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Completed

NCT Number: NCT00051363

Apnea Positive Pressure Long-Term Efficacy Study

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).

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Key information

Conditions

Lung Diseases Apnea Dyssomnias Nervous System Diseases Respiration Disorders Respiratory Tract Diseases Sleep Sleep Apnea Syndromes Sleep Apnea, Obstructive Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Arizona AHSC, Tucson, Arizona, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Active CPAP

Device

Nightly nasal continuous positive airway pressure (CPAP)

Other names: Positive Pressure Respiration

Sham CPAP

Device

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

Other names: Sham CPAP machine

Primary outcomes

  1. 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).

  2. 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)

  3. 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)

Secondary outcomes

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

    Time frame: 2 months and 6 months post intervention

    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)

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

    Time frame: 2 months and 6 months post intervention

    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)

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

    Time frame: 2 months and 6 months post intervention

    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)

  4. 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

    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).

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

    Time frame: 2 months and 6 months post intervention

    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.

  6. Executive and Frontal-Lobe (E/F) Function: SWMT- Mid-day Activation Index (SWMT-ActMD)

    Time frame: 2 months and 6 months post intervention

    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.

  7. Executive and Frontal-Lobe (E/F) Function: Shifting Attention Test Discovery Condition- Number of Rule Changes (SAT-D-NumRuCh)

    Time frame: 2 months and 6 months post intervention

    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)

  8. Objective Sleepiness/Alertness: Maintenance of Wakefulness Test- Mean Sleep Latency (MWT-MSL)

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

    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.

  9. Subjective Sleepiness/Alertness: Epworth Sleepiness Scale- Total Score (ESS-TS)

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

    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.

  10. Mood

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

  11. Quality of Life: Calgary Sleep Apnea Quality of Life Index- Total Score (SAQLI-TS)

    Time frame: diagnostic visit (baseline)

    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.

Other outcomes

  1. Functional Magnetic Resonance Imaging (fMRI)

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

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

APPLES: Apnea Positive Pressure Long-Term Efficacy Study

Acronym: APPLES

Important dates

Study start
2002
Primary completion
2008
Study completion
2008
First posted
Jan 13, 2003
Registry last updated
Nov 28, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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