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).
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,105
Nightly nasal continuous positive airway pressure (CPAP)
Sham CPAP machine will be used for participants in the placebo group.
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
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).
Time frame: 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)
Time frame: 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)
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St. Mary Medical Center
Walla Walla, Washington, United States
Time frame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
Attention and Psychomotor (A/P) Function: Pathfinder Number- Reaction Time (PN-RT)
The APPLES a priori Secondary Neurocognitive Analysis Plan specified a dimension reduction method to reduce twelve secondary neurocognitive variables from three neurocognitive domains to seven variables from three neurocognitive domains. Three of the selected variables came from the domain of Attention and Psychomotor (A/P) Function: Pathfinder Number- Reaction Time (PN-RT), Psychomotor Vigilance Task- Median Reaction Time (PVT-MedRT), and PVT- Mean Slowest 10% of Reaction Times (PVT-Slo10%RT). These data are for variable #1: Pathfinder Number- Reaction Time (PN-RT)
Time frame: 2 months and 6 months post intervention
Attention and Psychomotor (A/P) Function: Psychomotor Vigilance Task- Median Reaction Time (PVT-MedRT)
The APPLES a priori Secondary Neurocognitive Analysis Plan specified a dimension reduction method to reduce twelve secondary neurocognitive variables from three neurocognitive domains to seven variables from three neurocognitive domains. Three of the selected variables came from the domain of Attention and Psychomotor (A/P) Function: Pathfinder Number- Reaction Time (PN-RT), Psychomotor Vigilance Task- Median Reaction Time (PVT-MedRT), and PVT- Mean Slowest 10% of Reaction Times (PVT-Slo10%RT). These data are for variable #2: Psychomotor Vigilance Task- Median Reaction Time (PVT-MedRT)
Time frame: 2 months and 6 months post intervention
Attention and Psychomotor (A/P) Function: PVT- Mean Slowest 10% of Reaction Times (PVT-Slo10%RT)
The APPLES a priori Secondary Neurocognitive Analysis Plan specified a dimension reduction method to reduce twelve secondary neurocognitive variables from three neurocognitive domains to seven variables from three neurocognitive domains. Three of the selected variables came from the domain of Attention and Psychomotor (A/P) Function: Pathfinder Number- Reaction Time (PN-RT), Psychomotor Vigilance Task- Median Reaction Time (PVT-MedRT), and PVT- Mean Slowest 10% of Reaction Times (PVT-Slo10%RT). These data are for variable #3: PVT- Mean Slowest 10% of Reaction Times (PVT-Slo10%RT)
Time frame: 2 months and 6 months post intervention
Learning and Memory (L/M) Function: Buschke Selective Reminding Test Delayed Recall- Total Recall (BSRTDR-TotRec)
The APPLES a priori Secondary Neurocognitive Analysis Plan specified a dimension reduction method to reduce twelve secondary neurocognitive variables from three neurocognitive domains to seven variables from three neurocognitive domains. One of the selected variables came from the domain of Learning and Memory (L/M) Function: Buschke Selective Reminding Test Delayed Recall- Total Recall (BSRTDR-TotRec).
Time frame: 2 months and 6 months post intervention
Executive and Frontal-Lobe (E/F) Function: Sustained Working Memory Test- Mid-day Behavioral Index (SWMT-BehMD)
The APPLES a priori Secondary Neurocognitive Analysis Plan specified a dimension reduction method to reduce twelve secondary neurocognitive variables from three neurocognitive domains to seven variables from three neurocognitive domains. Three of the selected variables came from the domain of Executive and Frontal-Lobe (E/F) Function: SWMT-BehMD, SWMT-ActMD, and SAT-D-NumRuCh. These data are for variable #1: Sustained Working Memory Test- Mid-day Behavioral Index (SWMT-BehMD) SWMT-BehMD 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 difference from baseline relative to measures of working memory (WM) task performance accuracy (percent correct) and mean and standard deviation of reaction time (milliseconds). High-load WM tasks receive twice the weight of the low-load WM tasks.
