A Cross-sectional Study Examining Adipose Tissue in Obstructive Sleep Apnea

Studies show that sleep apnea increases the risk of cardiovascular disease and is associated with obesity. However, it is unclear how sleep apnea affects fat tissue. Studies have shown that fat tissue is likely involved in developing cardiovascular disease. The purpose of this study is to see how sleep apnea changes fat tissue.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea of Adult

Detailed Description

In recent years, the contribution of adipose tissue to obesity-related insulin resistance (IR), diabetes mellitus and cardiovascular disease (CVD) has become clear.In particular, accumulation of damaged cells in obese and aging adipose tissue has been shown to impair adipose tissue function and may thus increase CVD risk. Cellular and molecular alterations in adipose tissue are known to contribute to adipose tissue and systemic insulin resistance, chronic inflammation, and may lead to higher blood pressure. Importantly, any clinical consequences of adipose tissue dysfunction would be compounded by the large amount, and central metabolic role, of adipose tissue in humans. However, there is a gap in our understanding of the OSA-induced changes in the adipose tissue and its implication for development of cardiometabolic disorders.

The aim of this study is to examine the cellular and molecular composition of adipose tissue in obstructive sleep apnea (OSA) subjects in comparison to adipose tissue from healthy individuals. We hypothesize that adipose tissue from OSA subjects will have a higher accumulation of markers of cellular damage with positive p16 and γH2AX. These studies will provide pivotal insights into pathways that may be targeted to reduce cardiometabolic burden in OSA population.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Somers_CPL LAB; Phone Number: 507-255-8794; Email: CPLOSA@mayo.edu
• Study Contact Backup: Name: Virend Somers, MD., Ph.D; Phone Number: 507-255-1144; Email: somers.virend@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55901
      • Recruiting
      • Mayo Clinic
      • Contact: Somers_CPL LAB; Phone Number: 507-255-8794; Email: CPLOSA@mayo.edu
      • Contact: Virend Somers, MD, Ph.D; Phone Number: 507-255-1144; Email: somers.virend@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Subjects with obstructive sleep apnea and healthy subjects without chronic diseases and interested in participating will be enrolled in this study.

Description

Inclusion Criteria

• BMI ≤40 kg/m2
• Not a current smoker or tobacco user
• Individuals with treated hypertension, prehypertension, and dyslipidemia will be allowed to participate in the study
• On no prescription medications other than those medications used to treat asthma, seasonal or environmental allergies (such as Cetirizine, Fexofenadine, Desloratadine, Loratadine, etc), depression, acid reflux (such as antacids or proton pump inhibitors), topical skin treatment medications or shampoos, contraceptive pills, or intrauterine devices. Other medications may be allowed at the discretion of the study staff.
• Not pregnant or breast feeding and not intending to become pregnant or breast feed
• Ability to provide written informed consent
• If a subject is on aspirin or any other anti-inflammatory medication but free of known vascular disease and depending on the indication, the study doctor may ask the subject to suspend aspirin or anti-inflammatory therapy for 7 days prior to participation in the study. In the event that the subject does not stop the aspirin or other anti-inflammatory medication, they will not be able to participate in the study because of the risk of bleeding during the fat biopsy.

Exclusion Criteria

• Vulnerable study population will be excluded
• Presence of chronic kidney disease (creatinine >2.5 mg/dL) and/or active cancers
• Pregnancy
• Anemic (hemoglobin <12 g/dL for men and <11 g/dL for women)
• Smoking
• Use of chronic medications (statins, anti-inflammatory drugs, angiotensin II receptor blockers (ARBs) and/or angiotensin-converting enzyme (ACE) inhibitors)
• Blood or plasma donation during the past 2 months

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Obstructive Sleep Apnea; Obstructive sleep apnea is defined as having Apnea hypopnea index (AHI) >=5
Non-Obstructive Sleep Apnea; Non-Obstructive sleep apnea is defined as having Apnea hypopnea index (AHI) < 5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of dual positive p16^IND4A and gamma H2AX cells in adipose tissue	Positivity for both (p16^IND4A and γH2AX) serves as a marker of cellular damage. A fat biopsy from the abdomen and thigh will be performed to obtain up to 1 gm of adipose tissue from each site. These fat samples will be batched for analysis.	Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of phosphorylated p53 (pp53) in adipose tissue	Presence of pp53 as a ratio of phospho to total p53 to access cellular damage in adipose tissue.	Day 2
24- h mean arterial pressure	ambulatory measure of blood pressure in mmHg	Day 2
Vascular endothelial function	Change in Brachial artery diameter in response to hyperemia	Day 2
Insulin sensitivity	Oral glucose tolerance testing	Day 2
Body composition	Percentage body fat content	Day 1

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Virend Somers, MD., Ph.D, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2018
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 6, 2017
• First Posted (Actual): October 11, 2017

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Obstructive Sleep Apnea; Adipose Tissue
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: 17-003825; R01HL065176 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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