A Pilot Study of Biomarkers in Obstructive Sleep Apnea

NCT02325687 | Completed Results

• 1 other identifier: 2014-100
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive Sleep Apnea; Arthroplasty, Replacement, Knee; Cerebrospinal Fluid; Inflammation; TNF-alpha; Interleukin-6 (IL-6); Interleukin-8 (IL-8); Interleukin-10 (IL-10); Cytokines; Neurotrophins; BDNF; Beta-NGF; Proteomic Analysis

Outcome Measures

Primary Outcomes (1)

• Serum IL-6 (Interleukin 6) Levels

  The primary outcome, the levels of 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.

  Intraoperatively - Pre-Incision

Secondary Outcomes (6)

• Serum and CSF (Cerebrospinal Fluid) Levels of the Cytokines TNF-alpha (Tumor Necrosis Factor) , IL-6, IL-8, IL-10 (Interleukin)

  Intraoperatively - Pre-Incision

• Serum and CSF Levels of the Neurotrophins BDNF, IFN-gamma (Interferon Gamma)

  Intraoperatively - Pre-Incision

• Number of Participants With Respiratory, Cardiac, and/or CNS (Central Nervous System) Complications

  Throughout hospital stay, or an average of 1 week.

• Incidence of Intraoperative Obstructive Respiratory Events

  Throughout hospital stay, or an average of 1 week.

• Levels of Blood Oxygen Saturation

  Throughout stay in the recovery unit, or an average of 1-2 days.

Study Arms (3)

Treated OSA (CPAP-compliant)

EXPERIMENTAL

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)

Untreated OSA (non-CPAP-compliant)

EXPERIMENTAL

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)

Control (No suspicion of OSA)

EXPERIMENTAL

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)

Interventions

Lumbar Puncture (Standard-of-Care) PROCEDURE

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).

Control (No suspicion of OSA); Treated OSA (CPAP-compliant); Untreated OSA (non-CPAP-compliant)

Eligibility Criteria

• Age: 50 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Related Publications (13)

• American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Practice guidelines for the perioperative management of patients with obstructive sleep apnea: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Anesthesiology. 2014 Feb;120(2):268-86. doi: 10.1097/ALN.0000000000000053. No abstract available.

  PMID: 24346178 BACKGROUND

• Aisen PS. Serum brain-derived neurotrophic factor and the risk for dementia. JAMA. 2014 Apr 23-30;311(16):1684-5. doi: 10.1001/jama.2014.3120. No abstract available.

  PMID: 24756518 BACKGROUND

• Baessler A, Nadeem R, Harvey M, Madbouly E, Younus A, Sajid H, Naseem J, Asif A, Bawaadam H. Treatment for sleep apnea by continuous positive airway pressure improves levels of inflammatory markers - a meta-analysis. J Inflamm (Lond). 2013 Mar 22;10:13. doi: 10.1186/1476-9255-10-13. eCollection 2013.

  PMID: 23518041 BACKGROUND

• Flink BJ, Rivelli SK, Cox EA, White WD, Falcone G, Vail TP, Young CC, Bolognesi MP, Krystal AD, Trzepacz PT, Moon RE, Kwatra MM. Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly. Anesthesiology. 2012 Apr;116(4):788-96. doi: 10.1097/ALN.0b013e31824b94fc.

  PMID: 22337162 BACKGROUND

• Grandi C, Tomasi CD, Fernandes K, Stertz L, Kapczinski F, Quevedo J, Dal-Pizzol F, Ritter C. Brain-derived neurotrophic factor and neuron-specific enolase, but not S100beta, levels are associated to the occurrence of delirium in intensive care unit patients. J Crit Care. 2011 Apr;26(2):133-7. doi: 10.1016/j.jcrc.2010.10.006. Epub 2010 Nov 23.

  PMID: 21106342 BACKGROUND

• Lal C, Strange C, Bachman D. Neurocognitive impairment in obstructive sleep apnea. Chest. 2012 Jun;141(6):1601-1610. doi: 10.1378/chest.11-2214.

  PMID: 22670023 BACKGROUND

• Lim DC, Pack AI. Obstructive sleep apnea and cognitive impairment: addressing the blood-brain barrier. Sleep Med Rev. 2014 Feb;18(1):35-48. doi: 10.1016/j.smrv.2012.12.003. Epub 2013 Mar 28.

  PMID: 23541562 BACKGROUND

• Nakajima K, Kohsaka S. Microglia: neuroprotective and neurotrophic cells in the central nervous system. Curr Drug Targets Cardiovasc Haematol Disord. 2004 Mar;4(1):65-84. doi: 10.2174/1568006043481284.

  PMID: 15032653 BACKGROUND

• Nadeem R, Molnar J, Madbouly EM, Nida M, Aggarwal S, Sajid H, Naseem J, Loomba R. Serum inflammatory markers in obstructive sleep apnea: a meta-analysis. J Clin Sleep Med. 2013 Oct 15;9(10):1003-12. doi: 10.5664/jcsm.3070.

  PMID: 24127144 BACKGROUND

• Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl. 2000;(60):277-90. doi: 10.1007/978-3-7091-6301-6_19.

  PMID: 11205147 BACKGROUND

• Panaree B, Chantana M, Wasana S, Chairat N. Effects of obstructive sleep apnea on serum brain-derived neurotrophic factor protein, cortisol, and lipid levels. Sleep Breath. 2011 Dec;15(4):649-56. doi: 10.1007/s11325-010-0415-7. Epub 2010 Sep 24.

  PMID: 20865453 BACKGROUND

• Yang Q, Wang Y, Feng J, Cao J, Chen B. Intermittent hypoxia from obstructive sleep apnea may cause neuronal impairment and dysfunction in central nervous system: the potential roles played by microglia. Neuropsychiatr Dis Treat. 2013;9:1077-86. doi: 10.2147/NDT.S49868. Epub 2013 Aug 5.

  PMID: 23950649 BACKGROUND

• Wang WH, He GP, Xiao XP, Gu C, Chen HY. Relationship between brain-derived neurotrophic factor and cognitive function of obstructive sleep apnea/hypopnea syndrome patients. Asian Pac J Trop Med. 2012 Nov;5(11):906-10. doi: 10.1016/S1995-7645(12)60169-2.

  PMID: 23146807 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Inflammation; Pain Insensitivity, Congenital

Interventions

Spinal Puncture; Standard of Care

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Kethy Jules-Elysee
• Organization: Hospital for Special Surgery, Anesthesiology Department

juleselyseek@hss.edu

212-606-1206

Study Officials

• Kethy M Jules-Elysee, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2014
• First Posted: December 25, 2014
• Study Start: January 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: April 21, 2020
• Results First Posted: April 21, 2020

Record last verified: 2020-04

Locations

US (1)