Sleepiness and the Effects of CPAP on Salivary Cortisol and Alpha-Amylase Levels in Patients With Sleep Apnea

NCT01196117 | Completed Results

• 1 other identifier: 481-04
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with Obstructive Sleep Apnea Syndrome (OSAS) will evidence higher levels of salivary cortisol and alpha-amylase levels prior to use of placebo and continuous positive airway pressure (CPAP) and will evidence a decrease in these levels after consistent use of continuous positive airway pressure (CPAP) therapy as compared to placebo. Their level of sleepiness will also decrease with the use of CPAP therapy and will correlate with the levels of salivary cortisol and alpha-amylase in relation to their subjective sleepiness scale, Psychomotor Vigilance Test (PVT), and pupillometry.

Conditions

Sleep Apnea; Sleep Disordered Breathing

Keywords

automatic positive airway pressure (APAP); continuous positive airway pressure (CPAP); Salivary Cortisol; Apnea; Sleep Apnea and/or any Sleep Disordered Breathing

Outcome Measures

Primary Outcomes (2)

• Salivary Cortisol Level

  Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is \<4.2 nmol/l. Samples were collected at \~7am and \~11pm on each Day: 0, 1, 7 and 14 through a salivary swab.

  Difference between Baseline(Day 0) and Average of Day 1,7,14.

• Epworth Sleepiness Score (ESS)

  Epworth Sleepiness Score (ESS) is a scale to assess sleepiness during waking hours. The scale ranges from 0-24 with higher scores indicative of greater sleepiness.

  Difference between Baseline(Day 0) and Average of Day 1,7,14.

Secondary Outcomes (8)

• Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~7am, Day 0

  Day 0, 7am

• Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~11pm, Day 0

  Day 0, 11pm

• Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~7am, Day 1

  Day 1, 7am

• Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~11pm, Day 1

  Day 1, 11pm

• Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~ 7am, Day 7

  Day 7, 7am

Study Arms (2)

14 days of Placebo therapy, then CPAP

PLACEBO COMPARATOR

14 days of placebo therapy - use of guaifenesin with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation

Device: 14 days of placebo therapy

14 days of CPAP therapy

ACTIVE COMPARATOR

14 days of continuous positive airway pressure (CPAP) therapy with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation

Device: 14 days of CPAP therapy

Interventions

14 days of placebo therapy DEVICE

14 days of placebo therapy - use of guaifenesin with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation

Also known as: placebo arm, non-CPAP arm

14 days of Placebo therapy, then CPAP

14 days of CPAP therapy DEVICE

14 days of continuous positive airway pressure (CPAP) therapy with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation

Also known as: CPAP arm

14 days of CPAP therapy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults
• Male and female
• Between ages 18 and 90
• Undergo a Polysomnography (PSG) with evidence of any sleep disordered breathing including snoring, mild/moderate/severe sleep apnea, and/or restless legs

You may not qualify if:

• Ages 17 and under
• Pregnant women

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• ResMed: collaborator

Study Sites (1)

Froedtert West Clinics - Otolaryngology Clinc

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (48)

• Block AJ, Boysen PG, Wynne JW, Hunt LA. Sleep apnea, hypopnea and oxygen desaturation in normal subjects. A strong male predominance. N Engl J Med. 1979 Mar 8;300(10):513-7. doi: 10.1056/NEJM197903083001001.

  PMID: 216912 BACKGROUND

• Bradley TD, Phillipson EA. Pathogenesis and pathophysiology of the obstructive sleep apnea syndrome. Med Clin North Am. 1985 Nov;69(6):1169-85. doi: 10.1016/s0025-7125(16)30981-6.

  PMID: 3934481 BACKGROUND

• Sullivan CE, Issa FG. Obstructive sleep apnea. Clin Chest Med. 1985 Dec;6(4):633-50.

  PMID: 3936665 BACKGROUND

• Pasquali R, Colella P, Cirignotta F, Mondini S, Gerardi R, Buratti P, Rinaldi Ceroni A, Tartari F, Schiavina M, Melchionda N, et al. Treatment of obese patients with obstructive sleep apnea syndrome (OSAS): effect of weight loss and interference of otorhinolaryngoiatric pathology. Int J Obes. 1990 Mar;14(3):207-17.

  PMID: 2341227 BACKGROUND

• Onusko E. Diagnosing secondary hypertension. Am Fam Physician. 2003 Jan 1;67(1):67-74.

