Critical Limb Ischemia
Conditions
Brief summary
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.
Detailed 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.
Interventions
DRUGAllogenic MSC
Hypoxia-cultured human bone marrow derived mesenchymal stem cells
DRUGNormal saline
Sponsors
Taiwan Bio Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 6 months | Number of adverse events reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy-The Wong Baker FACES® pain rating scale | 6 months | The Wong Baker FACES® pain rating scale, for evaluation of ischemic pain in the diseased lower limb of subjects receiving cell injection compared to placebo |
| Efficacy-Transcutaneous oxygen pressure(TcPO2) | 6 months | The Transcutaneous oxygen pressure (TcPO2) on foot of subjects receiving cell injection compared to placebo |
| Efficacy-walking distance (TWD) | 6 months | Total walking distance (TWD) on a standardized treadmill test compared to placebo |
| Efficacy-Ankle Brachial Pressure Index (ABPI) | 6 months | The Ankle Brachial Pressure Index (ABPI) in the lower limb of subjects receiving cell injection compared to placebo |
Countries
Taiwan
Outcome results
None listed