Time frame: 2 months and 6 months post intervention
Executive and Frontal-Lobe (E/F) Function: SWMT- Mid-day Activation Index (SWMT-ActMD)
The APPLES a priori Secondary Neurocognitive Analysis Plan specified a dimension reduction method to reduce twelve secondary neurocognitive variables from three neurocognitive domains to seven variables from three neurocognitive domains. Three of the selected variables came from the domain of Executive and Frontal-Lobe (E/F) Function: SWMT-BehMD, SWMT-ActMD, and SAT-D-NumRuCh. These data are for variable #2: SWMT- Mid-day Activation Index (SWMT-ActMD) SWMT-ActMD is a scaled score that indicates whether the participant scored lower or higher relative to baseline (BL) using standard deviation units. It is computed as the difference from BL relative to EEG power spectral variables (decibels) measured during the easier vs. more difficult working memory (WM) tasks. A positive activation sub-score indicates a larger cortical neuronal population was recruited to perform the more difficult WM task relative to BL, while a negative score indicates a smaller population was recruited.
Time frame: 2 months and 6 months post intervention
Executive and Frontal-Lobe (E/F) Function: Shifting Attention Test Discovery Condition- Number of Rule Changes (SAT-D-NumRuCh)
The APPLES a priori Secondary Neurocognitive Analysis Plan specified a dimension reduction method to reduce twelve secondary neurocognitive variables from three neurocognitive domains to seven variables from three neurocognitive domains. Three of the selected variables came from the domain of Executive and Frontal-Lobe (E/F) Function: Sustained Working Memory Test- Mid-day Behavioral Index (SWMT-BehMD), SWMT- Mid-day Activation Index (SWMT-ActMD), and Shifting Attention Test Discovery Condition- Number of Rule Changes (SAT-D-NumRuCh). These data are for variable #3: Shifting Attention Test Discovery Condition- Number of Rule Changes (SAT-D-NumRuCh)
Time frame: 2 months and 6 months post intervention
Objective Sleepiness/Alertness: Maintenance of Wakefulness Test- Mean Sleep Latency (MWT-MSL)
Objective sleepiness/alertness was measured using the Maintenance of Wakefulness Test (MWT); the outcome variable was MWT Mean Sleep Latency (MWT-MSL). The MWT was administered using four twenty-minute trials where the participant was asked to sit in a chair, in a quiet and dimly lit room, with instructions to stay awake. Trials were performed at 10 AM, Noon, 2 PM and 4 PM. The mean sleep latency was calculated using the 4 trials from a given visit, and required that at least 3 of the 4 trials were performed and validated.
Time frame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
Subjective Sleepiness/Alertness: Epworth Sleepiness Scale- Total Score (ESS-TS)
Subjective sleepiness/alertness was measured using the Epworth Sleepiness Scale (ESS); the outcome variable was ESS Total Score (ESS-TS). The ESS is a validated questionnaire (8 questions) that ask the chances of dozing off in specific situations. Summing the scores produces a scaled total score between 0 and 24, with higher numbers indicating more subjective sleepiness. The ESS was administered the evening before the polysomnogram (PSG), or overnight sleep study. Data reported here include questionnaires collected at the DX, 2M, and 6M visits.
Time frame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
Mood
Time frame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
Quality of Life: Calgary Sleep Apnea Quality of Life Index- Total Score (SAQLI-TS)
Quality of life was measured using the Calgary Sleep Apnea Quality of Life Index (SAQLI), which is an interview-administered instrument with high internal consistency and reliability. The SAQLI was designed to assess components identified as important to patients including daily functioning, social interactions, emotional functioning, symptoms experienced, and treatment-related symptoms. Items are scored on a seven-point scale, averaged (taking into account treatment-related symptoms), to yield a composite score between 1 and 7, where higher scores represent better quality of life.
Time frame: diagnostic visit (baseline)