Attention Deficit Disorder With Hyperactivity, Child Behavior Disorders, Disorders of Excessive Somnolence, Sleep Apnea, Obstructive, Sleep Apnea Syndromes
Conditions
Keywords
polysomnography, child, continuous positive airway pressure, tonsillectomy, neuropsychological tests, cognition, sleepiness, behavior
Brief summary
Obstructive sleep-disordered breathing (SDB) affects 2-3% of children and may lead to problems with nighttime sleep and daytime behavior, learning, sleepiness, and mood. Adenotonsillectomy (AT) is the second most common surgical procedure in children. It is now performed more often for suspected SDB than for any other indication. However, recent studies indicate that many if not most children still have SDB after AT, and many still have learning or behavioral problems associated with SDB. The goals of this study are: (1) to assess the extent that behavior, cognition, and sleepiness in children can improve with Continuous positive airway pressure (CPAP) treatment after AT, and (2) to identify which patients stand to gain most from post-operative assessment and treatment.
Detailed description
Obstructive sleep-disordered breathing (SDB) affects at least 2-3% of children and may have substantial adverse impact on behavior and cognition. Adenotonsillectomy (AT), the second most common surgical procedure in children, is now performed more often for suspected SDB than for any other indication. However, recent studies among an increasingly obese population now show something alarming: many if not most children still have SDB after AT, and many still suffer from residual neurobehavioral morbidity. Furthermore, the investigators' ongoing, 12-year, NIH-funded research has shown that standard preoperative polysomnographic measures of SDB do not consistently predict post-AT improvement in behavior and cognition. This may arise in part because many children after AT still have SDB, and because linear relationships between standard SDB measures and neurobehavioral morbidity may not exist. Even at subtle levels, SDB may promote significant neurobehavioral morbidity. Some have suggested that polysomnography may be more important after AT than before AT. However, in practice few children receive polysomnography before AT, and even fewer after AT, when continuous positive airway pressure (CPAP) could still provide definitive relief from SDB. Preliminary data from our group suggest that CPAP after AT is well-tolerated by most children and may provide significant benefit. However, virtually no published evidence exists to address critical clinical questions: which children benefit most from CPAP after AT; what role can clinical symptoms or polysomnography play in that determination; and what neurobehavioral gains are achieved by CPAP after AT? The investigators therefore will undertake a highly practical, clinical study with two main goals: (1) to assess the extent that behavior, cognition, and sleepiness in children can improve with CPAP after AT, and (2) to identify which patients stand to gain most from post-operative assessment and treatment. This research will use reversible SDB-related neurobehavioral morbidity as the criteria by which to judge the utility of clinical symptoms and polysomnography in identification of candidates for CPAP after AT.
Interventions
PROCEDURECPAP treatment
6 months of treatment with PAP (CPAP or BPAP)
OTHERNo CPAP treatment
Children randomized to the comparison group will receive routine care
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Michigan Technological University
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Children ages 5-12 years old, 2. Scheduled for an adenotonsillectomy for treatment of sleep apnea, 3. Child must provide assent, and 4. Parent or legal guardian must be able to speak and read English, and agree to the study.
Exclusion criteria
1. No siblings of children already enrolled in the study, 2. Children who expect to have another surgery (in addition to AT) during the period of participation in this study, 3. Neurological, psychiatric, or medical conditions, or social factors that may affect test results, prevent children from returning for required study visits, or interfere with the study treatment, or 4. Certain medications that affect sleepiness or alertness, for example: * Stimulants (such as Ritalin, Adderall, or Concerta), * Sleep aides (such as Melatonin, Ambien, or Ativan), or * Sedating medicines (such as Benadryl, Klonopin, Xanax, or Valerian).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Behavioral Index After 6 Months of CPAP or No-CPAP | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP | The sum of the T-scores of The Conners' Parent Rating Scales (CPRS-R:L, ADHD index) and the Child Behavior Checklist (CBCL, Attention Deficit/Hyperactivity Problems) are used to construct the primary study outcome measure Behavioral Index. Behavioral index is a T score (adjusted for age and gender) with a range of \<10 to \>90 - where higher scores mean worse behavior and lower scores mean better behavior, so a negative change score represents an improvement in behavior. T-scores with a mean of 50 and SD of 10 are computed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cognition as Shown by NIH Toolbox Composite Score | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP | Scores are reported as standardized scores with a mean of 100 and SD of 15. Minimum value 40 and Maximum value 160. Higher scores are better |
