Trial Outcomes & Findings for Cerebral Blood Flow and Childhood Obstructive Sleep Apnea (NCT NCT02995837)

NCT ID: NCT02995837

Last Updated: 2024-07-09

Results Overview

To determine whether children with OSAS have impaired blood flow regulation elicited by hypercapneic challenge compared to normal controls at baseline.

• Recruitment status: COMPLETED
• Target enrollment: 47 participants
• Primary outcome timeframe: Baseline measurements, up to 24 hours
• Results posted on: 2024-07-09

Participant Flow

Recruitment occurred between October 2016 and February 2020. Participants with obstructive sleep apnea were recruited from the Children's Hospital of Philadelphia Sleep Center. Control participants were recruited by means of advertisement.

Screening phase based on the Adaptive Behavior Assessment System 3 (ABAS 3) and sleep study results resulted in 13 screen failures.

Participant milestones

Measure	Obstructive Sleep Apnea Syndrome (OSAS) \- Typically developing children aged 6-12 years with no history of upper airway surgery or previous treatment of obstructive sleep apnea, with an obstructive apnea hypopnea index equal to or greater than 5 events per hour.	Controls \- Typically developing children aged 6-12 years with no snoring and no history of previous sleep disordered breathing, and an obstructive apnea hypopnea index ≤1.5/hour.
Overall Study STARTED	19	15
Overall Study COMPLETED	10	7
Overall Study NOT COMPLETED	9	8

Reasons for withdrawal

Measure	Obstructive Sleep Apnea Syndrome (OSAS) \- Typically developing children aged 6-12 years with no history of upper airway surgery or previous treatment of obstructive sleep apnea, with an obstructive apnea hypopnea index equal to or greater than 5 events per hour.	Controls \- Typically developing children aged 6-12 years with no snoring and no history of previous sleep disordered breathing, and an obstructive apnea hypopnea index ≤1.5/hour.
Overall Study Lost to Follow-up	9	8

Baseline Characteristics

Cerebral Blood Flow and Childhood Obstructive Sleep Apnea

Baseline characteristics by cohort

Measure	Obstructive Sleep Apnea Syndrome (OSAS) n=18 Participants \- Typically developing children aged 6-12 years with no history of upper airway surgery or previous treatment of obstructive sleep apnea, with an obstructive apnea hypopnea index equal to or greater than 5 events per hour.	Controls n=14 Participants \- Typically developing children aged 6-12 years with no snoring and no history of previous sleep disordered breathing, and an obstructive apnea hypopnea index ≤1.5/hour.	Total n=32 Participants Total of all reporting groups
Age, Continuous	9.8 years STANDARD_DEVIATION 3.4 • n=5 Participants	10.3 years STANDARD_DEVIATION 3 • n=7 Participants	9.81 years STANDARD_DEVIATION 1.77 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	12 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants	14 participants n=7 Participants	32 participants n=5 Participants
Apnea hypopnea index, N/hour	16.5 events per hour STANDARD_DEVIATION 11.9 • n=5 Participants	0.74 events per hour STANDARD_DEVIATION 0.44 • n=7 Participants	9.6 events per hour STANDARD_DEVIATION 11.9 • n=5 Participants
Body mass index z-score	1.87 Z-score STANDARD_DEVIATION 1.57 • n=5 Participants	-0.04 Z-score STANDARD_DEVIATION 1.52 • n=7 Participants	0.91 Z-score STANDARD_DEVIATION 1.96 • n=5 Participants
Oxyhemoglobin saturation nadir during sleep, %	83.5 percentage of oxyhemoglobin STANDARD_DEVIATION 12 • n=5 Participants	91.5 percentage of oxyhemoglobin STANDARD_DEVIATION 6 • n=7 Participants	86.7 percentage of oxyhemoglobin STANDARD_DEVIATION 7.1 • n=5 Participants
Time with oxyhemoglobin saturation < 90%	1.1 % of total sleep time STANDARD_DEVIATION 1.4 • n=5 Participants	0.02 % of total sleep time STANDARD_DEVIATION 0.06 • n=7 Participants	0.6 % of total sleep time STANDARD_DEVIATION 1.2 • n=5 Participants
Sleep duration	84.0 % of total sleep time STANDARD_DEVIATION 11.8 • n=5 Participants	85.6 % of total sleep time STANDARD_DEVIATION 7.3 • n=7 Participants	84.7 % of total sleep time STANDARD_DEVIATION 10 • n=5 Participants
Stage N1	4.81 % of total sleep time STANDARD_DEVIATION 4.62 • n=5 Participants	1.31 % of total sleep time STANDARD_DEVIATION 3.68 • n=7 Participants	4.5 % of total sleep time STANDARD_DEVIATION 4.9 • n=5 Participants
Stage N2	46.1 % of total sleep time STANDARD_DEVIATION 5.1 • n=5 Participants	44.4 % of total sleep time STANDARD_DEVIATION 7.9 • n=7 Participants	44.4 % of total sleep time STANDARD_DEVIATION 6.1 • n=5 Participants
Stage N3	29.05 % of total sleep time STANDARD_DEVIATION 9.9 • n=5 Participants	31 % of total sleep time STANDARD_DEVIATION 5 • n=7 Participants	31 % of total sleep time STANDARD_DEVIATION 7.6 • n=5 Participants
Stage Rapid Eye Movement	18.6 % of total sleep time STANDARD_DEVIATION 8.39 • n=5 Participants	22.7 % of total sleep time STANDARD_DEVIATION 5.17 • n=7 Participants	20.3 % of total sleep time STANDARD_DEVIATION 5.4 • n=5 Participants
Sleep arousal	13.08 Arousals per hour STANDARD_DEVIATION 11.91 • n=5 Participants	7.84 Arousals per hour STANDARD_DEVIATION 3.28 • n=7 Participants	12.9 Arousals per hour STANDARD_DEVIATION 9.2 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline measurements, up to 24 hours

