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

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Completed
• CT.gov ID: NCT01196117
• Collaborator: ResMed (Industry)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 85
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea; Sleep Disordered Breathing	Device: 14 days of placebo therapy; Device: 14 days of CPAP therapy	N/A

Detailed Description

It has been shown that there is an inconsistent response in serum cortisol levels in patients with Obstructive Sleep Apnea Syndrome (OSAS), but it is undetermined whether a change in hormone level was not seen due to compliance issues in these long-term studies. These investigators will be employing compliance monitoring continuous positive airway pressure (CPAP) machines and also assessing "sleepiness" before and after therapy. Sleepiness is the dependent variable in our study and will be measured subjectively using sleepiness scales and objectively using Psychomotor Vigilance Test (PVT) and an autonomic measure using pupillometry prior, during and after treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Sleepiness and the Effects of CPAP on Salivary Cortisol and Alpha-Amylase Levels in Patients With Sleep Apnea
• Study Start Date: Nov 15, 2004
• Actual Primary Completion Date: Dec 15, 2011
• Actual Study Completion Date: Dec 15, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 14 days of Placebo therapy, then CPAP 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 placebo therapy - use of guaifenesin with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation; Other Names: placebo arm, non-CPAP arm
Active Comparator: 14 days of CPAP therapy 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; 14 days of continuous positive airway pressure (CPAP) therapy with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation; Other Names: CPAP arm

Outcome Measures

Primary Outcome Measures

1. Salivary Cortisol Level [Difference between Baseline(Day 0) and Average of Day 1,7,14.]

   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.

2. Epworth Sleepiness Score (ESS) [Difference between Baseline(Day 0) and Average of Day 1,7,14.]

   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.

Secondary Outcome Measures

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

   Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.

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

   Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.

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

   Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.

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

   Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.

5. Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~ 7am, Day 7 [Day 7, 7am]

   Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.

6. Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~11pm, Day 7 [Day 7, 11pm]

   Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.

7. Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~7am, Day 14 [Day 14, 7am]

   Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.

8. Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~11pm, Day 14 [Day 14, 11pm]

   Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

Exclusion Criteria:

• Ages 17 and under

• Pregnant women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Froedtert West Clinics - Otolaryngology Clinc	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Medical College of Wisconsin
• ResMed

Investigators

• Study Chair: 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
• Principal Investigator: B Tucker Woodson, MD, Medical College of Wisconsin

Study Documents (Full-Text)

None provided.

More Information

Publications

• Akerstedt T. Sleepiness as a consequence of shift work. Sleep. 1988 Feb;11(1):17-34. Review.
• Akerstedt T. Work hours and sleepiness. Neurophysiol Clin. 1995;25(6):367-75. Review.
• 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.
• Bradley TD, Phillipson EA. Pathogenesis and pathophysiology of the obstructive sleep apnea syndrome. Med Clin North Am. 1985 Nov;69(6):1169-85. Review.
• Bratel T, Wennlund A, Carlström 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.
• 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.
• 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. Review.
• 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.
• 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.
• 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.
• 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.
• 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.
• Graeber RC: Aircrew fatigue and circadian rhythmicity. In: Wiener E, Nagel DC, eds. Human Factors in Aviation. New York: Academic Press; 1987: 1-48
• 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.
• 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.
• 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.
• Hoddes E, Zarcone V, Smythe H, Phillips R, Dement WC. Quantification of sleepiness: a new approach. Psychophysiology. 1973 Jul;10(4):431-6.
• Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5.
• 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.
• Kecklund G, Akerstedt T. Sleepiness in long distance truck driving: an ambulatory EEG study of night driving. Ergonomics. 1993 Sep;36(9):1007-17.
• Lanfranco F, Gianotti L, Maccario M. Endocrine and metabolic alterations in obstructive sleep apnea syndrome. J Endocrinol Invest. 2003 Jun;26(6):491-2.
• 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.
• 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.
• Lowenstein O, Feinberg R, Loewenfeld ID: Pupillary movements during acute and chronic fatigue. Investigative Ophthalmolog 1963; 2: 138-157
• Lüdtke 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.
• 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
• Merrit SL, Schnyders HC, Mercer P: Circadian aspects of papillary unrest reflecting daytime sleepiness. Sleep Research Online 1999; 2(Sup 1): 773
• 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.
• 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.
• 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).
• 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.
• 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.
• Onusko E. Diagnosing secondary hypertension. Am Fam Physician. 2003 Jan 1;67(1):67-74. Review.
• 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.
• 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.
• Price WJ, Holley DC. Shiftwork and safety in aviation. Occup Med. 1990 Apr-Jun;5(2):343-77. Review.
• Raff H, Findling JW. A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med. 2003 Jun 17;138(12):980-91. Review.
• 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.
• 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
• 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.
• Sullivan CE, Issa FG. Obstructive sleep apnea. Clin Chest Med. 1985 Dec;6(4):633-50.
• 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.
• 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. Review.
• 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.
• 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. Review.
• Wittels EH. Obesity and hormonal factors in sleep and sleep apnea. Med Clin North Am. 1985 Nov;69(6):1265-80. Review.
• 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.

