APPLES: Apnea Positive Pressure Long-Term Efficacy Study
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Lung Diseases
- Sponsor
- Stanford University
- Enrollment
- 1105
- Locations
- 5
- Primary Endpoint
- Effect of CPAP on Neurocognitive Function: L/M Function- BSRT-SR
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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).
Investigators
Clete A. Kushida
Principal Investigator
Stanford University
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
Outcomes
Primary Outcomes
Effect of CPAP on Neurocognitive Function: L/M Function- BSRT-SR
Time Frame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
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)
Effect of CPAP on Neurocognitive Function: E/F Function- SWMT-OMD
Time Frame: 2 months and 6 months post intervention
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).
Effect of CPAP on Neurocognitive Function: A/P Function- PFN-TOTL
Time Frame: Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention
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)
Secondary Outcomes
- Attention and Psychomotor (A/P) Function: Psychomotor Vigilance Task- Median Reaction Time (PVT-MedRT)(2 months and 6 months post intervention)
- Subjective Sleepiness/Alertness: Epworth Sleepiness Scale- Total Score (ESS-TS)(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)(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: SWMT- Mid-day Activation Index (SWMT-ActMD)(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)(2 months and 6 months post intervention)
- Quality of Life: Calgary Sleep Apnea Quality of Life Index- Total Score (SAQLI-TS)(diagnostic visit (baseline))
- Attention and Psychomotor (A/P) Function: PVT- Mean Slowest 10% of Reaction Times (PVT-Slo10%RT)(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)
- Objective Sleepiness/Alertness: Maintenance of Wakefulness Test- Mean Sleep Latency (MWT-MSL)(Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention)
- Mood(Measured at diagnostic visit (baseline) and 2 months and 6 months post intervention)