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Trial record 29 of 32 for:    Interleukin-10

A Pilot Study of Biomarkers in Obstructive Sleep Apnea (Cytokine OSA)

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ClinicalTrials.gov Identifier: NCT02325687
Recruitment Status : Completed
First Posted : December 25, 2014
Last Update Posted : May 2, 2018
Sponsor:
Information provided by (Responsible Party):
Hospital for Special Surgery, New York

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 and/or controls.

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Procedure: Lumbar Puncture (Standard-of-Care) Not Applicable

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 cardiovascular/pulmonary morbidity (Nadeem et al., 2013). In support of this, use of CPAP therapy is associated with a reduction in the levels of circulating cytokines in patients with OSA (Baessler et al, 2013). 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 relationship. Inflammation has recently been emphasized as a component of the CNS manifestations of OSA as well, including generalized cognitive deficits and post-operative delirium (Flink et al., 2012; Lal et al., 2012). It is possible that intermittent hypoxia leads to CNS inflammation/activation of microglia (as has been shown in in vitro studies; Yang et al., 2013), which, together with blood-brain barrier (BBB) breakdown (recently shown to be involved in OSA; Lim & Pack, 2014), results in elevated circulating peripheral levels of cytokines. Alternatively (or additionally), there could be direct peripheral activation of systemic macrophages as a consequence No Title Page 6 of 36 https://ecap.hss.edu/eCAP/CustomLayouts/PrintSmartForms?Project=com.webridge.entity.E... 4/15/16 of sleep deprivation and the cortisol/stress 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 (Nakajima & Kohsaka, 2004). Alterations in levels of several neurotrophins have been implicated in multiple CNS diseases. For example, in Parkinson's 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 (Nagatsu et al., 2000). BDNF has recently been shown to protect against the development of Alzheimer's disease and dementia, as well as to increase with caloric restriction and physical activity (Aisen, 2014). 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 (Grandi et al., 2011). 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 (Wang et al., 2012) and others showing no differences compared to control patients (Panaree et al., 2011). 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, i.e., 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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?
Study Start Date : January 2015
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Experimental: Treated OSA (CPAP-compliant)

Treated OSA patients will have previously been diagnosed with OSA, and are currently CPAP-compliant. CPAP compliance is defined by daily use of a CPAP machine for at least 4 hours. We will determine if patients are CPAP-compliant by looking at their medical records and pre-operative assessments, as well as directly verifying compliance with the patient.

Intervention: Lumbar Puncture (Standard-of-Care)

Procedure: Lumbar Puncture (Standard-of-Care)
All study patients will have previously consented to undergo either spinal or spinal-epidural anesthesia. Patients will undergo their planned spinal or combined spinal-epidural placement in the OR. At the time of confirmation of placement of the spinal needle (positive CSF flow), 5 mL CSF will be collected and stored. CSF will be drawn using a standard 25g or 27g needle commonly used for anesthesia. The volume of CSF removed will be replaced with 4 cc local anesthetic (1.5% mepivacaine for spinal anesthesia).

Experimental: Untreated OSA (non-CPAP-compliant)

Patients in the untreated OSA group will have previously been diagnosed with OSA, but for some reason do not use a CPAP machine every night. We will determine if patients are CPAP-compliant by looking at their medical records and pre-operative assessments, as well as directly verifying compliance with the patient.

Intervention: Lumbar Puncture (Standard-of-Care)

Procedure: Lumbar Puncture (Standard-of-Care)
All study patients will have previously consented to undergo either spinal or spinal-epidural anesthesia. Patients will undergo their planned spinal or combined spinal-epidural placement in the OR. At the time of confirmation of placement of the spinal needle (positive CSF flow), 5 mL CSF will be collected and stored. CSF will be drawn using a standard 25g or 27g needle commonly used for anesthesia. The volume of CSF removed will be replaced with 4 cc local anesthetic (1.5% mepivacaine for spinal anesthesia).

Experimental: Control (No suspicion of OSA)

Patients in the control group will not have previously been diagnosed with OSA, and are currently not at high risk. We will determine overall risk for OSA using the STOP-BANG questionnaire. Patients with a STOP-BANG score <3 are considered to have minimal risk for OSA and will be included in the control group.

Intervention: Lumbar Puncture (Standard-of-Care)

Procedure: Lumbar Puncture (Standard-of-Care)
All study patients will have previously consented to undergo either spinal or spinal-epidural anesthesia. Patients will undergo their planned spinal or combined spinal-epidural placement in the OR. At the time of confirmation of placement of the spinal needle (positive CSF flow), 5 mL CSF will be collected and stored. CSF will be drawn using a standard 25g or 27g needle commonly used for anesthesia. The volume of CSF removed will be replaced with 4 cc local anesthetic (1.5% mepivacaine for spinal anesthesia).