• Responsible Party: Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT01196117
• Other Study ID Numbers: 481-04
• First Posted: Sep 8, 2010
• Last Update Posted: Apr 1, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Medical College of Wisconsin: automatic positive airway pressure (APAP); continuous positive airway pressure (CPAP); Salivary Cortisol; Apnea; Sleep Apnea and/or any Sleep Disordered Breathing
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Respiratory Aspiration; Sleepiness

Study Results

Participant Flow

Recruitment Details	Participants were recruited from sleep clinic patients scheduled for polysomnography.
Pre-assignment Detail	Participants without prior treatment of obstructive sleep apnea (OSA) or overt airway structural pathology that would interfere with continuous positive airway pressure (CPAP) were recruited.

Arm/Group Title	14 Days of Placebo Therapy	14 Days of Continuous Positive Airway Pressure (CPAP) Therapy
Arm/Group Description	14 days of placebo therapy - use of guaifenesin with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation	14 days of continuous positive airway pressure (CPAP) therapy with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation
Period Title: Placebo, Then CPAP
STARTED	18	0
COMPLETED	18	0
NOT COMPLETED	0	0
Period Title: Placebo, Then CPAP
STARTED	0	18
COMPLETED	0	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants received 14 days of placebo therapy then 14 days of continuous positive airway pressure (CPAP) therapy
Overall Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (9)
Sex: Female, Male (Count of Participants)
Female	9 50%
Male	9 50%
Apnea-hyponea Index (AHI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	30.8 (32.1)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	33.8 (6.2)

Outcome Measures

1. Primary Outcome

Title	Salivary Cortisol Level
Description	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.
Time Frame	Difference between Baseline(Day 0) and Average of Day 1,7,14.

Outcome Measure Data

Analysis Population Description

We have made a best faith effort from a manuscript to determine the primary outcome measure; Salivary Cortisol Level; but access to the primary data has been lost and it additionally cannot be found in the manuscript. Despite all efforts to contact the PI/study team members, the statisticians and date are gone.

Arm/Group Title	14 Days of Placebo Therapy	14 Days of CPAP Therapy
Arm/Group Description	14 days of placebo therapy - use of guaifenesin with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation	14 days of continuous positive airway pressure (CPAP) therapy with salivary cortisol measurement
Measure Participants	0	0

2. Primary Outcome

Title	Epworth Sleepiness Score (ESS)
Description	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.
Time Frame	Difference between Baseline(Day 0) and Average of Day 1,7,14.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	14 Days of Placebo Therapy, Then CPAP	14 Days of CPAP Therapy
Arm/Group Description	14 days of placebo therapy - use of guaifenesin with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation	14 days of continuous positive airway pressure (CPAP) therapy with salivary cortisol measurement and Epworth Sleepiness Score (ESS) documentation
Measure Participants	18	18
Median (95% Confidence Interval) [units on a scale]	10.7	8.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~7am, Day 0
Description	Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.
Time Frame	Day 0, 7am

Outcome Measure Data

Analysis Population Description

A sub-analysis was performed on those using CPAP>= 3 hours per night compared to those who used CPAP< 3 hours per night

Arm/Group Title	CPAP>= 3 Hours Per Night	CPAP<3 Hours Per Night
Arm/Group Description	The average nightly CPAP use in the group using CPAP for >=3 hours (N=9) was 311 minutes (180-444) minutes.	In the group using CPAP for <3hours (N=9), it was 33 minutes (2-85) minutes.
Measure Participants	9	9
Median (95% Confidence Interval) [nmol/l]	12.5	12.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8938
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~11pm, Day 0
Description	Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.
Time Frame	Day 0, 11pm

Outcome Measure Data

Analysis Population Description

A sub-analysis was performed on those using CPAP>= 3 hours per night compared to those who used CPAP< 3 hours per night

Arm/Group Title	CPAP>= 3 Hours Per Night	CPAP<3 Hours Per Night
Arm/Group Description	The average nightly CPAP use in the group using CPAP for >=3 hours (N=9) was 311 minutes (180-444) minutes.	In the group using CPAP for <3hours (N=9), it was 33 minutes (2-85) minutes.
Measure Participants	9	9
Median (95% Confidence Interval) [nmol/l]	3.2	1.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.014
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~7am, Day 1
Description	Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.
Time Frame	Day 1, 7am

Outcome Measure Data

Analysis Population Description

A sub-analysis was performed on those using CPAP>= 3 hours per night compared to those who used CPAP< 3 hours per night

