Ignite Creation Date:
2024-05-06 @ 3:34 AM
Last Modification Date:
2024-10-26 @ 11:36 AM
Study NCT ID:
NCT02325687
Status:
COMPLETED
Last Update Posted:
2020-04-21
First Post:
2014-12-10
Brief Title:
A Pilot Study of Biomarkers in Obstructive Sleep Apnea
Sponsor:
Hospital for Special Surgery New York
Organization:
Hospital for Special Surgery New York
Study Overview
Official Title:
A Pilot Study of Biomarkers in Obstructive Sleep Apnea OSA Is There a Correlation Between Cerebrospinal Fluid and Serum Markers of Inflammation in OSA
Status:
COMPLETED
Status Verified Date:
2020-04
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:
Cytokine OSA
Brief Summary:
Obstructive sleep apnea OSA is common and is a risk factor for postoperative complications including respiratory and cardiac events and delirium Despite this risk however there are currently no accepted biomarkers that can predict poor outcomes making it unclear to see which patients will have complications after surgery and who might need prolonged monitoring or an extended hospital stay An improved understanding of the pathophysiology of OSA is required to identify potential biomarkers for outcomes after surgery as well as to develop new treatments The aim of this pilot study is to identify serum and cerebrospinal CSF biomarkers associated with obstructive sleep apnea OSA The presence of cytokines and neurotrophins will be determined and quantified in both patients with OSA and in controls The CSF samples will additionally be analyzed by proteomic methods to identify potential biomarkers with significantly different levels present in patients with and without OSA The working hypothesis is that OSA patients who are non-CPAP-compliant will have higher levels of circulating cytokines and lower levels of circulating neurotrophins in serum and CSF compared to patients who are CPAP-compliant andor controls
Detailed Description:
It is being increasingly understood that OSA represents an inflammatory state with multiple studies showing increased levels of circulating cytokines possibly providing the link between OSA and cardiovascularpulmonary morbidity In support of this use of CPAP therapy is associated with a reduction in the levels of circulating cytokines in patients with OSA Despite these data to our knowledge there are no studies that specifically examine the association between the presence of cytokines and surgical complications The present investigation may be helpful for future studies looking at this relationshipInflammation has recently been emphasized as a component of the CNS manifestations of OSA as well including generalized cognitive deficits and post-operative delirium It is possible that intermittent hypoxia leads to CNS inflammationactivation of microglia as has been shown in in vitro studies which together with blood-brain barrier BBB breakdown recently shown to be involved in OSA results in elevated circulating peripheral levels of cytokines Alternatively or additionally there could be direct peripheral activation of systemic macrophages as a consequence of sleep deprivation and the cortisolstress response to this condition In any event to date there are no studies exploring the presence or levels of cytokines in the CSF of patients with OSA In addition to the release of inflammatory cytokines activation of microglia causes the release of neuroprotective neurotrophins Alterations in levels of several neurotrophins have been implicated in multiple CNS diseases For example in Parkinsons disease there is a known elevation in cytokines with reduced circulating levels of CSF neurotrophins BDNF and NGF and this balance has been posited to underlie some of the symptoms and progression of the disease BDNF has recently been shown to protect against the development of Alzheimers disease and dementia as well as to increase with caloric restriction and physical activity
Considering OSA is associated with obesity it is possible that low BDNF may at least in part mediate some of the cognitive deficits seen in OSA Additionally low BDNF is associated with postoperative delirium in clinical studies Currently the role of neurotrophins in OSA remains underinvestigated Of all the known neurotrophins only BDNF has been studied in OSA patients and the results are conflicting with some studies suggesting reduced levels of serum BDNF and others showing no differences compared to control patients This may in part be due to the detection methods employed or small sample sizes and to date no one has investigated CSF levels of neurotrophins in this patient population Here we hypothesize that the detrimental effects of circulating cytokines in OSA may be balanced in some patients by beneficial effects exerted by neurotrophins and that this differential balance may represent 1 a tool for identifying which patients are at risk for post-operative complications in future studies ie a useful biomarker for stratifying operative risk 2 a new understanding of the pathophysiology of OSA and 3 a role for neuroprotective strategies in the management of OSA
Considering OSA is associated with obesity it is possible that low BDNF may at least in part mediate some of the cognitive deficits seen in OSA Additionally low BDNF is associated with postoperative delirium in clinical studies Currently the role of neurotrophins in OSA remains underinvestigated Of all the known neurotrophins only BDNF has been studied in OSA patients and the results are conflicting with some studies suggesting reduced levels of serum BDNF and others showing no differences compared to control patients This may in part be due to the detection methods employed or small sample sizes and to date no one has investigated CSF levels of neurotrophins in this patient population Here we hypothesize that the detrimental effects of circulating cytokines in OSA may be balanced in some patients by beneficial effects exerted by neurotrophins and that this differential balance may represent 1 a tool for identifying which patients are at risk for post-operative complications in future studies ie a useful biomarker for stratifying operative risk 2 a new understanding of the pathophysiology of OSA and 3 a role for neuroprotective strategies in the management of OSA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None