  PMID: 12537168 BACKGROUND

• Weitzman ED, Czeisler CA, Zimmerman JC, Moore-Ede MC. Biological rhythms in man: relationship of sleep-wake, cortisol, growth hormone, and temperature during temporal isolation. Adv Biochem Psychopharmacol. 1981;28:475-99. No abstract available.

  PMID: 7010946 BACKGROUND

• Wittels EH. Obesity and hormonal factors in sleep and sleep apnea. Med Clin North Am. 1985 Nov;69(6):1265-80. doi: 10.1016/s0025-7125(16)30986-5.

  PMID: 3906303 BACKGROUND

• Entzian P, Linnemann K, Schlaak M, Zabel P. Obstructive sleep apnea syndrome and circadian rhythms of hormones and cytokines. Am J Respir Crit Care Med. 1996 Mar;153(3):1080-6. doi: 10.1164/ajrccm.153.3.8630548.

  PMID: 8630548 BACKGROUND

• Bratel T, Wennlund A, Carlstrom K. Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP). Respir Med. 1999 Jan;93(1):1-7. doi: 10.1016/s0954-6111(99)90068-9.

  PMID: 10464840 BACKGROUND

• Vgontzas AN, Chrousos GP. Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders. Endocrinol Metab Clin North Am. 2002 Mar;31(1):15-36. doi: 10.1016/s0889-8529(01)00005-6.

  PMID: 12055986 BACKGROUND

• Lanfranco F, Gianotti L, Maccario M. Endocrine and metabolic alterations in obstructive sleep apnea syndrome. J Endocrinol Invest. 2003 Jun;26(6):491-2. doi: 10.1007/BF03345208. No abstract available.

  PMID: 12952359 BACKGROUND

• Grunstein RR, Handelsman DJ, Lawrence SJ, Blackwell C, Caterson ID, Sullivan CE. Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy. J Clin Endocrinol Metab. 1989 Feb;68(2):352-8. doi: 10.1210/jcem-68-2-352.

  PMID: 2493027 BACKGROUND

• Cooper BG, White JE, Ashworth LA, Alberti KG, Gibson GJ. Hormonal and metabolic profiles in subjects with obstructive sleep apnea syndrome and the acute effects of nasal continuous positive airway pressure (CPAP) treatment. Sleep. 1995 Apr;18(3):172-9.

  PMID: 7610313 BACKGROUND

• Grunstein RR, Stewart DA, Lloyd H, Akinci M, Cheng N, Sullivan CE. Acute withdrawal of nasal CPAP in obstructive sleep apnea does not cause a rise in stress hormones. Sleep. 1996 Dec;19(10):774-82. doi: 10.1093/sleep/19.10.774.

  PMID: 9085485 BACKGROUND

• Meston N, Davies RJ, Mullins R, Jenkinson C, Wass JA, Stradling JR. Endocrine effects of nasal continuous positive airway pressure in male patients with obstructive sleep apnoea. J Intern Med. 2003 Nov;254(5):447-54. doi: 10.1046/j.1365-2796.2003.01212.x.

  PMID: 14535966 BACKGROUND

• Greenberg HE, Rapoport DM, Rothenberg SA, Kanengiser LA, Norman RG, Goldring RM. Endogenous opiates modulate the postapnea ventilatory response in the obstructive sleep apnea syndrome. Am Rev Respir Dis. 1991 Jun;143(6):1282-7. doi: 10.1164/ajrccm/143.6.1282.

  PMID: 2048814 BACKGROUND

• Follenius M, Krieger J, Krauth MO, Sforza F, Brandenberger G. Obstructive sleep apnea treatment: peripheral and central effects on plasma renin activity and aldosterone. Sleep. 1991 Jun;14(3):211-7.

  PMID: 1896722 BACKGROUND

• Raff H: Salivary cortisol: a useful measurement in the diagnosis of cushing's syndrome and the evaluation of the hypothalamic-pituitary-adrenal axis. The Endocrinologist 2000; 10: 9-17

  BACKGROUND

• Laudat MH, Cerdas S, Fournier C, Guiban D, Guilhaume B, Luton JP. Salivary cortisol measurement: a practical approach to assess pituitary-adrenal function. J Clin Endocrinol Metab. 1988 Feb;66(2):343-8. doi: 10.1210/jcem-66-2-343.