Arm/Group Title	CPAP>= 3 Hours Per Night	CPAP<3 Hours Per Night
Arm/Group Description	The average nightly CPAP use in the group using CPAP for >=3 hours (N=9) was 311 minutes (180-444) minutes.	In the group using CPAP for <3hours (N=9), it was 33 minutes (2-85) minutes.
Measure Participants	9	9
Median (95% Confidence Interval) [nmol/l]	7.4	13.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0200
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~11pm, Day 1
Description	Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.
Time Frame	Day 1, 11pm

Outcome Measure Data

Analysis Population Description

A sub-analysis was performed on those using CPAP>= 3 hours per night compared to those who used CPAP< 3 hours per night

Arm/Group Title	CPAP>= 3 Hours Per Night	CPAP<3 Hours Per Night
Arm/Group Description	The average nightly CPAP use in the group using CPAP for >=3 hours (N=9) was 311 minutes (180-444) minutes.	In the group using CPAP for <3hours (N=9), it was 33 minutes (2-85) minutes.
Measure Participants	9	9
Median (95% Confidence Interval) [nmol/l]	2.2	1.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1321
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~ 7am, Day 7
Description	Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.
Time Frame	Day 7, 7am

Outcome Measure Data

Analysis Population Description

A sub-analysis was performed on those using CPAP>= 3 hours per night compared to those who used CPAP< 3 hours per night

Arm/Group Title	CPAP>= 3 Hours Per Night	CPAP<3 Hours Per Night
Arm/Group Description	The average nightly CPAP use in the group using CPAP for >=3 hours (N=9) was 311 minutes (180-444) minutes.	In the group using CPAP for <3hours (N=9), it was 33 minutes (2-85) minutes.
Measure Participants	9	9
Mean (95% Confidence Interval) [nmol/l]	9.9	13.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.2490
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~11pm, Day 7
Description	Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.
Time Frame	Day 7, 11pm

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP>= 3 Hours Per Night	CPAP<3 Hours Per Night
Arm/Group Description	The average nightly CPAP use in the group using CPAP for >=3 hours (N=9) was 311 minutes (180-444) minutes.	In the group using CPAP for <3hours (N=9), it was 33 minutes (2-85) minutes.
Measure Participants	9	9
Median (95% Confidence Interval) [nmol/l]	3.0	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5139
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~7am, Day 14
Description	Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.
Time Frame	Day 14, 7am

Outcome Measure Data

Analysis Population Description

A sub-analysis was performed on those using CPAP>= 3 hours per night compared to those who used CPAP< 3 hours per night

Arm/Group Title	CPAP>= 3 Hours Per Night	CPAP<3 Hours Per Night
Arm/Group Description	The average nightly CPAP use in the group using CPAP for >=3 hours (N=9) was 311 minutes (180-444) minutes.	In the group using CPAP for <3hours (N=9), it was 33 minutes (2-85) minutes.
Measure Participants	9	9
Median (95% Confidence Interval) [nmol/l]	9.2	15.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0597
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Salivary Cortisol in Participants Who Used Continuous Positive Airway Pressure (CPAP) at ~11pm, Day 14
Description	Salivary Cortisol was measured by enzyme-linked immunosorbent assay. The reference range for healthy adults is <4.2 nmol/l.
Time Frame	Day 14, 11pm

Outcome Measure Data

Analysis Population Description

A sub-analysis was performed on those using CPAP>= 3 hours per night compared to those who used CPAP< 3 hours per night

Arm/Group Title	CPAP>= 3 Hours Per Night	CPAP<3 Hours Per Night
Arm/Group Description	The average nightly CPAP use in the group using CPAP for >=3 hours (N=9) was 311 minutes (180-444) minutes.	In the group using CPAP for <3hours (N=9), it was 33 minutes (2-85) minutes.
Measure Participants	9	9
Median (95% Confidence Interval) [nmol/l]	1.9	2.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	14 Days of Placebo Therapy, 14 Days of CPAP Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2134
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Adverse Events were observed in a non-systematic way over the course of approximately 6 years the patients were enrolled.
Adverse Event Reporting Description	Given the minimal risk nature of this study, adverse events were collected via a non-systematic assessment. The primary risks were loss of confidentiality, some possible discomfort from the mask and the possibility of an adverse event related to the mucolytic, guaifenesin. None of these possible adverse events occurred and they were not collected in a systematic way.
Arm/Group Title	14 Days of Placebo Therapy, Then CPAP		14 Days of CPAP Therapy
Arm/Group Description	14 days of placebo therapy: 14 days of placebo therapy then 14 days of continuous positive airway pressure (CPAP) therapy		14 days of continuous positive airway pressure (CPAP) therapy
All Cause Mortality
	14 Days of Placebo Therapy, Then CPAP		14 Days of CPAP Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Serious Adverse Events
	14 Days of Placebo Therapy, Then CPAP		14 Days of CPAP Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	14 Days of Placebo Therapy, Then CPAP		14 Days of CPAP Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)

Limitations/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.

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.