Primary Outcome Measures :
  1. Serum IL-6 Levels [ Time Frame: Intraoperatively - Pre-Incision ]
    The primary outcome will be the levels of the cytokine IL-6 in serum of OSA-treated, OSA-untreated and control patients presenting for knee replacement surgery with planned spinal or combined spinal-epidural anesthesia.


Secondary Outcome Measures :
  1. Serum and CSF Levels of the cytokines TNF-alpha, IL-6, IL-8, IL-10 [ Time Frame: Intraoperatively - Pre-Incision ]
    Biological samples will be analyzed for the presence and levels of particular cytokines (TNF-alpha, IL-6, IL-8, IL-10) and neurotrophins (BDNF, β-NGF).

  2. Serum and CSF Levels of the neurotrophins BDNF, beta-NGF [ Time Frame: Intraoperatively - Pre-Incision ]
    CSF will additionally be screened for the differential expression of proteins.

  3. Incidence of respiratory, cardiac, and/or CNS complications [ Time Frame: Throughout hospital stay, or an average of 1 week. ]
    We will look at the incidence of respiratory complications (hypoxia; need for respiratory intervention), cardiac complications (MI/ACS or arrhythmias) and CNS complications (delirium, TIA or CVA). Parameters will be scored for presence or absence over the entire length of stay.

  4. Incidence of intraoperative obstructive respiratory events [ Time Frame: Throughout hospital stay, or an average of 1 week. ]
    Incidences of intraoperative obstructive respiratory events will be collected perioperatively in the operating room by the anesthesiologist

  5. Levels of blood oxygen saturation [ Time Frame: Throughout stay in the recovery unit, or an average of 1-2 days. ]
    Levels of blood oxygen saturation will be measured via arterial blood gas levels. These will be drawn as standard-of-care.

  6. Length of stay in the recovery unit [ Time Frame: Throughout stay in the recovery unit, or an average of 1-2 days. ]
    Levels of blood oxygen saturation throughout the length of stay in the recovery unit will be measured via arterial blood gas levels, found in the patient's electronic medical record



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Ages Eligible for Study:   50 Years to 84 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients between the ages of 50 and 84
  • Treated and Untreated OSA Patients: Known OSA, diagnosed by polysomnography
  • Treated OSA Patients: Known CPAP prescription, dose used nightly, and compliance status
  • Controls: No suspicion for OSA, based on STOP-BANG screening score (<3)
  • Any patient presenting for knee replacement surgery with prior consent for spinal or combined spinal-epidural anesthesia

Exclusion Criteria:

  • Presence of dementia
  • Presence of cognitive disease
  • Presence of depression, anxiety, or other mood disorder(s)
  • Recent oral steroid therapy (within prior 6 months)
  • Requirement of stress-dose steroids pre-operatively
  • Autoimmune disease
  • Neurologic disease
  • Controls: Suspected OSA, either disclosed by patient, or by clinical suspicion based on STOP-BANG questionnaire (score ≥ 3)
  • Chronic renal disease
  • Chronic liver disease
  • Traumatic spinal or spinal-epidural placement (i.e., blood-contaminated CSF)
  • Alcohol abuse - defined as being diagnosed with alcohol abuse or consuming more than 2 drinks per night, on average
  • Use of NSAIDs within 7 days prior to surgery
  • Chronic benzodiazepine use (for more than one month)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02325687


Locations
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United States, New York
Hospital for Special Surgery
New York, New York, United States, 10021
Sponsors and Collaborators
Hospital for Special Surgery, New York
Investigators
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Principal Investigator: Kethy M Jules-Elysee, MD Hospital for Special Surgery, New York

Publications:

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Responsible Party: Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT02325687     History of Changes
Other Study ID Numbers: 2014-100
First Posted: December 25, 2014    Key Record Dates
Last Update Posted: May 2, 2018
Last Verified: April 2018

Keywords provided by Hospital for Special Surgery, New York:
Interleukin-10 (IL-10)
Obstructive Sleep Apnea
Arthroplasty, Replacement, Knee
Cerebrospinal Fluid
Inflammation
TNF-alpha
Interleukin-6 (IL-6)
Interleukin-8 (IL-8)
Cytokines
Neurotrophins
BDNF
Beta-NGF
Proteomic Analysis

Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases