Stem Cell Study for Patients With Leg Ulcer/Gangrene - Full Text View

Purpose

The purpose of this study is to determine if stem cell therapy with one's own cells (autologous cells) delivered intramuscularly to one's leg with ulcer and/or gangrene due to poor blood flow will be safe and if it will relieve leg pain, increase blood flow, and/or cure the leg wound.

Condition	Intervention	Phase
Leg Pain Ulcer Gangrene Ischemia Peripheral Vascular Diseases	Genetic: Autologous peripheral blood CD34 positive cell therapy	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I / II Clinical Trial Regarding Vascular Regeneration Therapy by Transplantation of Autologous Peripheral Blood Endothelial Progenitor Cells (CD34+ Cells) in No-Option Patients With Chronic Critical Limb Ischemia

Resource links provided by NLM:

MedlinePlus related topics: Gangrene Leg Injuries and Disorders Peripheral Arterial Disease Vascular Diseases

U.S. FDA Resources

Further study details as provided by Translational Research Informatics Center, Kobe, Hyogo, Japan:

Primary Outcome Measures:

Major amputation

Secondary Outcome Measures:

Limb ischemia

Enrollment:	15
Study Start Date:	November 2003
Study Completion Date:	January 2008

Detailed Description:

Chronic critical limb ischemia (CLI) is a progressive disease, which arises as a result of atherosclerosis or vasculitis in leg arteries. Prognosis of chronic CLI is poor, and no effective treatments have been established in patients who are not eligible for the traditional revascularization therapies such as angioplasty and bypass procedures due to the inappropriate anatomy of the leg arteries or frequent reocclusion following revascularization. Therefore, it is necessary to establish novel revascularization treatment to improve prognosis of the no-option patients. We will study the safety and clinical efficiency of vascular regeneration by means of transplantation of autologous peripheral blood endothelial progenitor cells (CD34 positive cells) in patients with chronic CLI who are not eligible for traditional revascularization treatments. The primary endpoint is the primary efficacy score identified by toe brachial blood pressure index (TBPI), absolute claudication distance (ACD) and Wong Baker's pain rating scale, while the secondary endpoints are evaluation of safety, ankle brachial blood pressure index (ABPI), percutaneous tissue oxygen pressure (TcPO2), etc.

Eligibility

Ages Eligible for Study:	20 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Chronic severe CLI patients fulfilling all the following criteria are considered suitable for inclusion in the study.
1. At least 6 months since the onset of CLI (Chronic peripheral artery disease or Buerger disease)
2. Patients with luminal stenosis > 50% by leg angiography
3. Age is between 20 and 80.
4. Patients whose Rutherford's class is II-4, III-5, or III-6（Patients with rest pain or ischemic ulcer/necrosis)
5. Patients for whom angioplasty and bypass surgery are not indicated because of anatomical or procedural reasons or frequent reocclusion/ restenosis following the traditional revascularization (No option patients)
6. Patients who can give informed consent themselves in writing.

Exclusion Criteria:

Any one of the following exclusion criteria is sufficient to disqualify a patient from the study.
1. Left ventricular ejection fraction < 25%
2. Patients with a history of severe allergic reactions or side effects to G-CSF preparations or apheresis.
3. Less than 6 months since last episode of myocardial/cerebral infarction.
4. Patients with unstable angina, with a treatment rating of 3 in the Braunwald system, but a severity of III and a clinical rating of B or C.
5. Patients with diabetic proliferating retinopathy (new Fukuda classification BI to BV).
6. Patients with malignant tumor
7. Patients with chronic rheumatoid arthritis.
8. Patients with hematological disease (leukemia, myeloproliferative disease, or myelodysplastic syndromes).
9. Patients currently suffering from or having a history of interstitial pneumonitis.
10. Patients for whom cranial MRA reveals cerebral aneurysm.
11. Patients for whom abdominal CT or ultrasonography reveals splenomegaly.
12. Patients with cirrhosis of the liver.
13. Patients who cannot discontinue Warfarin.
14. Leukocytes less than 4,000/µL or exceeding 10,000/µL.
15. Platelets less than 100,000/µL.
16. Hemoglobin less than 10 g/dL.
17. AST (GOT) exceeding 100 IU/L or ALT (GPT) exceeding 100 IU/L.
18. Patients with severe neural disorder in their legs.
19. Patients with gait disturbance for reasons other than CLI (such as sciatic neuralgia, or vasculitis), making exercise tolerance evaluation on a treadmill with stress ECG difficult.
20. Pregnant or nursing patients, those who may be pregnant, or those who plan on becoming pregnant before the end of the study period.
21. Any other reason that the Clinical Supervisors or Clinical Researchers may have for considering a case unsuitable for the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00221143

