Statins and CPAP in Adipose Tissue of OSA

Phase 1

Completed

Conditions: Sleep Apnea, Obstructive

Interventions: Drug: Placebo oral capsule
Drug: Atorvastatin

Registration Number: NCT03308578

Lead Sponsor: Mayo Clinic

Brief Summary: This study is aimed at examining the alterations in adipose tissue in obstructive sleep apnea (OSA) patients in response to treatment with atorvastatin in continuation with standard treatment with continuous positive airway pressure (CPAP).

Detailed Description: In recent years the role adipose tissue to the development of cardiometabolic disorders has been increasingly recognized. Dysfunctional adipose tissue is an important source for systemic inflammation, AngII, and FFA, thus increasing CV risk in obese and aging populations. Even though heightened cardiovascular risk in OSA patients is acknowledged, adipose tissue from OSA patients has not been investigated.

CPAP is standard therapy for OSA, but has shown mixed results for improvement of vascular function, insulin sensitivity, and BP, and does not reduce CV events and mortality, even in patients with established CV disease. Hence, eliminating IH alone may not be sufficient to repair preexisting damage; additional adjunct strategies aimed at cellular repair may be required to reduce cardiometabolic burden and CV risk. Statins have pleiotropic effects including reducing inflammation, and improving BP. The aim of this study is to examine the longitudinal changes in the cellular and molecular composition of adipose tissue in OSA subjects in response to 6 months combination therapy of CPAP and atorvastatin. We hypothesize that the combination therapy will reduce adipose tissue cellular damage (p16INK4A+γ-H2AX dual positive cells). Also, decreases in adipose tissue cellular damage will be associated with improved cardiometabolic profile. These studies will provide pivotal insights into potential therapeutic strategies which may reduce cardiometabolic burden in OSA population.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Oral Capsule	Placebo oral capsule	Subjects randomized to this arm will receive placebo capsules matching study drug.
Atorvastatin	Atorvastatin	Subjects randomized to this arm will be started on a lower dose of atorvastatin 40 mg daily for the first 4 weeks. If they are tolerating this dose without significant problems, atorvastatin will be increased to 80 mg daily.

Primary Outcome Measures

Name	Time	Method
Changes in prevalence of dual positive p16IND4A and gamma H2AX cells in adipose tissue	Approximately 6 months	Positivity for both (p16\^IND4A and γH2AX) serves as a marker of cellular damage. Fat biopsy from the will be performed to obtain up to 1 gm of adipose tissue. These fat samples will be batched for analysis to determine the prevalence of cellular damage. Biopsy will be obtained at 3 months and 6 month follow-up.

Secondary Outcome Measures

Name	Time	Method
Changes in prevalence of phosphorylated p53 (pp53) in adipose tissue	approximately 6months	Presence of pp53 as a ratio of phospho to total p53 to access cellular damage in adipose tissue at 3 month and 6 month follow-up
Changes in vascular endothelial function	approximately 6months	Comparison of change in brachial artery diameter in response to hyperemia at 3 month and 6 month follow-up.
Changes in insulin sensitivity	approximately 6months	Changes in the measure for area under the curve for glucose and insulin as determined during oral glucose tolerance test at 3 month and 6 month.
Changes in body composition	approximately 6months	Changes in percentage body fat content at 3 month and 6 month.
Changes in 24- h mean arterial pressure	approximately 6months	Changes in ambulatory measure of blood pressure at 3 month and 6 month.