Sleep Apnea, ObstructivePhase 4NCT01699126
The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome
A Phase 4 study testing CPAP and Statin in people with Sleep Apnea, Obstructive, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sleep Apnea, Obstructive
- What is being tested?
- CPAP and Statin
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteTaiwan
- Study dates
- May 2010to Aug 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Sleep Apnea, Obstructive
- Being tested
- CPAP, Statin
- Keywords
- Obstructive Sleep Apnea, CPAP, Endothelium dysfunction, Hypertension
- Medical subject headings
- Sleep Apnea, Obstructive, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CPAPDevice
Continuous Positive Airway Pressure is the routine treatment of OSA, patients will be randomly assigned into CPAP treatment group
StatinDrug
Also called rosuvastatin
Statin is an lipid lowering medication with anti-inflammatory effect.
| Study group | Role | What they receive |
|---|---|---|
| CPAP, Hypertension | Experimental | evaluate the effect on FMD, blood pressure and inflammation after CPAP on OSA Receives: Device: CPAP |
| CPAP and statin, Hypertension | Active comparator | evaluate the effect on FMD, blood pressure and inflammation after CPAP plus statin on OSA patients Receives: Device: CPAP; Drug: Statin |
| OSA, statin, Hypertension | Active comparator | evaluate the effect on FMD, blood pressure and inflammation after statin treatment on OSA Receives: Drug: Statin |
| Placebo | No intervention | We will also measure the FMD, blood pressure and inflammation on patients with only life style modification as in all other patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flow-Mediated dilatation test(FMD)
FMD is the most sensitive physical marker of endothelial function, we measure the FMD changes after treatment
Measured: 6 months
Secondary outcomes (1)
Blood pressure
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:
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2012 (estimated)
- Study startMay 2010
- Primary completionFeb 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Sleep Apnea, ObstructiveStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- WAN-CHING Ho, M.D., Principal investigator, Taiwan Society of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01699126
- Sponsor's protocol ID
- 98-2167B
- Status last verified
- Jan 2018
- First submitted
- 30 Aug 2012
- Last updated
- 1 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Luthje L, Andreas S. Obstructive sleep apnea and coronary artery disease. Sleep Med Rev. 2008 Feb;12(1):19-31. doi: 10.1016/j.smrv.2007.08.002. Epub 2007 Nov 1.
PubMed 17936040Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009 Jan 3;373(9657):82-93. doi: 10.1016/S0140-6736(08)61622-0. Epub 2008 Dec 26.
PubMed 19101028Atkeson A, Yeh SY, Malhotra A, Jelic S. Endothelial function in obstructive sleep apnea. Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):351-62. doi: 10.1016/j.pcad.2008.08.002.
PubMed 19249441Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, Colombo PC, Basner RC, Factor P, LeJemtel TH. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation. 2008 Apr 29;117(17):2270-8. doi: 10.1161/CIRCULATIONAHA.107.741512. Epub 2008 Apr 14.
PubMed 18413499Gozal D, Kheirandish-Gozal L. Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more. Am J Respir Crit Care Med. 2008 Feb 15;177(4):369-75. doi: 10.1164/rccm.200608-1190PP. Epub 2007 Nov 1.
PubMed 17975198Gilmartin GS, Tamisier R, Curley M, Weiss JW. Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H778-85. doi: 10.1152/ajpheart.00653.2007. Epub 2008 Jun 6.
PubMed 18539753Iturriaga R, Rey S, Del Rio R. Cardiovascular and ventilatory acclimatization induced by chronic intermittent hypoxia: a role for the carotid body in the pathophysiology of sleep apnea. Biol Res. 2005;38(4):335-40. doi: 10.4067/s0716-97602005000400004.
PubMed 16579514Williams B. The year in hypertension. J Am Coll Cardiol. 2008 May 6;51(18):1803-17. doi: 10.1016/j.jacc.2008.03.010. No abstract available.
PubMed 18452788Campos-Rodriguez F. Screening for sleep apnea in patients with resistant hypertension. Am J Hypertens. 2008 Jul;21(7):728. doi: 10.1038/ajh.2008.193. No abstract available.
PubMed 18584016Haentjens P, Van Meerhaeghe A, Moscariello A, De Weerdt S, Poppe K, Dupont A, Velkeniers B. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med. 2007 Apr 23;167(8):757-64. doi: 10.1001/archinte.167.8.757.
PubMed 17452537Phillips CL, Yee B, Yang Q, Villaneuva AT, Hedner J, Berend N, Grunstein R. Effects of continuous positive airway pressure treatment and withdrawal in patients with obstructive sleep apnea on arterial stiffness and central BP. Chest. 2008 Jul;134(1):94-100. doi: 10.1378/chest.07-3121. Epub 2008 Mar 17.
