Trial Outcomes & Findings for Obstructive Sleep Apnea and Neurocognitive and Cardiovascular Function in Children With Down Syndrome (NCT NCT01808508)

Results Overview

The primary aim of the study is to assess the relationship between obstructive sleep apnea syndrome (OSAS) and the neurocognitive and behavioral outcomes of individuals with Down syndrome. Sleepiness was assessed using the pediatric version of the Epworth Sleepiness Scale (ESS). The ESS is a self-administered questionnaire with 8 questions. It provides a measure of a person's general level of daytime sleepiness, or average sleep propensity in daily life. The ESS asks people to rate, on a 4-point scale (0, low to 3, high) their usual chances of dozing off or falling asleep in 8 different situations or activities that most people engage in as part of their daily lives. The total ESS score provides an estimate of a general characteristic of each person's average level of sleepiness in daily life (0= no chance of dozing/no daytime sleepiness to 24=high chance of dozing/lots of daytime sleepiness).

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

27 participants

Primary outcome timeframe

4 Months

Results posted on

2016-02-08

Participant Flow

Children were recruited from The Children's Hospital of Philadelphia Trisomy 21 Program and community support groups.

27 subjects were consented, 4 subjects were ineligible before randomization. Subjects with an obstructive apnea hypopnea index (AHI) of at least 5/hr were randomized to CPAP or sham CPAP (Group 1 or 2) for 4 months in a double-blind fashion. Subjects with normal baseline polysomnograms (AHI \<1.5/hr) were followed without CPAP (Group 3).

Participant milestones

Participant milestones
Measure	Group 1- Continuous Positive Airway Pressure (CPAP) Group 1 will receive therapeutic CPAP for 4 months. Continuous positive airway pressure: Continuous positive airway pressure is a machine used with sleep which compresses air delivered via a nasal mask and thus helps stent the airway open.	Group 2-Sham Continuous Positive Airway Pressure (CPAP) Group 2 are individuals with OSAS who will receive sham or placebo continuous positive airway pressure (CPAP) for 4 months. Sham or placebo continuous positive airway pressure: Sham or placebo CPAP is a machine used instead of therapeutic CPAP. This machine is similar to a therapeutic CPAP machine but has built in leaks and does not deliver pressure. It is not effective in treating OSAS.	Group 3- No Intervention Group 3 are individuals with normal breathing during sleep who will not receive any intervention and will be used as a control group.
Overall Study STARTED	11	9	3
Overall Study COMPLETED	10	9	3
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1- Continuous Positive Airway Pressure (CPAP) Group 1 will receive therapeutic CPAP for 4 months. Continuous positive airway pressure: Continuous positive airway pressure is a machine used with sleep which compresses air delivered via a nasal mask and thus helps stent the airway open.	Group 2-Sham Continuous Positive Airway Pressure (CPAP) Group 2 are individuals with OSAS who will receive sham or placebo continuous positive airway pressure (CPAP) for 4 months. Sham or placebo continuous positive airway pressure: Sham or placebo CPAP is a machine used instead of therapeutic CPAP. This machine is similar to a therapeutic CPAP machine but has built in leaks and does not deliver pressure. It is not effective in treating OSAS.	Group 3- No Intervention Group 3 are individuals with normal breathing during sleep who will not receive any intervention and will be used as a control group.
Overall Study Lost to Follow-up	1	0	0

Baseline Characteristics

Obstructive Sleep Apnea and Neurocognitive and Cardiovascular Function in Children With Down Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1- Continuous Positive Airway Pressure (CPAP) n=11 Participants Group 1 will receive therapeutic CPAP for 4 months. Continuous positive airway pressure: Continuous positive airway pressure is a machine used with sleep which compresses air delivered via a nasal mask and thus helps stent the airway open.	Group 2-Sham Continuous Positive Airway Pressure (CPAP) n=9 Participants Group 2 are individuals with OSAS who will receive sham or placebo continuous positive airway pressure (CPAP) for 4 months. Sham or placebo continuous positive airway pressure: Sham or placebo CPAP is a machine used instead of therapeutic CPAP. This machine is similar to a therapeutic CPAP machine but has built in leaks and does not deliver pressure. It is not effective in treating OSAS.	Group 3 - No Intervention n=3 Participants Group 3 are individuals with normal breathing during sleep who will not receive any intervention and will be used as a control group	Total n=23 Participants Total of all reporting groups
Age, Continuous	10.0 years n=5 Participants	12.0 years n=7 Participants	12 years n=5 Participants	10 years n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	14 Participants n=4 Participants
Region of Enrollment United States	11 participants n=5 Participants	9 participants n=7 Participants	3 participants n=5 Participants	23 participants n=4 Participants

