Record Updates

• Last Update Posted (ACTUAL): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Bone marrow; Lowe extremity ischemia; Neoangiogenesis
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Skin Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Diabetic Angiopathies; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Atherosclerosis; Foot Ulcer; Diabetic Foot; Vascular Diseases; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases; Leg Ulcer; Gangrene
• Other Study ID Numbers: ICMI_ 404732/2012-7