Apnea Positive Pressure Long-Term Efficacy Study

NCT ID: NCT00051363

Last Updated: 2018-11-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-09-30
• Study Completion Date: 2008-09-30

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).

Detailed Description

BACKGROUND:

Nasal CPAP therapy is in widespread use as the primary treatment for OSAS, a sleep-related breathing disorder affecting more than 15 million Americans. The therapeutic effectiveness of CPAP in providing significant, stable, and long-term neurocognitive or other functional benefits to patients with OSAS has not been systematically investigated.

DESIGN NARRATIVE:

The study is a randomized, blinded, sham-controlled, multi-center trial of CPAP therapy. The principal aims of the study are: 1) to assess the long-term effectiveness of CPAP therapy on neurocognitive function, mood, sleepiness, and quality of life by administering tests of these indices to subjects randomly assigned to active or sham CPAP; 2) to identify specific neurocognitive deficits associated with OSAS in a large, heterogeneous subject population; 3) to determine which deficits in neurocognitive function in OSAS subjects are reversible and most sensitive to the effects of CPAP; 4) to develop a composite multivariate outcome measure from the results of this study that can be used to assess the clinical effectiveness of CPAP in improving neurocognitive function, mood, sleepiness, and quality of life; and 5) to use functional magnetic resonance imaging to compare cortical activation before and after CPAP therapy, and to assess whether this change is associated with improvement in specific neurocognitive task performance. The primary endpoint of the study is the effect of six months of CPAP treatment on neurocognitive function. A total of 1100 subjects (550 per treatment group) will be enrolled from the patient populations at five sites (Stanford University; University of Arizona; Brigham and Women's Hospital; Massachusetts; St. Luke's Hospital, Missouri; St. Mary Medical Center, Washington).

Conditions

Lung Diseases; Sleep Apnea Syndromes; Sleep

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active CPAP

Active Continuous Positive Airway Pressure (CPAP)

Group Type: ACTIVE_COMPARATOR

Active CPAP

Intervention Type: DEVICE

Nightly nasal continuous positive airway pressure (CPAP)

Sham CPAP

Sham Continuous Positive Airway Pressure (CPAP)

Group Type: PLACEBO_COMPARATOR

Sham CPAP

Intervention Type: DEVICE

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

Interventions

Active CPAP

Nightly nasal continuous positive airway pressure (CPAP)

Intervention Type: DEVICE

Sham CPAP

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

Intervention Type: DEVICE

Other Intervention Names

Positive Pressure Respiration; Sham CPAP machine

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)
• Cancer, unless in remission for greater than one year and not taking exclusionary medications
• 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
• Any illicit drug usage or marijuana usage more than once a week
• Any individual in the household currently on CPAP or on CPAP in the past
• A score of 26 or less on the Mini Mental State Examination (MMSE)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Clete A. Kushida

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William C. Dement, MD, PhD

Role: STUDY_CHAIR

Stanford University

Clete A. Kushida, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

University of Arizona AHSC

Tucson, Arizona, United States

Stanford University School of Medicine

Palo Alto, California, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

St. Luke's Hospital

Chesterfield, Missouri, United States

St. Mary Medical Center

Walla Walla, Washington, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17561541 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22138103 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20619727 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21358847 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23204602 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18853696 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24127141 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24910546 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25232509 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24634638 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24916094 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24808886 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23227139 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21358846 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26518698 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27242272 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39572221 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36917194 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32190413 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28899524 (View on PubMed)

Other Identifiers

U01HL068060

Identifier Type: NIH

Identifier Source: secondary_id

View Link

150

Identifier Type: -

Identifier Source: org_study_id