Locations

Japan
Institute of Biomedical Research and Innovation
Kobe, Hyogo, Japan, 650-0047
Kobe City General Hospital
Kobe, Hyogo, Japan, 650-0046

Sponsors and Collaborators

Translational Research Informatics Center, Kobe, Hyogo, Japan

Institute of Biomedical Research and Innovation, Kobe,Hyogo, Japan

Kobe City General Hospital

Investigators

Principal Investigator:

Takayuki Asahara, M.D.

Kobe Institute of Biomedical Research and Innovation

More Information

Additional Information:

Foundation for Biomedical Research and Innovation, Kobe, Japan This link exits the ClinicalTrials.gov site

Publications:

Asahara T, Kawamoto A. Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol. 2004 Sep;287(3):C572-9. Review.

Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C, Uchida S, Masuo O, Iwaguro H, Ma H, Hanley A, Silver M, Kearney M, Losordo DW, Isner JM, Asahara T. Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation. 2003 Jan 28;107(3):461-8.

Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, Asahara T. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation. 2001 Feb 6;103(5):634-7.

Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997 Feb 14;275(5302):964-7.

Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999 Apr;5(4):434-8.

Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3422-7.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kinoshita M, Fujita Y, Katayama M, Baba R, Shibakawa M, Yoshikawa K, Katakami N, Furukawa Y, Tsukie T, Nagano T, Kurimoto Y, Yamasaki K, Handa N, Okada Y, Kuronaka K, Nagata Y, Matsubara Y, Fukushima M, Asahara T, Kawamoto A. Long-term clinical outcome after intramuscular transplantation of granulocyte colony stimulating factor-mobilized CD34 positive cells in patients with critical limb ischemia. Atherosclerosis. 2012 Oct;224(2):440-5. doi: 10.1016/j.atherosclerosis.2012.07.031. Epub 2012 Jul 27.

Kawamoto A, Katayama M, Handa N, Kinoshita M, Takano H, Horii M, Sadamoto K, Yokoyama A, Yamanaka T, Onodera R, Kuroda A, Baba R, Kaneko Y, Tsukie T, Kurimoto Y, Okada Y, Kihara Y, Morioka S, Fukushima M, Asahara T. Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial. Stem Cells. 2009 Nov;27(11):2857-64.

Responsible Party:	Atsuhiko Kawamoto, MD, PhD Senior Research Scientist, Stem Cell Translational research Team, Institute of Biomedical Research and Innovation
ClinicalTrials.gov Identifier:	NCT00221143 History of Changes
Other Study ID Numbers:	BRI ASO 03-01
Study First Received:	September 13, 2005
Last Updated:	February 6, 2009
Health Authority:	Japan: Foundation for Biomedical Research and Innovation

Keywords provided by Translational Research Informatics Center, Kobe, Hyogo, Japan:

Ulcer/ gangrene
Leg diseases
Pain

Vascular diseases
Chronic limb ischemia
Peripheral artery disease

Additional relevant MeSH terms:

Gangrene
Ischemia
Ulcer
Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease

Necrosis
Pathologic Processes
Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases

ClinicalTrials.gov processed this record on May 16, 2013