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Statins and CPAP in Adipose Tissue of OSA (SCAT-OSA)

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ClinicalTrials.gov Identifier: NCT03308578
Recruitment Status : Enrolling by invitation
First Posted : October 12, 2017
Last Update Posted : January 9, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Virend Somers, 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).

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 Type : Interventional  (Clinical Trial)
Estimated 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 : January 8, 2018
Estimated Primary Completion Date : October 1, 2022
Estimated Study Completion Date : July 2023


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




Primary Outcome Measures :
  1. Changes in prevalence of dual positive p16IND4A and gamma H2AX cells in adipose tissue [ Time Frame: 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 :
  1. Changes in prevalence of phosphorylated p53 (pp53) in adipose tissue [ Time Frame: 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

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

  3. Changes in vascular endothelial function [ Time Frame: approximately 6months ]
    Comparison of change in brachial artery diameter in response to hyperemia at 3 month and 6 month follow-up.

  4. Changes in insulin sensitivity [ Time Frame: 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.

  5. Changes in body composition [ Time Frame: approximately 6months ]
    Changes in percentage body fat content at 3 month and 6 month.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03308578


Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Virend Somers, MD, PhD Mayo Clinic
Principal Investigator: Prachi Singh, Ph.D. Mayo Clinic

Responsible Party: Virend Somers, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03308578     History of Changes
Other Study ID Numbers: 17-005119
R01HL065176 ( U.S. NIH Grant/Contract )
UL1TR000135 ( U.S. NIH Grant/Contract )
First Posted: October 12, 2017    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Virend Somers, Mayo Clinic:
Obsructive sleep apnea
Adipose tissue

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Atorvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors