Connective tissue disease (CTD), an autoimmune and inflammatory disease, usually accompanied by lung interstitial/alveolar inflammation and fibrosis (so called interstitial lung disease, ILD). The prevalence and mortality rate of CTD-ILD increase in recent several years. Although the use of corticosteroids and strong immunosuppressants can improve ILD in some patients with CTD, progressive lung fibrosis which needs lung transplantation and results in respiratory failure, even with mortality is observed. Currently, stem cell therapy is a breakthrough in the treatment of CTD-ILD, and the effective therapy with stem cells for patients with ILD have been reported.
Mesenchymal stem cells (MSCs) are adult multipotent cells with self-renewal capacity, and have immunomodulatory function. By virtue of these properties, they have an ability of tissues repairing as well as regeneration, and have immunomodulatory function through an interaction with immune cells. Compared with other MSCs, adipose tissue derived-MSC (AD-MSC) are attainable by a less invasive method, grow robustly, and have a high proliferation capacity and a low immunogenicity. Recently, AD-MSC is widely employed in the field of cardiovascular diseases and autoimmune diseases without the emergence of serious adverse events. This is a Phase I/IIa, open-labelled (without placebo group) clinical trial to treat refractory or rapidly progressive ILD in 10 patients with CTD by intravenous transfusion with allogenic AD-MSC. After signing the informed consent, CTD-ILD patients will be enrolled in this trial, including pre-treatment evaluation, admission for intravenous transfusion with AD-MSC, and post-infusion follow-up. The initial 3 subjects will receive low-dose AD-MSC (1x10E6 cells/kg) infusion therapy only once; if no adverse events after 4 weeks, the next 4-7 subjects will receive AD-MSC (1x10E6 cells/kg) infusion therapy twice; if no adverse events after 4 weeks of the last infusion, the next 8-10 subjects will receive AD-MSC (1x10E6 cells/kg) infusion therapy three times. The major aims of this trial are to improve the outcome of CTD patients with refractory ILD or rapidly progressive ILD, and identify an optimal dose of the used AD-MSC
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
The initial 3 subjects will receive low-dose AD-MSC (1x10E6 cells/kg) infusion therapy only once; if no adverse events after 4 weeks, the next 4-7 subjects will receive medium-dose AD-MSC (1x10E6 cells/kg) infusion therapy twice; if no adverse events after 4 weeks of the last infusion, the next 8-10 subjects will receive high-dose AD-MSC (1x10E6 cells/kg) infusion therapy three times.
China Medical University Hospital
Taichung, Taiwan
RECRUITINGSafety profile (between the first infusion of AD-MSCs and 48 weeks after the last infusion of AD-MSCs)
1. Stable blood pressure: systolic pressure 90-120mmHg and diastolic pressure 60-80mmHg measured after resting for 10 minutes 2. Stable pulse rate: ranges 60-100/minute after resting for 10 minutes 3. Stable respiratory rate: ranges 12-20/minute after resting for 10 minutes 4. Normal body temperature 35.7℃-37.9℃. 5. Resting oxygen saturation≧90% without oxygen use. 6. Absence of AD-MSCs infusion-related serious adverse event.
Time frame: 48 weeks
Efficacy profile (between the first infusion of AD-MSCs and 48 weeks after the last infusion of AD-MSCs)
1. Change of six-minute walking distance(6MWD): Increase of 6MWD≧5% from baseline at week 12, 8% at week 24, 10% at week 48. 2. St. George's Respiratory Questionnaire: Change of score≧5% from baseline at week 12, 10% at week 24, 15% at week 48. 3. Quality of life (SF-36): Increase of score≧5% from baseline at week 12, 8% at week 24, 10% at week 48. 4. Forced vital capacity (FVC): Decrement of FVC\<5% at week 12, increment ≧5% at week 24, increment ≧10% at week 48. 5. Diffusing capacity for carbon monoxide (DLco): Decrement of DLco \<5% at week 12, increment≧5% at week 24, increment≧10% at week 48 6. The extent of ILD (interstitial lung disease) lesion in HRCT: Decrement of ILD extent≧5% at week 24, and decrement of ILD extent≧10% at week 48.
Time frame: week 48.
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