SCAT-OSA: Statins and CPAP in Adipose Tissue of OSA

Sponsor

Mayo Clinic (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT03308578

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

79.8

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea, Obstructive	Drug: Atorvastatin Drug: Placebo oral capsule	Phase 1/Phase 2

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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Statins and CPAP in Adipose Tissue: A Randomized Clinical Trial in Obstructive Sleep Apnea

Actual Study Start Date :

Jan 8, 2018

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Atorvastatin Subjects randomized to this arm will receive 40 mg capsules, once daily dose for the first 4 weeks followed by 2X40mg capsules, once daily dose for remaining 5 months of the study
Placebo Comparator: Placebo Oral Capsule Subjects randomized to this arm will receive placebo capsules matching study drug.	Drug: Placebo oral capsule Subjects randomized to this arm will receive placebo capsules, once daily dose for the first 4 weeks followed by 2X40mg capsules, once daily dose for remaining 5 months of the study

Arm

Intervention/Treatment

Experimental: 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.

Drug: Atorvastatin

Subjects randomized to this arm will receive 40 mg capsules, once daily dose for the first 4 weeks followed by 2X40mg capsules, once daily dose for remaining 5 months of the study

Placebo Comparator: Placebo Oral Capsule

Subjects randomized to this arm will receive placebo capsules matching study drug.

Drug: Placebo oral capsule

Subjects randomized to this arm will receive placebo capsules, once daily dose for the first 4 weeks followed by 2X40mg capsules, once daily dose for remaining 5 months of the study

Outcome Measures

Primary Outcome Measures

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

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 24- h mean arterial pressure [approximately 6months]
Changes in ambulatory measure of blood pressure at 3 month and 6 month.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Participated in IRB 17-003825
Apnea hypopnea index, AHI≥15
Women of child-bearing age will be allowed to participate if they agree to use acceptable birth control during the study period.
More than 50% obstructive apneic events.
TSH levels in range of 0.3-4.2 mIU/L

Exclusion Criteria

Elevated ALT (>3 times upper normal limit)
Fasting glucose >120 mg/dL
Females planning to be pregnant in next six months will not be included in the study
Known serious or hypersensitivity to HMG-CoA reductase inhibitors.
Alcohol consumption >3 units/day