Apnea Positive Pressure Long-Term Efficacy Study

NCT00051363 | Completed Phase 3 Results DMC

• 2 other identifiers: 150U01HL068060
• Study Type: interventional
• Target: 1,105
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine the effectiveness of nasal continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnea syndrome (OSAS).

Conditions

Lung Diseases; Sleep Apnea Syndromes; Sleep

Keywords

Obstructive Sleep Apnea

Outcome Measures

Primary Outcomes (3)

• Effect of CPAP on Neurocognitive Function: E/F Function- SWMT-OMD

  There are three primary measures of neurocognitive function measured for APPLES, each representing a different domain: Executive and Frontal-lobe (E/F) Function- Sustained Working Memory Test Overall Mid-Day Index (SWMT-OMD), Attention and Psychomotor (A/P) Function- Pathfinder Number Test Total Time (PFN-TOTL), and Learning and Memory (L/M) Function- Buschke Selective Reminding Test Sum Recall (BSRT-SR). This is domain #1: Executive and Frontal-lobe (E/F) Function- Sustained Working Memory Test Overall Mid-Day Index (SWMT-OMD) SWMT-OMD is a scaled score that indicates whether the participant scored lower or higher relative to baseline using standard deviation units. It is computed as the mean of three sub-scores, one based on working memory (WM) task performance (behavioral WM sub-score: speed, accuracy), and the other two on electroencephalogram (EEG) (cortical activation sub-score: neural workload, attentional effort during WM task; alertness sub-score: resting alertness).

  2 months and 6 months post intervention

• Effect of CPAP on Neurocognitive Function: A/P Function- PFN-TOTL

  There are three primary measures of neurocognitive function measured for APPLES, each representing a different domain: Executive and Frontal-lobe (E/F) Function- Sustained Working Memory Test Overall Mid-Day Index (SWMT-OMD), Attention and Psychomotor (A/P) Function- Pathfinder Number Test Total Time (PFN-TOTL), and Learning and Memory (L/M) Function- Buschke Selective Reminding Test Sum Recall (BSRT-SR). This is domain #2: Attention and Psychomotor (A/P) Function- Pathfinder Number Test Total Time (PFN-TOTL)

  Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention

• Effect of CPAP on Neurocognitive Function: L/M Function- BSRT-SR

  There are three primary measures of neurocognitive function measured for APPLES, each representing a different domain: Executive and Frontal-lobe (E/F) Function- Sustained Working Memory Test Overall Mid-Day Index (SWMT-OMD), Attention and Psychomotor (A/P) Function- Pathfinder Number Test Total Time (PFN-TOTL), and Learning and Memory (L/M) Function- Buschke Selective Reminding Test Sum Recall (BSRT-SR). This is domain #3: Learning and Memory (L/M) Function- Buschke Selective Reminding Test Sum Recall (BSRT-SR)

  Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention

Secondary Outcomes (11)

• Attention and Psychomotor (A/P) Function: Pathfinder Number- Reaction Time (PN-RT)

  2 months and 6 months post intervention

• Attention and Psychomotor (A/P) Function: Psychomotor Vigilance Task- Median Reaction Time (PVT-MedRT)

  2 months and 6 months post intervention

• Attention and Psychomotor (A/P) Function: PVT- Mean Slowest 10% of Reaction Times (PVT-Slo10%RT)

  2 months and 6 months post intervention

• Learning and Memory (L/M) Function: Buschke Selective Reminding Test Delayed Recall- Total Recall (BSRTDR-TotRec)

  2 months and 6 months post intervention

• Executive and Frontal-Lobe (E/F) Function: Sustained Working Memory Test- Mid-day Behavioral Index (SWMT-BehMD)

  2 months and 6 months post intervention

Other Outcomes (1)

• Functional Magnetic Resonance Imaging (fMRI)

  Measured at diagnostic visit (baseline) and 6 months post intervention

Study Arms (2)

Active CPAP

ACTIVE COMPARATOR

Active Continuous Positive Airway Pressure (CPAP)

Device: Active CPAP

Sham CPAP

PLACEBO COMPARATOR

Sham Continuous Positive Airway Pressure (CPAP)

Device: Sham CPAP

Interventions

Active CPAP DEVICE

Nightly nasal continuous positive airway pressure (CPAP)

Also known as: Positive Pressure Respiration

Active CPAP

Sham CPAP DEVICE

Sham CPAP machine will be used for participants in the placebo group.

Also known as: Sham CPAP machine

Sham CPAP

Eligibility Criteria

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

You may qualify if:

• Male or female adults age 18 years or older with a diagnosis of OSAS using clinical criteria defined by the study protocol
• Study participation may require seven or more laboratory visits over six months

You may not qualify if:

• Prior treatment for OSAS with continuous positive airway pressure or surgery
• Potential sleep apnea complications that may affect the health or safety of the participant, including low blood oxygen, recent near-miss or prior automobile accident due to sleepiness, congestive heart failure, history of angina, coronary artery disease, myocardial infarction or stroke, cardiac rhythm disturbance, and chronic neurological disorders affecting neurocognitive abilities or daily function
• The use of hypnotics, anxiolytics, sedating antidepressants, anticonvulsants, sedating antihistamines, stimulants or other medications likely to affect neurocognitive function and/or alertness
• Respiratory disease requiring medications (unless on stable medications for 2 months)
• Self-reported renal failure
• Pregnancy anytime during a subject's participation
• Psychiatric illness, as defined by a DSM-IV diagnosis, except for depression or mild anxiety
• Narcolepsy, idiopathic hypersomnolence, DSM-IV chronic insomnia, restless legs syndrome, or rapid eye movement (REM) behavior disorder
• Current use of diurnal or nocturnal supplemental oxygen
• Significant vision, hearing, or coordination problems
• Difficulty understanding or speaking English
• Currently working night or rotating shifts
• Consumption of more than 10 caffeinated beverages per day (approximately 1,000 mg per day)
• Smokers whose habit interferes with the overnight polysomnogram or with the battery of testing during the day
• Consumption of more than 2 alcoholic beverages per day

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (5)

University of Arizona AHSC

Tucson, Arizona, 85724, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94305, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02459, United States

Location

St. Luke's Hospital

Chesterfield, Missouri, 63017, United States

Location

St. Mary Medical Center

Walla Walla, Washington, 99362, United States

Location

Related Publications (20)

• Kushida CA, Nichols DA, Quan SF, Goodwin JL, White DP, Gottlieb DJ, Walsh JK, Schweitzer PK, Guilleminault C, Simon RD, Leary EB, Hyde PR, Holmes TH, Bloch DA, Green S, McEvoy LK, Gevins A, Dement WC. The Apnea Positive Pressure Long-term Efficacy Study (APPLES): rationale, design, methods, and procedures. J Clin Sleep Med. 2006 Jul 15;2(3):288-300.

  PMID: 17561541 BACKGROUND

• Holmes TH, Nichols DA, Thomander D, Kushida CA. A method for estimating normative distributions for study-specific populations of clinical trials. Contemp Clin Trials. 2012 Mar;33(2):445-9. doi: 10.1016/j.cct.2011.11.014. Epub 2011 Nov 25.

  PMID: 22138103 BACKGROUND

• Gevins A, Smith ME, McEvoy LK, Ilan AB, Chan CS, Jiang A, Sam-Vargas L, Abraham G. A cognitive and neurophysiological test of change from an individual's baseline. Clin Neurophysiol. 2011 Jan;122(1):114-20. doi: 10.1016/j.clinph.2010.06.010. Epub 2010 Jul 8.

