Cell Therapy With Mesenchymal Stem Cell in Ischemic Limb Disease

Taiwan Bio Therapeutics

Status and phase: Completed; Phase 1

Conditions: Critical Limb Ischemia

Treatments: Drug: Normal saline; Drug: Allogenic MSC

Study type: Interventional

Funder types: Industry

Identifiers

NCT02336646

2012-02-070B

Details and patient eligibility

About

Bone marrow MSCs will be isolated from allogenic donors, expanded under hypoxic conditions using medium containing no serum or animal-derived reagents, and applies for Phase Ⅰ/Ⅱ study in treating 18 recipients with ischemic limb diseases.

Full description

Ischemic limb disease remains one of the major causes of morbidity and mortality in the industrialized world despite the development of several new therapeutic modalities. Based on experimental data demonstrating that infusion or injection of stem/progenitor cells enhances blood flow in models of cardiovascular diseases, clinical trials were initiated in 2001 to treat patients with critical limb ischemia or cardiac ischemia with circulating blood or bone marrow-derived cells. Despite all promises, pending uncertainties and practical limitations attenuate the therapeutic use of stem/progenitor cells for ischemic limb disease. The main theme and method in the current program project, based on expertise, track record, and preliminary results of PI's laboratory, is to focus on clinical studies of using allogenic mesenchymal stem cells (MSCs), expanded under hypoxic conditions (1% O2), in treating ischemic limbs. This project is an integrated and coordinated effort aimed to overcome the regulation of cell product, and the barriers of preclinical and clinical studies. For the purposes, we have specially set up the core laboratory for stem/progenitor cells production and quality control in Cell Therapy Clean Room on the 9th floor of Medical Science Technology Building in Taipei Veterans General Hospital. We have also completed the preclinical studies in using allogenic hypoxic mouse MSCs in treating limb ischemia. In the current project, bone marrow MSCs will be isolated from allogenic donors, expanded under hypoxic conditions using medium containing no serum or animal-derived reagents, and applies for Phase Ⅰ/Ⅱ study in treating 18 recipients with ischemic limb diseases in three years.

Enrollment: 18 patients

Sex: All

Ages: 20 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Fontaine stage > II, total walking distance < 100 m, stair < 1 floor, or ulcer / necrosis
• Established critical limb ischemia, clinically and hemodynamically confirmed as per Rutherford- Ⅱ-4, Ⅲ-5, or Ⅲ-6; Patients having Infra-inguinal arterial occlusive disease with rest pain or ischemic ulcer/necrosis, who are not eligible for or have failed traditional revascularization treatment
• Ankle Brachial Pressure Index (ABPI) ≤ 0.8，ankle pressure ≤ 70 mm Hg, or TcPO2 ≤ 70 mmHg in the foot
• No response to medication (aspirin and cilostazol)
• Normal liver and renal function
• On regular medication for hypertension if any

Exclusion criteria

• The above mentioned patients combined with infection or systemic septicemia. (ps, patients with poor control of diabetes, hypertension and hyperlipidemia will also be excluded
• Patient with Immunocompromised or immunosuppressed
• Type I Diabetes
• Patients having stroke or myocardial infarction within last 3 months
• Hb% < 10 gm%, Serum Creatinine ≥ 2mg%, Serum Total Bilirubin ≥2mg%, HbA1c > 8%

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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18 participants in 3 patient groups, including a placebo group

Low Dose Allogenic MSC

Experimental group

Description:

Low dose allogenic mesenchymal stem cells with IM injection

Treatment:

Drug: Allogenic MSC

High Dose Allogenic MSC

Experimental group

Description:

High dose allogenic mesenchymal stem cells with IM injection

Treatment:

Drug: Allogenic MSC

Placebo

Placebo Comparator group

Description:

normal saline with Intramuscular injection

Treatment:

Drug: Normal saline