PubMed 18347202
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome
- ClinicalTrials.gov ID
- NCT01699126
- Acronym / sponsor ID
- 98-2167B
- Conditions
- Sleep Apnea, Obstructive
- Keywords
- Obstructive Sleep Apnea, CPAP, Endothelium dysfunction, Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- Feb 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 3 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CPAP, Hypertension | Experimental | Device: CPAPevaluate the effect on FMD, blood pressure and inflammation after CPAP on OSA |
| CPAP and statin, Hypertension | Active comparator | Device: CPAP, Drug: Statinevaluate the effect on FMD, blood pressure and inflammation after CPAP plus statin on OSA patients |
| OSA, statin, Hypertension | Active comparator | Drug: Statinevaluate the effect on FMD, blood pressure and inflammation after statin treatment on OSA |
| Placebo | No intervention | –We will also measure the FMD, blood pressure and inflammation on patients with only life style modification as in all other patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CPAPContinuous Positive Airway Pressure is the routine treatment of OSA, patients will be randomly assigned into CPAP treatment group | Device | CPAP and statin, Hypertension, CPAP, Hypertension |
| StatinAlso: rosuvastatinStatin is an lipid lowering medication with anti-inflammatory effect. | Drug | CPAP and statin, Hypertension, OSA, statin, Hypertension |
Primary outcome
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
1 secondary outcome
Blood pressure
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2018.
- Results publication: PubMed 17936040Luthje L, Andreas S. Obstructive sleep apnea and coronary artery disease. Sleep Med Rev. 2008 Feb;12(1):19-31. doi: 10.1016/j.smrv.2007.08.002. Epub 2007 Nov 1.
- Results publication: PubMed 19101028Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009 Jan 3;373(9657):82-93. doi: 10.1016/S0140-6736(08)61622-0. Epub 2008 Dec 26.
- Results publication: PubMed 19249441Atkeson A, Yeh SY, Malhotra A, Jelic S. Endothelial function in obstructive sleep apnea. Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):351-62. doi: 10.1016/j.pcad.2008.08.002.
- Results publication: PubMed 18413499Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, Colombo PC, Basner RC, Factor P, LeJemtel TH. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation. 2008 Apr 29;117(17):2270-8. doi: 10.1161/CIRCULATIONAHA.107.741512. Epub 2008 Apr 14.
- Results publication: PubMed 17975198Gozal D, Kheirandish-Gozal L. Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more. Am J Respir Crit Care Med. 2008 Feb 15;177(4):369-75. doi: 10.1164/rccm.200608-1190PP. Epub 2007 Nov 1.
- Results publication: PubMed 18539753Gilmartin GS, Tamisier R, Curley M, Weiss JW. Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H778-85. doi: 10.1152/ajpheart.00653.2007. Epub 2008 Jun 6.
- Results publication: PubMed 16579514Iturriaga R, Rey S, Del Rio R. Cardiovascular and ventilatory acclimatization induced by chronic intermittent hypoxia: a role for the carotid body in the pathophysiology of sleep apnea. Biol Res. 2005;38(4):335-40. doi: 10.4067/s0716-97602005000400004.
- Results publication: PubMed 18452788Williams B. The year in hypertension. J Am Coll Cardiol. 2008 May 6;51(18):1803-17. doi: 10.1016/j.jacc.2008.03.010. No abstract available.
- Results publication: PubMed 18584016Campos-Rodriguez F. Screening for sleep apnea in patients with resistant hypertension. Am J Hypertens. 2008 Jul;21(7):728. doi: 10.1038/ajh.2008.193. No abstract available.
- Results publication: PubMed 17452537Haentjens P, Van Meerhaeghe A, Moscariello A, De Weerdt S, Poppe K, Dupont A, Velkeniers B. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med. 2007 Apr 23;167(8):757-64. doi: 10.1001/archinte.167.8.757.
- Results publication: PubMed 18347202Phillips CL, Yee B, Yang Q, Villaneuva AT, Hedner J, Berend N, Grunstein R. Effects of continuous positive airway pressure treatment and withdrawal in patients with obstructive sleep apnea on arterial stiffness and central BP. Chest. 2008 Jul;134(1):94-100. doi: 10.1378/chest.07-3121. Epub 2008 Mar 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
WAN-CHING Ho, M.D. principal investigator
Taiwan Society of Cardiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing CPAP and Statin in people with Sleep Apnea, Obstructive, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Flow-Mediated dilatation test(FMD) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01699126, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2018.