Sleep Apnea in Patients With MGUS and MM
Λέξεις-κλειδιά
Αφηρημένη
Περιγραφή
Obesity is a risk factor for the development of MM, although the mechanisms that link obesity and MM are unclear. Obesity, in turn, is closely associated with obstructive sleep apnea. Interestingly, the key risk factors for both sleep apnea and MM are overlapping (age, sex, race and body mass index). During the apnea, or cessation of normal breathing, arterial oxygen saturation falls. This can occur as often as 60 times per hour, resulting in chronic intermittent hypoxia (CIH). In preliminary studies, investigators exposed C57BL/6 mice, that are typically resistant to engraftment of malignant plasma cells to CIH, followed by injection of malignant 5TGM1 cells. With CIH, 5TGM1 cells homed to bone marrow, and engrafted and expanded, resulting in lethal disease. These mice had key features of the myeloma phenotype, including bone damage and gammopathy. Investigators explored potential mechanisms by which CIH promote MM progression by performing whole bone marrow RNASeq analysis. They found pathways relevant to angiogenesis, cell adhesion, and stromal cell development (including dendritic cells and eosinophils) to be upregulated. This is an exciting and potentially translational finding because these elements are also upregulated in the bone marrow of human myeloma patients. Investigators also found upregulation of B cell and plasma cell development and differentiation pathway, and downregulation of B-cell apoptosis pathways. Taking these preliminary findings together, the overarching hypothesis is that CIH increases oxidative stress, thereby supporting B cell maturation and changing the bone marrow stromal microenvironment to drive the progression to MM.
Ημερομηνίες
Τελευταία επαλήθευση: | 09/30/2019 |
Πρώτα υποβλήθηκε: | 09/30/2019 |
Υποβλήθηκε εκτιμώμενη εγγραφή: | 09/30/2019 |
Δημοσιεύτηκε για πρώτη φορά: | 10/02/2019 |
Υποβλήθηκε τελευταία ενημέρωση: | 09/30/2019 |
Δημοσιεύτηκε η τελευταία ενημέρωση: | 10/02/2019 |
Ημερομηνία έναρξης της πραγματικής μελέτης: | 05/22/2019 |
Εκτιμώμενη κύρια ημερομηνία ολοκλήρωσης: | 05/22/2024 |
Εκτιμώμενη ημερομηνία ολοκλήρωσης μελέτης: | 05/22/2024 |
Κατάσταση ή ασθένεια
Παρέμβαση / θεραπεία
Procedure: Bone Marrow Aspirate and Biopsy
Φάση
Ομάδες βραχιόνων
Μπράτσο | Παρέμβαση / θεραπεία |
---|---|
A. patients with MGUS and sleep apnea | |
B. patients with MGUS and no sleep apnea | |
C. patients with MM and sleep apnea | |
D. patients with MM and no sleep apnea |
Κριτήρια καταλληλότητας
Επιλέξιμες ηλικίες για μελέτη | 18 Years Προς την 18 Years |
Φύλα επιλέξιμα για μελέτη | All |
Μέθοδος δειγματοληψίας | Non-Probability Sample |
Δέχεται υγιείς εθελοντές | Ναί |
Κριτήρια | Patients diagnosed with MGUS or MM who will be receiving a bone marrow biopsy as part of their standard of care are eligible to participate in this study |
Αποτέλεσμα
Πρωτεύοντα αποτελέσματα
1. To quantify the incidence of sleep apnea and sleep disorder in patients with MGUS and MM [From study initiation up to 5 years]
2. To compare gene expression in bone marrow stroma of MGUS and MM patients, with and without sleep apnea, and following sleep apnea treatment. [From study initiation up to 5 years]