The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by Chang Gung Memorial Hospital
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

August 30, 2012
October 16, 2012
May 2010
December 2012   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01699126 on ClinicalTrials.gov Archive Site
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:

Blood pressure [ Time Frame: six 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:

  • 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.
Same as current
 
The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome
The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Sleep Apnea, Obstructive
  • 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
  • Experimental: CPAP, Hypertension
    evaluate the effect on FMD, blood pressure and inflammation after CPAP on OSA
    Intervention: Device: CPAP
  • Active Comparator: CPAP and statin, Hypertension
    evaluate the effect on FMD, blood pressure and inflammation after CPAP plus statin on OSA patients
    Interventions:
    • Device: CPAP
    • Drug: Statin
  • Active Comparator: OSA, statin, Hypertension
    evaluate the effect on FMD, blood pressure and inflammation after statin treatment on OSA
    Intervention: Drug: Statin
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
120
August 2013
December 2012   (final data collection date for primary outcome measure)

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).

Both
18 Years and older
No
Contact: WAN-CHING HO, M.D. +886-975362633 auditory@adm.cgmh.org.tw
Taiwan
 
NCT01699126
98-2167B
Yes
Chang Gung Memorial Hospital
Chang Gung Memorial Hospital
Not Provided
Principal Investigator: WAN-CHING Ho, M.D. Taiwan society of cardiology
Chang Gung Memorial Hospital
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP