Clinical trial NCT00051363: Apnea Positive Pressure Long-Term Efficacy Study
Official title: APPLES: Apnea Positive Pressure Long-Term Efficacy Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Diseases
Sleep Apnea Syndromes
Sleep
Keywords: Obstructive Sleep Apnea
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2003-01-13
Enrollment: 1105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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)

Primary outcomes:
measure: Effect of CPAP on Neurocognitive Function: E/F Function- SWMT-OMD
timeFrame: 2 months and 6 months post intervention
measure: Effect of CPAP on Neurocognitive Function: A/P Function- PFN-TOTL
timeFrame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
measure: Effect of CPAP on Neurocognitive Function: L/M Function- BSRT-SR
timeFrame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
Secondary outcomes:
measure: Attention and Psychomotor (A/P) Function: Pathfinder Number- Reaction Time (PN-RT)
timeFrame: 2 months and 6 months post intervention
measure: Attention and Psychomotor (A/P) Function: Psychomotor Vigilance Task- Median Reaction Time (PVT-MedRT)
timeFrame: 2 months and 6 months post intervention
measure: Attention and Psychomotor (A/P) Function: PVT- Mean Slowest 10% of Reaction Times (PVT-Slo10%RT)
timeFrame: 2 months and 6 months post intervention
measure: Learning and Memory (L/M) Function: Buschke Selective Reminding Test Delayed Recall- Total Recall (BSRTDR-TotRec)
timeFrame: 2 months and 6 months post intervention
measure: Executive and Frontal-Lobe (E/F) Function: Sustained Working Memory Test- Mid-day Behavioral Index (SWMT-BehMD)
timeFrame: 2 months and 6 months post intervention
measure: Executive and Frontal-Lobe (E/F) Function: SWMT- Mid-day Activation Index (SWMT-ActMD)
timeFrame: 2 months and 6 months post intervention
measure: Executive and Frontal-Lobe (E/F) Function: Shifting Attention Test Discovery Condition- Number of Rule Changes (SAT-D-NumRuCh)
timeFrame: 2 months and 6 months post intervention
measure: Objective Sleepiness/Alertness: Maintenance of Wakefulness Test- Mean Sleep Latency (MWT-MSL)
timeFrame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
measure: Subjective Sleepiness/Alertness: Epworth Sleepiness Scale- Total Score (ESS-TS)
timeFrame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
measure: Mood
timeFrame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
measure: Quality of Life: Calgary Sleep Apnea Quality of Life Index- Total Score (SAQLI-TS)
timeFrame: diagnostic visit (baseline)
Other outcomes:
measure: Functional Magnetic Resonance Imaging (fMRI)
timeFrame: Measured at diagnostic visit (baseline) and 6 months post intervention
Locations:
city: Tucson
country: United States
facility: University of Arizona AHSC
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Chesterfield
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Walla Walla
country: United States
facility: St. Mary Medical Center
state: Washington
Study officials:
affiliation: Stanford University
name: William C. Dement, MD, PhD
role: STUDY_CHAIR
affiliation: Stanford University
name: Clete A. Kushida, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.