Ignite Creation Date:
2024-05-06 @ 9:59 AM
Last Modification Date:
2024-10-26 @ 12:22 PM
Study NCT ID:
NCT03122639
Status:
COMPLETED
Last Update Posted:
2023-10-18
First Post:
2017-04-12
Brief Title:
Endothelial Function in Obstructive Sleep Apnea
Sponsor:
Columbia University
Organization:
Columbia University
Study Overview
Official Title:
Vascular Endothelial Activation in Obstructive Sleep Apnea
Status:
COMPLETED
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Obstructive sleep apnea OSA a condition that affects a quarter of the Western adults triples the risk for cardiovascular diseases and increases all-cause mortality Intermittent hypoxia IH during transient cessation of breathing in OSA leads to endothelial inflammation a key step in the initiation and progression of cardiovascular disease However the mechanisms that mediate IH-induced endothelial inflammation remain unclear and consequently no targeted therapy is available for vascular manifestations of OSA Using endothelial cells ECs freshly harvested from OSA patients they study team has identified impaired complement inhibition as an initial stimulus for endothelial inflammation in IH thereby linking for the first time complement activation to vascular risk in OSA The investigators found that a major complement inhibitor cluster of differentiation CD59 a plasma membrane protein that inhibits the formation of the terminal complement membrane attack complex MAC and protects host cells from complement injury is internalized from the EC surface in OSA patients Consequent MAC deposition initiates endothelial inflammation in IH Importantly the investigators showed that IH does not significantly affect inflammation in ECs in the absence of complement suggesting that complement activation has an essential role in endothelial inflammation in OSA Interestingly internalization of CD59 in IH appears to be cholesterol-dependent and statins prevent MAC deposition on ECs in IH in a CD59-dependent manner suggesting a novel therapeutic strategy to reduce vascular risk in OSA This led the study team to hypothesize that IH-induced cellular cholesterol accumulation reduces complement inhibition via increased internalization of CD59 from the EC surface leading to increased MAC deposition and that treatment of OSA with continuous positive airway pressure CPAP andor statins reverses endothelial dysfunction by restoring complement inhibition
Detailed Description:
To address the hypothesis the investigators seek to determine whether statins prevent endothelial dysfunction in OSA by restoring complement inhibition The preliminary data indicate that the expression of CD59 on the EC surface is preserved in OSA patients who are receiving statins and that statins prevent CD59 internalization and MAC deposition in IH leading to reduced inflammation The study proposes to determine whether statins restore endothelial protection against complement activity in OSA patients using double-blind placebo-controlled parallel group randomized study design The hypothesis The proportion of CD59 on the EC surface is increased while MAC deposition is decreased after 4 weeks of atorvastatin 10 mg daily compared with placebo in OSA patients who adhere with CPAP or do not adhere with CPAP
The proposed studies may advance our understanding of vascular dysfunction in OSA and provide the basis for large long-term clinical trials of novel therapeutic strategies such as addition of statins to the standard CPAP therapy for preventing andor reversing vascular risk in OSA
The proposed studies may advance our understanding of vascular dysfunction in OSA and provide the basis for large long-term clinical trials of novel therapeutic strategies such as addition of statins to the standard CPAP therapy for preventing andor reversing vascular risk in OSA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2R01HL106041-06A1 | NIH | None | httpsreporternihgovquickSearch2R01HL106041-06A1 |