Sleep Apnea in Patients With MGUS and MM

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance
• Intervention / Treatment: Procedure: Bone Marrow Aspirate and Biopsy

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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Melissa Bates, PhD; Phone Number: 319-335-7972; Email: melissa-bates@uiowa.edu
• Study Contact Backup: Name: Tina Knutson; Phone Number: 319-384-5287; Email: tina-knutson@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Melissa Bates, PhD; Phone Number: 319-335-7972; Email: melissa-bates@uiowa.edu
      • Contact: Tina Knutson; Phone Number: 319-384-5287

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
A. patients with MGUS and sleep apnea	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.
B. patients with MGUS and no sleep apnea	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.
C. patients with MM and sleep apnea	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.
D. patients with MM and no sleep apnea	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To quantify the incidence of sleep apnea and sleep disorder in patients with MGUS and MM	From study initiation up to 5 years
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

Collaborators and Investigators

• Sponsor: Melissa Bates
• Collaborators: Department of Health and Human Services
• Investigators: Principal Investigator: Melissa Bates, PhD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2019
• Primary Completion (Estimated): May 23, 2024
• Study Completion (Estimated): May 23, 2024

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (Actual): October 3, 2019

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Protein Disorders; Neoplasms, Plasma Cell; Hypergammaglobulinemia; Multiple Myeloma; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
• Other Study ID Numbers: 201807760-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No