Clinical trial NCT04114084: Sleep Apnea in Patients with MGUS and MM
Official title: Sleep Apnea in Patients with MGUS and MM
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Myeloma
Monoclonal Gammopathy of Undetermined Significance
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Department of Health and Human Services
First posted: 2019-10-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with MGUS or MM who will be receiving a bone marrow biopsy as part of their standard of care with and without sleep apnea

Brief summary: This study involves patients with plasma cell dyscrasia including monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM), with and without sleep apnea, who are providing bone marrow specimens. Specimens will be obtained at the time that patients undergo a standard-of-care procedure in order to minimize discomfort and reduce any risk.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To quantify the incidence of sleep apnea and sleep disorder in patients with MGUS and MM
timeFrame: From study initiation up to 5 years
measure: To compare gene expression in bone marrow stroma of MGUS and MM patients, with and without sleep apnea, and following sleep apnea treatment.
timeFrame: From study initiation up to 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
Study officials:
affiliation: University of Iowa
name: Michael Tomasson, MD
role: PRINCIPAL_INVESTIGATOR
References: