The Continuous Positive Airway Pressure Effect on Rho-associated Coiled-coil Containing Kinases Activity.

NCT ID: NCT05014529

Last Updated: 2021-09-24

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 160 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2024-12-31

Brief Summary

The ROCK (Rho-associated coiled-coil containing kinases) play a critical role in the pathogenesis of cardiovascular diseases and left ventricle hypertrophy (LVH). ROCK activity can be used as a clinical biomarker for the diagnosis and monitoring of cardiovascular disorders. Obstructive sleep apnea (OSA) increase cardiovascular disease and LVH. Continuous positive airway pressure (CPAP) is the standard therapy for OSA. This study investigate the effect of CPAP on ROCK activity and left ventricle mass.

Detailed Description

The ROCK were discovered as downstream targets of Ras homologous A and regulate various important cellular functions, including proliferation, migration, adhesion, and apoptosis. They play a critical role in the pathogenesis of cardiovascular diseases, including cardiac fibrosis, hypertrophy, and remodeling. ROCK activity can be detected in human circulating leukocytes and could potentially be used as a clinical biomarker for the diagnosis and monitoring of cardiovascular disorders. It has been proven that higher ROCK activity is present in left ventricle hypertrophy (LVH) patients than those without LVH. Obstructive sleep apnea(OSA) is characterized by recurrent collapse of the pharyngeal airway during sleep that leads to intermittent nocturnal hypoxia, resulting in a broad range of cardiovascular morbidities, including coronary artery disease, heart failure, cardiac arrhythmias, and LVH. Continuous positive airway pressure (CPAP) is the standard therapy for OSA and several studies have shown that it can effectively reduce cardiovascular disease, but the effect of CPAP on left ventricle mass reduction is still uncertain. Previous studies demonstrated that patients with OSA had higher circulatory ROCK activity than those without OSA, but the role of CPAP on ROCK activity is not known. The circulatory leukocyte ROCK activity may be used as a clinical biomarker for cardiovascular disease and ROCK inhibitors may be used in the future as a treatment. OSA and CPAP treatment may also affect ROCK activity, the relationship between CPAP treatment, cardiac hypertrophy, and ROCK activity is important and should be clarified. Therefore, the main purpose of our study is to evaluate the effect of CPAP on ROCK activity and left ventricle mass.

Conditions

Obstructive Sleep Apnea

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Control group

Polysomography show AHI less than 15 events/h and participants do not receive any intervention include CPAP, oral appliance, or surgery for 6 months.

No interventions assigned to this group

OSA without CPAP group

Polysomography show AHI greater than 15 events/h and participants do not receive any intervention include CPAP, oral appliance, or surgery for 6 months.

No interventions assigned to this group

OSA with CPAP group

Polysomography show AHI greater than 15 events/h and participants receive CPAP more than 6 months.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

● Subjects who complete a standard polysomnography study.

Exclusion Criteria

• Patients who have heart failure (as determined by clinical symptoms or signs with elevated brain natriuretic peptide and echocardiography showing structural or functional abnormalities)
• Coronary artery disease (stress electrocardiography, myocardial scintigraphy, or coronary angiography proven coronary artery lesion)
• Hypertrophic cardiomyopathy
• Known infiltrative disease e.g. amyloidosis
• Chronic kidney disease severe than stage III
• Ischemic or hemorrhagic stroke
• Central sleep apnea,
• Hypoventilation syndrome (TCO2 or artery PaCO2 exceed 50 mmHg)
• Unstable hemodynamic state
• Eastern Cooperative Oncology Group Performance Status higher than grade 2
• Pregnant women will be excluded.
• Polysomnography exam showing sleep time less than 2 hours
• Patients who receive surgery or oral appliance during the study period

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Chung-Chieh, Yu

Director of Pulmonary Medicine Division

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sleep center

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital, Keelung

Locations

Sleep center

Keelung, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Chung-Chieh Yu, MD

Role: CONTACT

terminatorchieh@yahoo.com.tw

886+22432-9292 ext. 2657

Ning-I Yang, MD

Role: CONTACT

r3675@cgmh.org.tw

886+22431-3131 ext. 6203

References

Julian L, Olson MF. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases. 2014;5:e29846. doi: 10.4161/sgtp.29846. Epub 2014 Jul 10.

Reference Type: BACKGROUND

PMID: 25010901 (View on PubMed)

Sekizuka H, Osada N, Akashi YJ. Impact of obstructive sleep apnea and hypertension on left ventricular hypertrophy in Japanese patients. Hypertens Res. 2017 May;40(5):477-482. doi: 10.1038/hr.2016.170. Epub 2016 Dec 1.

Reference Type: BACKGROUND

PMID: 27904155 (View on PubMed)

Stewart MH, Lavie CJ, Shah S, Englert J, Gilliland Y, Qamruddin S, Dinshaw H, Cash M, Ventura H, Milani R. Prognostic Implications of Left Ventricular Hypertrophy. Prog Cardiovasc Dis. 2018 Nov-Dec;61(5-6):446-455. doi: 10.1016/j.pcad.2018.11.002. Epub 2018 Nov 6.

Reference Type: BACKGROUND

PMID: 30408469 (View on PubMed)

Zhang L, Zhuang JH, Peng H, Huang J, Huang LQ, Zhao ZX. Correlation between endothelial dysfunction, Rho-associated protein kinase activity, C-reactive protein and obstructive sleep apnoea syndrome in male patients. J Int Med Res. 2012;40(6):2183-90. doi: 10.1177/030006051204000616.

Reference Type: BACKGROUND

PMID: 23321175 (View on PubMed)

Other Identifiers

202009223870

Identifier Type: -

Identifier Source: org_study_id