| Change in Sleepiness as Measured by Epworth Sleepiness Scale | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP | Epworth Sleepiness Scale scores range from 0 to 24 where higher scores mean greater sleepiness. |
| Change in Sleepiness After AT as Measured by Multiple Sleep Latency Test (MSLT) | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP | Multiple Sleep Latency Test (MSLT) is an objective measure of sleepiness determined by measure of brain waves and other physiological signals over a 30 minute period. This is measured for five 30 minute periods across the day and average latency to sleep for each participant across those times were used to calculate the mean sleep latency. The score is measured in how quickly one would fall asleep, measured in minutes, so a negative number of minutes in the change score means that participants fell asleep more quickly than previously. |
| Change in Quality of Life as Measured by Peds QL | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP | Peds-QL is a quality of life symptom measurement with a score range of 0 to 100. Higher scores are better quality of life |
| CPAP Adherence as Measured by Number of Participants Who Used the CPAP Consistently. | Starting at 4 months after AT and continuing through 10 months after AT | CPAP adherence data will be downloaded from CPAP machines. It is defined for this study as using the CPAP machine for at least an average of 4 hours per night during the last 60 days of the assignment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Cognition as Measured by Fluid Cognition Scores | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP | Scores are reported as standardized scores with a mean of 100 and SD of 15. Minimum value 40, Maximum value 160. Higher scores are better |
| Change in Cognition After AT as Shown by Academic Achievement | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP | Academic achievement mean score is a standardized score with a mean of 100 and SD 15. Minimum value 40 and Maximum value 160. Higher scores are better |
Countries
United States
Participant flow
Recruitment details
Of 120 consented, 105 were randomized to CPAP or control. (Of the 15 who weren't randomized, 8 were lost to follow up; the other withdrew for various reasons)
Participants by arm
| Arm | Count |
|---|---|
| Control Group (Surgery Only - no CPAP) The participants who were not assigned to CPAP | 34 |
| CPAP After Surgery (Adherent) Those participants assigned to CPAP who had at least 4 hours of electronically recorded CPAP use per night | 38 |
| CPAP After Surgery (Non-adherent) Those participants assigned CPAP who did not have at least 4 hours of electronically recorded CPAP use per night. | 33 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 4 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Total | Control Group (Surgery Only - no CPAP) | CPAP After Surgery (Adherent) | CPAP After Surgery (Non-adherent) |
|---|---|---|---|---|
| Academic Achievement Score | 104.6 units on a scale STANDARD_DEVIATION 13.1 | 104.1 units on a scale STANDARD_DEVIATION 13.4 | 107.2 units on a scale STANDARD_DEVIATION 14.6 | 102.1 units on a scale STANDARD_DEVIATION 10.7 |
| Age, Continuous | 8.1 years STANDARD_DEVIATION 2.1 | 7.9 years STANDARD_DEVIATION 2 | 8.3 years STANDARD_DEVIATION 2.2 | 8.0 years STANDARD_DEVIATION 2 |
| (Apnea-Hypopnea Index (AHI) | 2.2 events/hour STANDARD_DEVIATION 1.9 | 2.4 events/hour STANDARD_DEVIATION 2 | 2.2 events/hour STANDARD_DEVIATION 1.7 | 2.1 events/hour STANDARD_DEVIATION 2 |
| Behavioral Index | 58.5 units on a scale (T-Score) STANDARD_DEVIATION 12.1 | 61.6 units on a scale (T-Score) STANDARD_DEVIATION 13.4 | 56.5 units on a scale (T-Score) STANDARD_DEVIATION 11.3 | 57.8 units on a scale (T-Score) STANDARD_DEVIATION 11.6 |
| Epworth Sleepiness Scale | 6.8 units on a scale STANDARD_DEVIATION 3.9 | 7.2 units on a scale STANDARD_DEVIATION 4.6 | 6.9 units on a scale STANDARD_DEVIATION 3.9 | 6.4 units on a scale STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 5 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 98 Participants | 29 Participants | 36 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fluid Cognition Composite Age Adjusted score | 95.8 units on a scale STANDARD_DEVIATION 13.1 | 97.3 units on a scale STANDARD_DEVIATION 13.2 | 96 units on a scale STANDARD_DEVIATION 14.2 | 93.9 units on a scale STANDARD_DEVIATION 11.6 |
| Multiple Sleep Latency Test (MSLT) | 25.0 minutes STANDARD_DEVIATION 5.3 | 24.7 minutes STANDARD_DEVIATION 6 | 25.9 minutes STANDARD_DEVIATION 4.6 | 24.4 minutes STANDARD_DEVIATION 5.4 |
| NIH Toolbox Age adjusted composite score | 95.1 units on a scale STANDARD_DEVIATION 11.6 | 95.7 units on a scale STANDARD_DEVIATION 11.9 | 96.2 units on a scale STANDARD_DEVIATION 12.3 | 93.9 units on a scale STANDARD_DEVIATION 11.6 |