  PMID: 2828410 BACKGROUND

• Papanicolaou DA, Mullen N, Kyrou I, Nieman LK. Nighttime salivary cortisol: a useful test for the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 2002 Oct;87(10):4515-21. doi: 10.1210/jc.2002-020534.

  PMID: 12364428 BACKGROUND

• Raff H, Findling JW. A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med. 2003 Jun 17;138(12):980-91. doi: 10.7326/0003-4819-138-12-200306170-00010. No abstract available.

  PMID: 12809455 BACKGROUND

• Umeda T, Hiramatsu R, Iwaoka T, Shimada T, Miura F, Sato T. Use of saliva for monitoring unbound free cortisol levels in serum. Clin Chim Acta. 1981 Mar 5;110(2-3):245-53. doi: 10.1016/0009-8981(81)90353-3.

  PMID: 6261989 BACKGROUND

• Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Salivary cortisol: a better measure of adrenal cortical function than serum cortisol. Ann Clin Biochem. 1983 Nov;20 (Pt 6):329-35. doi: 10.1177/000456328302000601.

  PMID: 6316831 BACKGROUND

• Raff H, Raff JL, Findling JW. Late-night salivary cortisol as a screening test for Cushing's syndrome. J Clin Endocrinol Metab. 1998 Aug;83(8):2681-6. doi: 10.1210/jcem.83.8.4936.

  PMID: 9709931 BACKGROUND

• Castro M, Elias PC, Martinelli CE Jr, Antonini SR, Santiago L, Moreira AC. Salivary cortisol as a tool for physiological studies and diagnostic strategies. Braz J Med Biol Res. 2000 Oct;33(10):1171-5. doi: 10.1590/s0100-879x2000001000006.

  PMID: 11004717 BACKGROUND

• Broderick JE, Arnold D, Kudielka BM, Kirschbaum C. Salivary cortisol sampling compliance: comparison of patients and healthy volunteers. Psychoneuroendocrinology. 2004 Jun;29(5):636-50. doi: 10.1016/S0306-4530(03)00093-3.

  PMID: 15041086 BACKGROUND

• Chatterton RT Jr, Vogelsong KM, Lu YC, Ellman AB, Hudgens GA. Salivary alpha-amylase as a measure of endogenous adrenergic activity. Clin Physiol. 1996 Jul;16(4):433-48. doi: 10.1111/j.1475-097x.1996.tb00731.x.

  PMID: 8842578 BACKGROUND

• Skosnik PD, Chatterton RT Jr, Swisher T, Park S. Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress. Int J Psychophysiol. 2000 Apr;36(1):59-68. doi: 10.1016/s0167-8760(99)00100-2.

  PMID: 10700623 BACKGROUND

• Nater UM, Rohleder N, Gaab J, Berger S, Jud A, Kirschbaum C, Ehlert U. Human salivary alpha-amylase reactivity in a psychosocial stress paradigm. Int J Psychophysiol. 2005 Mar;55(3):333-42. doi: 10.1016/j.ijpsycho.2004.09.009.

  PMID: 15708646 BACKGROUND

• Nater UM, La Marca R, Florin L, Koller MM, Ehlert U: The relationship between salivary alpha-amylase and plasma catecholamines. J Psychophysiol 2003; 17(3): 170 (abstract).

  BACKGROUND

• Graeber RC: Aircrew fatigue and circadian rhythmicity. In: Wiener E, Nagel DC, eds. Human Factors in Aviation. New York: Academic Press; 1987: 1-48

  BACKGROUND

• Akerstedt T. Sleepiness as a consequence of shift work. Sleep. 1988 Feb;11(1):17-34. doi: 10.1093/sleep/11.1.17.

  PMID: 3283910 BACKGROUND

• Price WJ, Holley DC. Shiftwork and safety in aviation. Occup Med. 1990 Apr-Jun;5(2):343-77.

  PMID: 2203162 BACKGROUND

• Kecklund G, Akerstedt T. Sleepiness in long distance truck driving: an ambulatory EEG study of night driving. Ergonomics. 1993 Sep;36(9):1007-17. doi: 10.1080/00140139308967973.

  PMID: 8404830 BACKGROUND

• Akerstedt T. Work hours and sleepiness. Neurophysiol Clin. 1995;25(6):367-75. doi: 10.1016/0987-7053(96)84910-0.

