Statins and CPAP in Adipose Tissue of OSA

Sleep Apnea, Obstructive Clinical Trial

— SCAT-OSA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03308578
• Other study ID #: 17-005119
• Secondary ID: R01HL065176
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 8, 2018
• Est. completion date: December 12, 2023

Study information

• Verified date: January 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 12, 2023
• Est. primary completion date: December 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Participated in IRB 17-003825

• Apnea hypopnea index, AHI/RDI =10, or AHI/RDI >5 with significant nocturnal hypoxemia documented by a fall in oxygen saturation to 90% or below.

• Women of child-bearing age will be allowed to participate if they agree to use acceptable birth control during the study period.

• TSH levels in range of 0.3-6 mIU/L (TSH above 6 mIU/L will be allowed if free thyroxine (free T4) is within normal range)

Exclusion Criteria

• Elevated ALT (>3 times upper normal limit)

• Fasting glucose >120 mg/dL and/or HbA1c = 6.5 %

• 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

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

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 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

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in prevalence of dual positive p16IND4A and gamma H2AX cells in adipose tissue	Positivity for both (p16^IND4A and ?H2AX) 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.	Approximately 6 months
Secondary	Changes in 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 at 3 month and 6 month follow-up	approximately 6months
Secondary	Changes in 24- h mean arterial pressure	Changes in ambulatory measure of blood pressure at 3 month and 6 month.	approximately 6months
Secondary	Changes in vascular endothelial function	Comparison of change in brachial artery diameter in response to hyperemia at 3 month and 6 month follow-up.	approximately 6months
Secondary	Changes in insulin sensitivity	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.	approximately 6months
Secondary	Changes in body composition	Changes in percentage body fat content at 3 month and 6 month.	approximately 6months

External Links

•   Mayo Clinic Clinical Trials