| Quality of Life | 78.1 units on a scale STANDARD_DEVIATION 14.9 | 78.2 units on a scale STANDARD_DEVIATION 13.7 | 78.7 units on a scale STANDARD_DEVIATION 16 | 77.3 units on a scale STANDARD_DEVIATION 17.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 1 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 12 Participants | 4 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 76 Participants | 28 Participants | 29 Participants | 19 Participants |
| Region of Enrollment United States | 105 Participants | 34 Participants | 38 Participants | 33 Participants |
| Sex: Female, Male Female | 50 Participants | 13 Participants | 21 Participants | 16 Participants |
| Sex: Female, Male Male | 55 Participants | 21 Participants | 17 Participants | 17 Participants |
| Sleep Related Breathing Disturbances (SBRD) sub-scale of Pediatric Sleep Questionnaire | 0.35 Ratio STANDARD_DEVIATION 0.21 | 0.36 Ratio STANDARD_DEVIATION 0.24 | 0.32 Ratio STANDARD_DEVIATION 0.21 | 0.37 Ratio STANDARD_DEVIATION 0.17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 36 | 0 / 15 |
| other Total, other adverse events | 59 / 69 | 26 / 36 | 7 / 15 |
| serious Total, serious adverse events | 6 / 69 | 7 / 36 | 4 / 15 |
Outcome results
Primary
Change in Behavioral Index After 6 Months of CPAP or No-CPAP
The sum of the T-scores of The Conners' Parent Rating Scales (CPRS-R:L, ADHD index) and the Child Behavior Checklist (CBCL, Attention Deficit/Hyperactivity Problems) are used to construct the primary study outcome measure Behavioral Index. Behavioral index is a T score (adjusted for age and gender) with a range of \<10 to \>90 - where higher scores mean worse behavior and lower scores mean better behavior, so a negative change score represents an improvement in behavior. T-scores with a mean of 50 and SD of 10 are computed.
Time frame: assessed as change from baseline to 6 months of CPAP therapy or no-CPAP
Population: Data for two participants in the control group are not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group (Surgery Only - no CPAP) | Change in Behavioral Index After 6 Months of CPAP or No-CPAP | -2.7 T score | Standard Deviation 5.8 |
| CPAP After Surgery (Non-adherent) | Change in Behavioral Index After 6 Months of CPAP or No-CPAP | .9 T score | Standard Deviation 4.8 |
| CPAP After Surgery (Adherent) | Change in Behavioral Index After 6 Months of CPAP or No-CPAP | -1.2 T score | Standard Deviation 6.3 |
Comparison: Intent to treat for controls vs. treatment (adherent/non-adherent)p-value: 0.07t-test, 2 sided
Secondary
Change in Cognition as Shown by NIH Toolbox Composite Score
Scores are reported as standardized scores with a mean of 100 and SD of 15. Minimum value 40 and Maximum value 160. Higher scores are better
Time frame: assessed as change from baseline to 6 months of CPAP therapy or no-CPAP
Population: Lower numbers of participants analyzed are shown here because the tool is not appropriate for younger children
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group (Surgery Only - no CPAP) | Change in Cognition as Shown by NIH Toolbox Composite Score | 5.5 score on a scale | Standard Deviation 9.5 |
| CPAP After Surgery (Non-adherent) | Change in Cognition as Shown by NIH Toolbox Composite Score | 2.8 score on a scale | Standard Deviation 9.8 |
| CPAP After Surgery (Adherent) | Change in Cognition as Shown by NIH Toolbox Composite Score | 3.9 score on a scale | Standard Deviation 7.8 |
Comparison: Intent to treat for controls vs. treatment (adherent/non-adherent)p-value: 0.34t-test, 2 sided
Secondary
Change in Quality of Life as Measured by Peds QL
Peds-QL is a quality of life symptom measurement with a score range of 0 to 100. Higher scores are better quality of life
Time frame: assessed as change from baseline to 6 months of CPAP therapy or no-CPAP
Population: Data for one participant is not available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group (Surgery Only - no CPAP) | Change in Quality of Life as Measured by Peds QL | 4.1 score on a scale | Standard Deviation 9 |
| CPAP After Surgery (Non-adherent) | Change in Quality of Life as Measured by Peds QL | 0.5 score on a scale | Standard Deviation 10.2 |
| CPAP After Surgery (Adherent) | Change in Quality of Life as Measured by Peds QL | 2.4 score on a scale | Standard Deviation 12.1 |
Comparison: Intent to treat for controls vs. treatment (adherent/non-adherent)p-value: 0.25t-test, 2 sided
Secondary
Change in Sleepiness After AT as Measured by Multiple Sleep Latency Test (MSLT)
Multiple Sleep Latency Test (MSLT) is an objective measure of sleepiness determined by measure of brain waves and other physiological signals over a 30 minute period. This is measured for five 30 minute periods across the day and average latency to sleep for each participant across those times were used to calculate the mean sleep latency. The score is measured in how quickly one would fall asleep, measured in minutes, so a negative number of minutes in the change score means that participants fell asleep more quickly than previously.