  PMID: 8904199 BACKGROUND

• Mitler MM, Miller JC, Lipsitz JJ, Walsh JK, Wylie CD. The sleep of long-haul truck drivers. N Engl J Med. 1997 Sep 11;337(11):755-61. doi: 10.1056/NEJM199709113371106.

  PMID: 9287232 BACKGROUND

• Ohayon MM, Caulet M, Philip P, Guilleminault C, Priest RG. How sleep and mental disorders are related to complaints of daytime sleepiness. Arch Intern Med. 1997 Dec 8-22;157(22):2645-52.

  PMID: 9531234 BACKGROUND

• Hoddes E, Zarcone V, Smythe H, Phillips R, Dement WC. Quantification of sleepiness: a new approach. Psychophysiology. 1973 Jul;10(4):431-6. doi: 10.1111/j.1469-8986.1973.tb00801.x. No abstract available.

  PMID: 4719486 BACKGROUND

• Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5. doi: 10.1093/sleep/14.6.540.

  PMID: 1798888 BACKGROUND

• Chervin RD, Aldrich MS, Pickett R, Guilleminault C. Comparison of the results of the Epworth Sleepiness Scale and the Multiple Sleep Latency Test. J Psychosom Res. 1997 Feb;42(2):145-55. doi: 10.1016/s0022-3999(96)00239-5.

  PMID: 9076642 BACKGROUND

• Jokinen T, Salmi T, Ylikoski A, Partinen M. Use of computerized visual performance test in assessing day-time vigilance in patients with sleep apneas and restless sleep. Int J Clin Monit Comput. 1995;12(4):225-30. doi: 10.1007/BF01207203.

  PMID: 8820329 BACKGROUND

• Loh S, Lamond N, Dorrian J, Roach G, Dawson D. The validity of psychomotor vigilance tasks of less than 10-minute duration. Behav Res Methods Instrum Comput. 2004 May;36(2):339-46. doi: 10.3758/bf03195580.

  PMID: 15354700 BACKGROUND

• Lowenstein O, Feinberg R, Loewenfeld ID: Pupillary movements during acute and chronic fatigue. Investigative Ophthalmolog 1963; 2: 138-157

  BACKGROUND

• Yoss RE, Moyer NJ, Ogle KN. The pupillogram and narcolepsy. A method to measure decreased levels of wakefulness. Neurology. 1969 Oct;19(10):921-8. doi: 10.1212/wnl.19.10.921. No abstract available.

  PMID: 5387594 BACKGROUND

• Ludtke H, Wilhelm B, Adler M, Schaeffel F, Wilhelm H. Mathematical procedures in data recording and processing of pupillary fatigue waves. Vision Res. 1998 Oct;38(19):2889-96. doi: 10.1016/s0042-6989(98)00081-9.

  PMID: 9797985 BACKGROUND

• Merrit SL, Schnyders HC, Mercer P: Circadian aspects of papillary unrest reflecting daytime sleepiness. Sleep Research Online 1999; 2(Sup 1): 773

  BACKGROUND

• Merrit SL, Schnyders HC, Mercer P, Zhou X: The sensitivity of pupillography to circadian aspects of sleepiness. J Sleep Research 1998; 7(Sup 2): 176

  BACKGROUND

• Raff H, Ettema SL, Eastwood DC, Woodson BT. Salivary cortisol in obstructive sleep apnea: the effect of CPAP. Endocrine. 2011 Aug;40(1):137-9. doi: 10.1007/s12020-011-9474-1. Epub 2011 Apr 26. No abstract available.

  PMID: 21519909 DERIVED

MeSH Terms

Conditions

Sleep Apnea Syndromes; Apnea

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The limitation of this trial is the results were entered strictly from a manuscript published in 2011. Despite repeated attempts to reach out, the original study team members, statisticians and data are no longer available.

Results Point of Contact

• Title: B. Tucker Woodson
• Organization: Medical College of Wisconsin

bwoodson@mcw.edu

414-805-7667

Study Officials

• Hersel Raff, PhD

  Medical College of Wisconsin

  STUDY CHAIR

• Sandra L Ettema, MD, PhD

  Medical College of Wisconsin

  STUDY CHAIR

• Laura Brusky, MD

  Medical College of Wisconsin

  STUDY CHAIR

• B Tucker Woodson, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 8, 2010
• Study Start: November 15, 2004
• Primary Completion: December 15, 2011
• Study Completion: December 15, 2011
• Last Updated: April 1, 2020
• Results First Posted: April 1, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)