  PMID: 20619727 BACKGROUND

• Quan SF, Chan CS, Dement WC, Gevins A, Goodwin JL, Gottlieb DJ, Green S, Guilleminault C, Hirshkowitz M, Hyde PR, Kay GG, Leary EB, Nichols DA, Schweitzer PK, Simon RD, Walsh JK, Kushida CA. The association between obstructive sleep apnea and neurocognitive performance--the Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep. 2011 Mar 1;34(3):303-314B. doi: 10.1093/sleep/34.3.303.

  PMID: 21358847 RESULT

• Kushida CA, Nichols DA, Holmes TH, Quan SF, Walsh JK, Gottlieb DJ, Simon RD Jr, Guilleminault C, White DP, Goodwin JL, Schweitzer PK, Leary EB, Hyde PR, Hirshkowitz M, Green S, McEvoy LK, Chan C, Gevins A, Kay GG, Bloch DA, Crabtree T, Dement WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep. 2012 Dec 1;35(12):1593-602. doi: 10.5665/sleep.2226.

  PMID: 23204602 RESULT

• Vasquez MM, Goodwin JL, Drescher AA, Smith TW, Quan SF. Associations of dietary intake and physical activity with sleep disordered breathing in the Apnea Positive Pressure Long-Term Efficacy Study (APPLES). J Clin Sleep Med. 2008 Oct 15;4(5):411-8.

  PMID: 18853696 RESULT

• Quan SF, Budhiraja R, Clarke DP, Goodwin JL, Gottlieb DJ, Nichols DA, Simon RD, Smith TW, Walsh JK, Kushida CA. Impact of treatment with continuous positive airway pressure (CPAP) on weight in obstructive sleep apnea. J Clin Sleep Med. 2013 Oct 15;9(10):989-93. doi: 10.5664/jcsm.3064.

  PMID: 24127141 RESULT

• Batool-Anwar S, Goodwin JL, Drescher AA, Baldwin CM, Simon RD, Smith TW, Quan SF. Impact of CPAP on activity patterns and diet in patients with obstructive sleep apnea (OSA). J Clin Sleep Med. 2014 May 15;10(5):465-72. doi: 10.5664/jcsm.3686.

  PMID: 24910546 RESULT

• Quan SF, Budhiraja R, Batool-Anwar S, Gottlieb DJ, Eichling P, Patel S, Shen W, Walsh JK, Kushida CA. Lack of Impact of Mild Obstructive Sleep Apnea on Sleepiness, Mood and Quality of Life. Southwest J Pulm Crit Care. 2014;9(1):44-56. doi: 10.13175/swjpcc082-14.

  PMID: 25232509 RESULT

• Quan SF, Budhiraja R, Clarke DP, Goodwin JL, Gottlieb DJ, Nichols DA, Simon RD, Smith TW, Walsh JK, Kushida CA, Phillips B. You still need more than CPAP for OSA patients to lose weight. J Clin Sleep Med. 2014 Mar 15;10(3):349. doi: 10.5664/jcsm.3552. No abstract available.

  PMID: 24634638 RESULT

• Prilipko O, Huynh N, Thomason ME, Kushida CA, Guilleminault C. An fMRI study of cerebrovascular reactivity and perfusion in obstructive sleep apnea patients before and after CPAP treatment. Sleep Med. 2014 Aug;15(8):892-8. doi: 10.1016/j.sleep.2014.04.004. Epub 2014 May 4.

  PMID: 24916094 RESULT

• Huynh NT, Prilipko O, Kushida CA, Guilleminault C. Volumetric Brain Morphometry Changes in Patients with Obstructive Sleep Apnea Syndrome: Effects of CPAP Treatment and Literature Review. Front Neurol. 2014 Apr 29;5:58. doi: 10.3389/fneur.2014.00058. eCollection 2014.

  PMID: 24808886 RESULT

• Prilipko O, Huynh N, Schwartz S, Tantrakul V, Kushida C, Paiva T, Guilleminault C. The effects of CPAP treatment on task positive and default mode networks in obstructive sleep apnea patients: an fMRI study. PLoS One. 2012;7(12):e47433. doi: 10.1371/journal.pone.0047433. Epub 2012 Dec 5.