Time frame: assessed as change from baseline to 6 months of CPAP therapy or no-CPAP
Population: Data for one participant are not available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group (Surgery Only - no CPAP) | Change in Sleepiness After AT as Measured by Multiple Sleep Latency Test (MSLT) | -1.8 minutes | Standard Deviation 4 |
| CPAP After Surgery (Non-adherent) | Change in Sleepiness After AT as Measured by Multiple Sleep Latency Test (MSLT) | -1.3 minutes | Standard Deviation 5.1 |
| CPAP After Surgery (Adherent) | Change in Sleepiness After AT as Measured by Multiple Sleep Latency Test (MSLT) | -1.1 minutes | Standard Deviation 4.3 |
Comparison: Intent to treat for controls vs. treatment (adherent/non-adherent)p-value: 0.5t-test, 2 sided
Secondary
Change in Sleepiness as Measured by Epworth Sleepiness Scale
Epworth Sleepiness Scale scores range from 0 to 24 where higher scores mean greater sleepiness.
Time frame: assessed as change from baseline to 6 months of CPAP therapy or no-CPAP
Population: Data for two participants are not available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group (Surgery Only - no CPAP) | Change in Sleepiness as Measured by Epworth Sleepiness Scale | -1.6 score on a scale | Standard Deviation 3.7 |
| CPAP After Surgery (Non-adherent) | Change in Sleepiness as Measured by Epworth Sleepiness Scale | -1.0 score on a scale | Standard Deviation 2.2 |
| CPAP After Surgery (Adherent) | Change in Sleepiness as Measured by Epworth Sleepiness Scale | -1.9 score on a scale | Standard Deviation 3.8 |
Comparison: Intent to treat for controls vs. treatment (adherent/non-adherent)p-value: 0.93t-test, 2 sided
Secondary
CPAP Adherence as Measured by Number of Participants Who Used the CPAP Consistently.
CPAP adherence data will be downloaded from CPAP machines. It is defined for this study as using the CPAP machine for at least an average of 4 hours per night during the last 60 days of the assignment.
Time frame: Starting at 4 months after AT and continuing through 10 months after AT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group (Surgery Only - no CPAP) | CPAP Adherence as Measured by Number of Participants Who Used the CPAP Consistently. | 38 Participants |
Other Pre-specified
Change in Cognition After AT as Shown by Academic Achievement
Academic achievement mean score is a standardized score with a mean of 100 and SD 15. Minimum value 40 and Maximum value 160. Higher scores are better
Time frame: assessed as change from baseline to 6 months of CPAP therapy or no-CPAP
Population: Data from two participants are not available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group (Surgery Only - no CPAP) | Change in Cognition After AT as Shown by Academic Achievement | -1.0 units on a scale | Standard Deviation 5.6 |
| CPAP After Surgery (Non-adherent) | Change in Cognition After AT as Shown by Academic Achievement | 1.1 units on a scale | Standard Deviation 4.7 |
| CPAP After Surgery (Adherent) | Change in Cognition After AT as Shown by Academic Achievement | -2.5 units on a scale | Standard Deviation 8.6 |
Other Pre-specified
Change in Cognition as Measured by Fluid Cognition Scores
Scores are reported as standardized scores with a mean of 100 and SD of 15. Minimum value 40, Maximum value 160. Higher scores are better
Time frame: assessed as change from baseline to 6 months of CPAP therapy or no-CPAP
Population: Lower numbers are shown here as the tool is not appropriate for younger children
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group (Surgery Only - no CPAP) | Change in Cognition as Measured by Fluid Cognition Scores | 6.7 score on a scale | Standard Deviation 12.4 |
| CPAP After Surgery (Non-adherent) | Change in Cognition as Measured by Fluid Cognition Scores | 1.7 score on a scale | Standard Deviation 11.5 |
| CPAP After Surgery (Adherent) | Change in Cognition as Measured by Fluid Cognition Scores | 3.4 score on a scale | Standard Deviation 10.1 |