This is a phase I, randomized, blinded, placebo-controlled 9 subjects pilot safety run-in followed by an additional 16 randomized subjects for a total of 25 subjects. In the pilot phase subjects will be randomized into three treatment groups of allogenic mesenchymal stem cells and in the randomized phase subjects will receive either allogenic mesenchymal stem cells or matched placebo.
Idiopathic Pulmonary Fibrosis (IPF) is a progressive and debilitating lung disease characterized by interstitial fibrosis with decreasing lung volumes and pulmonary insufficiency eventually resulting in death. Patients with Idiopathic Pulmonary Fibrosis (IPF) typically present with complaints of sub acutely progressive dyspnea and non-productive cough, often accompanied by digital clubbing. Due to the insidious onset of symptoms, however, most patients are diagnosed at late stages of the disease after significant fibrosis has occurred. Physical exam is characterized by hypoxemia, "dry" inspiratory crackles on auscultation, and occasional digital clubbing (6). Pulmonary function tests (PFTs) usually reveal restrictive lung physiology with progressive decline of forced vital capacity (FVC), diffusion capacity (DLCO) and six-minute walk distances. Diagnosis is established by the pathologic finding of usual interstitial pneumonia (with sub epithelial fibroblastic foci) by open lung biopsy (7), and/or by high resolution CT (HRCT) demonstrating the characteristic findings of peripheral/basal sub pleural reticulonodular changes with fibrosis, honeycombing, and traction bronchiectasis (8, 9). The prognosis for patients with Idiopathic Pulmonary Fibrosis (IPF) is uniformly poor. The natural history of the disease is characterized by inexorable progressive decline interspersed with "exacerbations" or periods of accelerated disease which are often fatal (5). There are no FDA approved treatment options for patients with Idiopathic Pulmonary Fibrosis (IPF) and thus no standard of care. In cases of patients under the age of 60 with limited comorbid disease, lung transplant may be offered. Patients with Idiopathic Pulmonary Fibrosis (IPF) receive empiric treatment, supportive care alone, and more recently, are offered enrollment in clinical trials. The pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) is characterized by epithelial cell injury and activation with interstitial inflammation, fibroblast proliferation with extracellular matrix collagen deposition, and eventual loss of function. Because mesenchymal stem cells are known to home to sites of injury, inhibit inflammation, and contribute to epithelial tissue repair, their use has been suggested as a novel therapy for the treatment of Idiopathic Pulmonary Fibrosis (IPF).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
9
The placebo will be 25 ml of Plasma-Lyte A with 1% HSA in a Cryostore bag.
Interdisciplinary Stem Cell Institute / University of Miami
Miami, Florida, United States
To determine the safety and tolerability of intravenous allo hMSCs in patients with Idiopathic Pulmonary Fibrosis (IPF).
Safety (Primary): Incidence (one month post infusion) of any treatment-emergent serious adverse events (TE-SAEs), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities.
Time frame: One month post infusion
- To explore effects of allo hMSCs on lung function: forced vital capacity (FVC).
\- Difference in absolute decline of forced vital capacity (FVC) percent predicted.
Time frame: Participants will be followed from 12 weeks to an expected average of 60 weeks following infusion.
To explore effects of allogenic human mesenchymal stem cells on symptom related quality of life.
\- Quality of Life endpoint tools to be used include: University of California San Diego-Shortness of breath (UCSD-SOBQ), short form - 36 (SF-36), and St. George's respiratory questionnaire (SGRQ) questionnaires.
Time frame: Participants will be followed from 4 weeks to an expected average of 60 weeks following infusion.
Difference in frequency of acute exacerbations of Idiopathic Pulmonary Fibrosis (IPF)
Defined as: * New or worsened dyspnea (\<30 days). * New ground glass opacities on High Resolution CT (HRCT) superimposed on chronic findings. * New or worsened hypoxemia in the absence of other identifiable causes.
Time frame: 4 weeks following infusion
Death from any cause.
Participants will be followed for the duration of the trial, which is an expected average of 60 weeks.
Time frame: 60 weeks.
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To explore effects of allogenic human mesenchymal stem cells on lung function: Diffusing Capacity (DLCO)
\- Difference in absolute decline of Diffusing capacity (DLCO).
Time frame: Participants will be followed from 12 weeks to an expected average of 60 weeks following infusion.