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

• ClinicalTrials.gov Identifier: NCT03308578
• Recruitment Status: Enrolling by invitation
• First Posted: October 12, 2017
• Last Update Posted: February 24, 2020
• Sponsor: Mayo Clinic
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Virend Somers, MD, PhD, Mayo Clinic

Tracking Information

• First Submitted Date: October 9, 2017
• First Posted Date: October 12, 2017
• Last Update Posted Date: February 24, 2020
• Actual Study Start Date: January 8, 2018
• Estimated Primary Completion Date: October 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2017)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 9, 2017)

• 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
• Changes in 24- h mean arterial pressure [ Time Frame: approximately 6months ]
  Changes in ambulatory measure of blood pressure at 3 month and 6 month.
• 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.
• 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.
• Changes in body composition [ Time Frame: approximately 6months ]
  Changes in percentage body fat content at 3 month and 6 month.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Statins and CPAP in Adipose Tissue of OSA
• Official Title: Statins and CPAP in Adipose Tissue: A Randomized Clinical Trial in Obstructive Sleep Apnea
• 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 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: 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
• 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

Study Arms

• 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.
  Intervention: Drug: Atorvastatin
• Placebo Comparator: Placebo Oral Capsule
  Subjects randomized to this arm will receive placebo capsules matching study drug.
  Intervention: Drug: Placebo oral capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: October 9, 2017): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2023
• Estimated Primary Completion Date: October 1, 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03308578
• Other Study ID Numbers: 17-005119; R01HL065176 ( U.S. NIH Grant/Contract ); UL1TR000135 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Responsible Party: Virend Somers, MD, PhD, Mayo Clinic
• Study Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Virend Somers, MD, PhD; Mayo Clinic
• Principal Investigator: Prachi Singh, Ph.D.; Mayo Clinic

• PRS Account: Mayo Clinic
• Verification Date: February 2020