Statins and CPAP in Adipose Tissue of OSA

NCT ID: NCT03308578

Last Updated: 2024-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-08

Study Completion Date

2023-12-12

Brief Summary

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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

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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.

Conditions

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Sleep Apnea, Obstructive

Keywords

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Obstructive sleep apnea Adipose tissue

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Atorvastatin

Intervention Type DRUG

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 matching study drug.

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Virend Somers, MD, PhD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Virend Somers, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Countries

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United States

References

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Bock JM, Vungarala S, Sompalli S, Covassin N, Bukartyk J, Karim S, Louis ES, Wright RS, Singh P, Somers VK. High-Intensity Atorvastatin and 24-Hour Blood Pressure in Obstructive Sleep Apnea: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. Am J Hypertens. 2025 Oct 10:hpaf202. doi: 10.1093/ajh/hpaf202. Online ahead of print.

Reference Type DERIVED
PMID: 41072928 (View on PubMed)

Greenlund IM, Bock JM, Govindan N, Kantas D, Singh P, Covassin N, Somers VK. Blood Pressure and Heart Rate Response to Orthostasis in Somali Americans. J Racial Ethn Health Disparities. 2025 Mar 15:10.1007/s40615-025-02389-7. doi: 10.1007/s40615-025-02389-7. Online ahead of print.

Reference Type DERIVED
PMID: 40088388 (View on PubMed)

Greenlund I, Bock J, Govindan N, Kantas D, Singh P, Covassin N, Somers V. Blood Pressure and Heart Rate Response to Orthostasis in Somali Americans. Res Sq [Preprint]. 2024 Oct 21:rs.3.rs-4925722. doi: 10.21203/rs.3.rs-4925722/v1.

Reference Type DERIVED
PMID: 39502777 (View on PubMed)

Other Identifiers

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R01HL065176

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17-005119

Identifier Type: -

Identifier Source: org_study_id