Sleep Apnea in Patients With MGUS and MM

Multiple Myeloma Clinical Trial

Official title:

Sleep Apnea in Patients With MGUS and MM

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04114084
• Other study ID #: 201807760-A
• Status: Recruiting
• Start date: May 23, 2019
• Est. completion date: May 23, 2024

Study information

• Verified date: January 2024
• Source: University of Iowa
• Contact: Melissa Bates, PhD
• Phone: 319-335-7972
• Email: melissa-bates[@]uiowa.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: May 23, 2024
• Est. primary completion date: May 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Monoclonal Gammopathy of Undetermined Significance
• Multiple Myeloma
• Paraproteinemias

Intervention

Procedure:
• Bone Marrow Aspirate and Biopsy
The aspirate sample obtained for research at the time a standard-of-care biopsy is taking place will be approximately 40cc. Bone marrow aspiration removes bone marrow fluid and cells through a needle placed into the bone. Usually this sample is taken from the back of the pelvic bone, but it may also be taken from the sternum or the front of the pelvic bone. A bone marrow biopsy removes bone with the marrow inside and is done prior to the aspirate. Each biopsy and aspirate procedure takes approximately 15 minutes total. Bone marrow aspirate may be collected in a separate tube for research or collected from the standard-of-care specimen with left-over aspirate not otherwise needed for clinical purposes, or from previous procedures.

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Melissa Bates	Department of Health and Human Services

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To quantify the incidence of sleep apnea and sleep disorder in patients with MGUS and MM		From study initiation up to 5 years
Primary	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