Cell Therapy With Mesenchymal Stem Cell in Ischemic Limb Disease

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.

Study Overview

• Status: Completed
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Drug: Normal saline; Drug: Allogenic MSC

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low Dose Allogenic MSC; Low dose allogenic mesenchymal stem cells with IM injection	Drug: Allogenic MSC; Hypoxia-cultured human bone marrow derived mesenchymal stem cells; Other Names: Biochymal
EXPERIMENTAL: High Dose Allogenic MSC; High dose allogenic mesenchymal stem cells with IM injection	Drug: Allogenic MSC; Hypoxia-cultured human bone marrow derived mesenchymal stem cells; Other Names: Biochymal
PLACEBO_COMPARATOR: Placebo; normal saline with Intramuscular injection	Drug: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of adverse events reported	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy-The Wong Baker FACES® pain rating scale	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	6 months
Efficacy-Transcutaneous oxygen pressure(TcPO2)	The Transcutaneous oxygen pressure (TcPO2) on foot of subjects receiving cell injection compared to placebo	6 months
Efficacy-walking distance (TWD)	Total walking distance (TWD) on a standardized treadmill test compared to placebo	6 months
Efficacy-Ankle Brachial Pressure Index (ABPI)	The Ankle Brachial Pressure Index (ABPI) in the lower limb of subjects receiving cell injection compared to placebo	6 months

Collaborators and Investigators

• Sponsor: Taiwan Bio Therapeutics Co., Ltd.
• Investigators: Principal Investigator: Chun Che Shih, Taipei Veterans General Hospital, Taipei, Taiwan

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2015
• Primary Completion (ACTUAL): April 27, 2018
• Study Completion (ACTUAL): December 20, 2018

Study Registration Dates

• First Submitted: January 8, 2015
• First Submitted That Met QC Criteria: January 12, 2015
• First Posted (ESTIMATE): January 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 19, 2021
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: 2012-02-070B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No