The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome

January 30, 2018 updated by: Chang Gung Memorial Hospital
study Hypothesis: We hypothesize that CPAP could effectively improve the endothelial dysfunction by anti-inflammatory effect in patients of OSA,and compare to the effect of statin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Obstructive sleep apnea is a prevalent disorder that affect 2-4% adults in general population. Cardiovascular and Neurocognitive complication were the most common and severe consequence noted in patients of OSA. Endothelial dysfunction is the early pathologic changes in the vascular wall that precede to the clinical cardiovascular events. Endothelial dysfunction with the deficit of vascular relaxation will induce the development of hypertension. Endothelial dysfunction predict the occurrence of ischemic heart disease and cardiovascular events as stroke. The development of endothelial dysfunction significantly remark the early sign of the development of cardiovascular diseases.

Inflammation trigger by oxygen radical in the vascular system were the major pathogenesis of the endothelial dysfunction. Intermittent hypoxia in the patients of OSA during repeated apnea at night will increase the oxygen radicals therefore trigger the cascade of inflammation process. The inflammatory process could be mediated by the activation of the transcription factors such as NF-KB, AP-1 or from the pathway of HIF-1 cascade. Inflammatory cytokine such as HsCRP inducted by the activation of NF-KB and AP-1 will induce the interaction of monocytes and lymphocytes to further injury to the endothelium of vascular wall. TGF-B secreted by lymphocyte will create the remodeling by fibroblast which result in the thickening of vascular wall. Another pathway by VEGF, endothelin 1, or other protein modulated by HIF-1 is also proposed directly injure to the endothelium that cause the following cardiovascular events.

CPAP treatment for OSA were shown to lowering the severity of blood pressure and cardiovascular events in some reports. Although the effect for blood pressure lowering is still controversial, Most reports actually showed marginal effect on reducing BP to 2 mmHg by CPAP. There is still part of OSA patients with hypertension not responding to CPAP treatment.Besides of the effect of CPAP treatment, the compliance of CPAP is still a major concerning in the treatment of OSA. 60% of patients were reported to continue used CPAP in the well-supported sleep center in USA. Even the CPAP is covered by reimbursement in USA, the low compliance of CPAP impede the treatment of cardiovascular complication of OSA. To improve the control of the cardiovascular consequence of OSA, a convenient and well-tolerated intervention is mandatory. Statin, a powerful lipid-lowering medication, is found to have a significant anti-inflammatory effect in several reports. Statin is even suggested in the population of normal cholesterol to prevent the development of cardiovascular event. Statins exert cholesterol-independent, anti-inflammatory and immunomodulatory effects. Pleiotropic effects are typically mediated by HMG-CoA reductase inhibition, are dose dependent and occur rapidly after initiation of statin treatment. In order to evaluate and explore a safe and convenient method in the control of the cardiovascular complication of OSA, we conduct this study.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taoyuan, Taiwan, 333
        • Chang Gang Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

- 1.OSA with AHI>30 2.Male patients with hypertension 3.LDL over 130 mg/dL without any lipid-lowering drug therapy in recent 6 months 4.Signed inform consent and cooperative

Exclusion Criteria:

- 1.Non-cooperative 2.Can't sign inform consent. 3.Had proven major cardiovascular complication such as AMI, CVA. 4.Major chronic disorders and inflammatory disorders: such as DM, ESRD, COPD or rheumatoid arthritis. 5.Under anti-inflammatory medication: such as aspirin, NSAID, steroids, theophylline etc. 6.Acute of chronic infection 1 weeks between blood drawing period will be discarded 7.Study medication will be discontinued among subjects who develop myopathy (CK ≥10 times ULN and muscle aches or weakness) or a persistent elevation in ALT (≥3 times ULN on 2 consecutive tests).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CPAP, Hypertension
evaluate the effect on FMD, blood pressure and inflammation after CPAP on OSA
Device: CPAP
Continuous Positive Airway Pressure is the routine treatment of OSA, patients will be randomly assigned into CPAP treatment group
Active Comparator: CPAP and statin, Hypertension
evaluate the effect on FMD, blood pressure and inflammation after CPAP plus statin on OSA patients
Device: CPAP
Continuous Positive Airway Pressure is the routine treatment of OSA, patients will be randomly assigned into CPAP treatment group
Drug: Statin
Statin is an lipid lowering medication with anti-inflammatory effect.
Other Names:
  • rosuvastatin
Active Comparator: OSA, statin, Hypertension
evaluate the effect on FMD, blood pressure and inflammation after statin treatment on OSA
Drug: Statin
Statin is an lipid lowering medication with anti-inflammatory effect.
Other Names:
  • rosuvastatin
No Intervention: Placebo
We will also measure the FMD, blood pressure and inflammation on patients with only life style modification as in all other patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Flow-Mediated dilatation test(FMD)
Time Frame: 6 months
FMD is the most sensitive physical marker of endothelial function, we measure the FMD changes after treatment
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood pressure
Time Frame: 6 months

Hypertension is the most common cardiovascular disease and prevalent in general population. Many factors including age, obesity, DM, atherosclerosis, OSA….etc will trigger hypertension and exacerbate disease condition. There are more and more evidences showing that OSA play an independent role in hypertension therapy.OSA with CPAP therapy had been proved to reduce blood pressure in many papers especially in resisted hypertension.

However, during OSA therapy, we found that not all OSA patients with CPAP therapy will achieve the additional goal of blood pressure reduction. Therefore, we hypothesize that there is responder and non-responder in OSA patients with hypertension to CPAP therapy. To clarify the character of responder of OSA patients with hypertension and further investigate the mechanism between OSA and hypertension, we aim to conduct this study:
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hs-CRP
Time Frame: 6 months
Endothelial dysfunction is supposed to be mediated by inflammation process after hypoxia. Hs-CRP is the most sensitive marker to evaluate the inflammation level.
6 months
Inflammatory markers
Time Frame: 6 months
Inflammation after hypoxia is suggested to be the pathogenesis of endothelial dysfunction. We will measure the inflammatory markers after treatment.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chang Gung Memorial Hospital

Investigators

  • Principal Investigator: WAN-CHING Ho, M.D., Taiwan Society of Cardiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

August 30, 2012

First Submitted That Met QC Criteria

October 1, 2012

First Posted (Estimate)

October 3, 2012

Study Record Updates

Last Update Posted (Actual)

February 1, 2018

Last Update Submitted That Met QC Criteria

January 30, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98-2167B

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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