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The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by Chang Gung Memorial Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01699126
First received: August 30, 2012
Last updated: October 16, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Sleep Apnea, Obstructive
Device: CPAP
Drug: Statin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • Flow-Mediated dilatation test(FMD) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    FMD is the most sensitive physical marker of endothelial function, we measure the FMD changes after treatment


Secondary Outcome Measures:
  • Blood pressure [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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:



Other Outcome Measures:
  • Hs-CRP [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Endothelial dysfunction is supposed to be mediated by inflammation process after hypoxia. Hs-CRP is the most sensitive marker to evaluate the inflammation level.

  • Inflammatory markers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Inflammation after hypoxia is suggested to be the pathogenesis of endothelial dysfunction. We will measure the inflammatory markers after treatment.


Estimated Enrollment: 120
Study Start Date: May 2010
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01699126

Contacts
Contact: WAN-CHING HO, M.D. +886-975362633 auditory@adm.cgmh.org.tw

Locations
Taiwan
Chang Gang Memorial Hospital Recruiting
Taoyuan, Taiwan, 333
Contact: WAN-CHING HO, M.D.    +886975362633    auditory@adm.cgmh.org.tw   
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
Principal Investigator: WAN-CHING Ho, M.D. Taiwan society of cardiology
  More Information

Publications:

Responsible Party: Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT01699126     History of Changes
Other Study ID Numbers: 98-2167B
Study First Received: August 30, 2012
Last Updated: October 16, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by Chang Gung Memorial Hospital:
Obstructive Sleep Apnea
CPAP
Endothelium dysfunction
Hypertension

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

ClinicalTrials.gov processed this record on November 25, 2014