  PMID: 23227139 RESULT

• Prilipko O, Huynh N, Schwartz S, Tantrakul V, Kim JH, Peralta AR, Kushida C, Paiva T, Guilleminault C. Task positive and default mode networks during a parametric working memory task in obstructive sleep apnea patients and healthy controls. Sleep. 2011 Mar 1;34(3):293-301A. doi: 10.1093/sleep/34.3.293.

  PMID: 21358846 RESULT

• Budhiraja R, Kushida CA, Nichols DA, Walsh JK, Simon RD, Gottlieb DJ, Quan SF. Impact of Randomization, Clinic Visits, and Medical and Psychiatric Cormorbidities on Continuous Positive Airway Pressure Adherence in Obstructive Sleep Apnea. J Clin Sleep Med. 2016 Mar;12(3):333-41. doi: 10.5664/jcsm.5578.

  PMID: 26518698 RESULT

• Batool-Anwar S, Goodwin JL, Kushida CA, Walsh JA, Simon RD, Nichols DA, Quan SF. Impact of continuous positive airway pressure (CPAP) on quality of life in patients with obstructive sleep apnea (OSA). J Sleep Res. 2016 Dec;25(6):731-738. doi: 10.1111/jsr.12430. Epub 2016 May 30.

  PMID: 27242272 RESULT

• Zinchuk AV, Kushida CA, Walker A, Wellman A, Azarbarzin A, Alex RM, Varga AW, Sands SA, Yaggi HK. Arousal threshold modifies the effect of CPAP on executive function among individuals with obstructive sleep apnoea. Eur Respir J. 2025 Feb 13;65(2):2401183. doi: 10.1183/13993003.01183-2024. Print 2025 Feb.

  PMID: 39572221 DERIVED

• Knauert MP, Adekolu O, Xu Z, Deng A, Chu JH, Baldassarri SR, Kushida C, Yaggi HK, Zinchuk A. Morning Chronotype Is Associated with Improved Adherence to Continuous Positive Airway Pressure among Individuals with Obstructive Sleep Apnea. Ann Am Thorac Soc. 2023 Aug;20(8):1182-1191. doi: 10.1513/AnnalsATS.202210-885OC.

  PMID: 36917194 DERIVED

• Batool-Anwar S, Omobomi O, Quan SF. The effect of CPAP on HRQOL as measured by the Quality of Well-Being Self Administered Questionaire (QWB-SA). Southwest J Pulm Crit Care. 2020;20(1):29-40. doi: 10.13175/swjpcc070-19.

  PMID: 32190413 DERIVED

• Holmes TH, Kushida CA. Adherence to continuous positive airway pressure improves attention/psychomotor function and sleepiness: a bias-reduction method with further assessment of APPLES. Sleep Med. 2017 Sep;37:130-134. doi: 10.1016/j.sleep.2017.06.022. Epub 2017 Jul 14.

  PMID: 28899524 DERIVED

MeSH Terms

Conditions

Lung Diseases; Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Interventions

Positive-Pressure Respiration

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Limitations and Caveats

There are study sample limitations because although participants with severe OSA were included, those who had the lowest oxygen saturation, a history of sleepiness-related accidents, or major cardiovascular comorbidities were excluded.

Results Point of Contact

• Title: Deborah A. Nichols
• Organization: Stanford University

dnichols@cableone.net

208-908-7364

Study Officials

• William C. Dement, MD, PhD

  Stanford University

  STUDY CHAIR

• Clete A. Kushida, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2003
• First Posted: January 13, 2003
• Study Start: September 1, 2002
• Primary Completion: August 1, 2008
• Study Completion: September 1, 2008
• Last Updated: November 28, 2018
• Results First Posted: November 30, 2016

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will share

Locations

US (5)