PRIMARY outcome

Timeframe: 4 Months

Population: 1 OSAS subject randomized to CPAP did not return for follow-up

The primary aim of the study is to assess the relationship between obstructive sleep apnea syndrome (OSAS) and the neurocognitive and behavioral outcomes of individuals with Down syndrome. Sleepiness was assessed using the pediatric version of the Epworth Sleepiness Scale (ESS). The ESS is a self-administered questionnaire with 8 questions. It provides a measure of a person's general level of daytime sleepiness, or average sleep propensity in daily life. The ESS asks people to rate, on a 4-point scale (0, low to 3, high) their usual chances of dozing off or falling asleep in 8 different situations or activities that most people engage in as part of their daily lives. The total ESS score provides an estimate of a general characteristic of each person's average level of sleepiness in daily life (0= no chance of dozing/no daytime sleepiness to 24=high chance of dozing/lots of daytime sleepiness).

Outcome measures

Outcome measures
Measure	Group 1- Continuous Positive Airway Pressure (CPAP) n=10 Participants Group 1 will receive therapeutic CPAP for 4 months. Continuous positive airway pressure: Continuous positive airway pressure is a machine used with sleep which compresses air delivered via a nasal mask and thus helps stent the airway open.	Group 2-Sham Continuous Positive Airway Pressure (CPAP) n=9 Participants Group 2 are individuals with OSAS who will receive sham or placebo continuous positive airway pressure (CPAP) for 4 months. Sham or placebo continuous positive airway pressure: Sham or placebo CPAP is a machine used instead of therapeutic CPAP. This machine is similar to a therapeutic CPAP machine but has built in leaks and does not deliver pressure. It is not effective in treating OSAS.	Group 3- No Intervention n=3 Participants Group 3 are individuals with normal breathing during sleep who will not receive any intervention and will be used as a control group.
Change in Epworth Sleepiness Scale From Baseline to End of Study	-1 units on a scale Interval -4.0 to 0.0	-0.5 units on a scale Interval -3.0 to 0.75	1 units on a scale Interval 0.5 to 3.5

SECONDARY outcome

Timeframe: 4 Months

Population: 1 OSAS subject randomized to CPAP did not return for follow-up

The change in behavioral domain was measured by the Child Check Behavior List. The CBCL is a widely used method of identifying problem behavior in children. Problems are identified by a respondent who knows the child well, usually a parent or other care giver. There are 2 versions based on the child's age (CBCL/1½-5 for use children 18 months-5 years; the CBCL/6-18 for children aged 6-18 years). The checklists consists of a number of statements about the child's behavior and responses are recorded on a scale: 0 = Not True, 1 = Somewhat or Sometimes True, 2 = Very True or Often True. The preschool checklist contains 100 questions and, school-age checklist contains 120 questions. 8 sub-scores (1 for each of 8 syndromes: anxious/depressed, withdrawn depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior and aggressive behavior) are calculated, each ranging from 0 (normal) to 16 (clinical behavior).

Outcome measures

Outcome measures
Measure	Group 1- Continuous Positive Airway Pressure (CPAP) n=10 Participants Group 1 will receive therapeutic CPAP for 4 months. Continuous positive airway pressure: Continuous positive airway pressure is a machine used with sleep which compresses air delivered via a nasal mask and thus helps stent the airway open.	Group 2-Sham Continuous Positive Airway Pressure (CPAP) n=9 Participants Group 2 are individuals with OSAS who will receive sham or placebo continuous positive airway pressure (CPAP) for 4 months. Sham or placebo continuous positive airway pressure: Sham or placebo CPAP is a machine used instead of therapeutic CPAP. This machine is similar to a therapeutic CPAP machine but has built in leaks and does not deliver pressure. It is not effective in treating OSAS.	Group 3- No Intervention n=3 Participants Group 3 are individuals with normal breathing during sleep who will not receive any intervention and will be used as a control group.
Change in Child Behavior Checklist (CBCL) Total Score From Baseline to 4 Months	-2 units on a scale Interval -4.5 to 0.0	2 units on a scale Interval 0.75 to 5.25	2 units on a scale Interval 1.0 to 4.5

SECONDARY outcome

Timeframe: 4 Months

Population: 1 OSAS subject randomized to CPAP did not return for follow-up

The change in left ventricular mass index score, measured on echocardiography, was used to assess the relationship between obstructive sleep apnea syndrome and cardiovascular function of individuals with Down syndrome. Left ventricular (LV) mass was calculated from M-mode measurements of the LV end-diastolic dimension, the thickness of the interventricular septum and the thickness of the LV posterior wall, and presented as a z-score.

Outcome measures

Outcome measures
Measure	Group 1- Continuous Positive Airway Pressure (CPAP) n=10 Participants Group 1 will receive therapeutic CPAP for 4 months. Continuous positive airway pressure: Continuous positive airway pressure is a machine used with sleep which compresses air delivered via a nasal mask and thus helps stent the airway open.	Group 2-Sham Continuous Positive Airway Pressure (CPAP) n=9 Participants Group 2 are individuals with OSAS who will receive sham or placebo continuous positive airway pressure (CPAP) for 4 months. Sham or placebo continuous positive airway pressure: Sham or placebo CPAP is a machine used instead of therapeutic CPAP. This machine is similar to a therapeutic CPAP machine but has built in leaks and does not deliver pressure. It is not effective in treating OSAS.	Group 3- No Intervention n=3 Participants Group 3 are individuals with normal breathing during sleep who will not receive any intervention and will be used as a control group.
Change in the Left Ventricular (LV) Mass Index Score From Baseline to 4 Months	-0.06 z-score Interval -0.58 to 1.57	-1.18 z-score Interval -1.97 to 0.0	0.36 z-score Interval 0.12 to 2.71

SECONDARY outcome

Timeframe: 4 Months

Population: The majority of subjects were unable to follow instructions properly and therefore none could successfully complete the test. Thus the results were not considered to be valid.

As secondary outcome of the second aim, we will use the distance walked during the 6 minute walk test.

Outcome measures

Outcome data not reported

Adverse Events

Group 1- Continuous Positive Airway Pressure (CPAP)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Group 2-Sham Continuous Positive Airway Pressure (CPAP)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Group 3- No Intervention

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Group 1- Continuous Positive Airway Pressure (CPAP) n=11 participants at risk Group 1 will receive therapeutic CPAP for 4 months. Continuous positive airway pressure: Continuous positive airway pressure is a machine used with sleep which compresses air delivered via a nasal mask and thus helps stent the airway open.	Group 2-Sham Continuous Positive Airway Pressure (CPAP) n=9 participants at risk Group 2 are individuals with OSAS who will receive sham or placebo continuous positive airway pressure (CPAP) for 4 months. Sham or placebo continuous positive airway pressure: Sham or placebo CPAP is a machine used instead of therapeutic CPAP. This machine is similar to a therapeutic CPAP machine but has built in leaks and does not deliver pressure. It is not effective in treating OSAS.	Group 3- No Intervention n=3 participants at risk Group 3 are individuals with normal breathing during sleep who will not receive any intervention and will be used as a control group.
Skin and subcutaneous tissue disorders Pressure Sore	9.1% 1/11 • Number of events 1 • 4 Months	0.00% 0/9 • 4 Months	33.3% 1/3 • Number of events 1 • 4 Months
Gastrointestinal disorders Abdominal Pain	0.00% 0/11 • 4 Months	11.1% 1/9 • Number of events 1 • 4 Months	0.00% 0/3 • 4 Months
Infections and infestations Lyme Disease	0.00% 0/11 • 4 Months	11.1% 1/9 • Number of events 1 • 4 Months	0.00% 0/3 • 4 Months

Additional Information

Carole L. Marcus, MBBCh

Children's Hospital of Philadelphia

Phone: 267-426-5842

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place