Population: Percentage of change from baseline of cerebral blood flow during hypercapneic challenge is reported in children with OSAS and controls. Unit is % change from baseline within the groups.

To determine whether children with OSAS have impaired blood flow regulation elicited by hypercapneic challenge compared to normal controls at baseline.

Outcome measures

Measure	Obstructive Sleep Apnea Syndrome (OSAS) n=18 Participants \- Typically developing children aged 6-12 years with no history of upper airway surgery or previous treatment of obstructive sleep apnea, with an obstructive apnea hypopnea index equal to or greater than 5 events per hour.	Controls n=14 Participants \- Typically developing children aged 6-12 years with no snoring and no history of previous sleep disordered breathing, and an obstructive apnea hypopnea index ≤1.5/hour.
Change in Cerebral Blood Flow (CBF) at Baseline Between Obstructive Sleep Apnea Syndrome (OSAS) and Controls	184 percentage of change from baseline Standard Deviation 56	209 percentage of change from baseline Standard Deviation 109

SECONDARY outcome

Timeframe: Up to 12 Months

Population: Only children who completed 2 or more repeated measurements were included in the analysis.

Only children who completed 2 or more repeated measurements were included in the analysis. The change in CBF measurements obtained at baseline when compared at 6 and 12 months after baseline for controls and after adenotonsillectomy for OSAS subjects. The slope of the change in CBF over time is reported: Delta CBF/Delta time, units= percentage over year. Minimum values are -100, maximum values +100, positive values mean better outcome.Cerebral blood flow were measured non-invasively while the child was breathing oxygen mixed with carbon dioxide.

Outcome measures

Measure	Obstructive Sleep Apnea Syndrome (OSAS) n=12 Participants \- Typically developing children aged 6-12 years with no history of upper airway surgery or previous treatment of obstructive sleep apnea, with an obstructive apnea hypopnea index equal to or greater than 5 events per hour.	Controls n=9 Participants \- Typically developing children aged 6-12 years with no snoring and no history of previous sleep disordered breathing, and an obstructive apnea hypopnea index ≤1.5/hour.
Comparison of the Change in CBF From Baseline to Study Completion Between OSAS and Control Subjects	0.013 percentage change per year Standard Deviation 0.04	-0.083 percentage change per year Standard Deviation 0.17

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 months

Population: Correlation coefficients between the obstructive apnea hypopnea index and relative change of cerebral blood flow were calculated

Children who completed baseline measurements were included. Correlation coefficients between the obstructive apnea hypopnea index and relative change of cerebral blood flow in children with obstructive sleep apnea and Controls are reported.

The Correlation Coefficient is calculated by dividing the Covariance of the apnea hypopnea index and CBF by the Standard deviation of the apnea hypopnea index and CBF. Units of the standard deviation of CBF= unit of CBF. So, in the correlation coefficient formula, units get canceled. The correlation coefficient does not have any units and can be positive or negative. In this case positive correlation coefficients signal better regulation of CBF.

Outcome measures

Measure	Obstructive Sleep Apnea Syndrome (OSAS) n=18 Participants \- Typically developing children aged 6-12 years with no history of upper airway surgery or previous treatment of obstructive sleep apnea, with an obstructive apnea hypopnea index equal to or greater than 5 events per hour.	Controls n=14 Participants \- Typically developing children aged 6-12 years with no snoring and no history of previous sleep disordered breathing, and an obstructive apnea hypopnea index ≤1.5/hour.
Association Between CBF Regulation and Severity of OSAS	-0.0018 Correlation coefficients	0.37 Correlation coefficients

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline

Population: Only children who completed the Behavior Rating Inventory of Executive Function testing were included in the analysis

Children who completed baseline measurements were included. One child in the obstructive sleep apnea arm did not complete the Behavior Rating Inventory of Executive Function testing.

Behavior Rating Inventory of Executive Function (global executive functioning T score) is reported between the 2 groups. Because this measures uses a T score, a score of 50 is considered average for the population. The scale is 0-100, with higher scores signaling executive functioning impairment. T-scores of 60-64 are in the mildly elevated range, and scores equal to or exceeding 65 are considered to be significantly elevated. The typical standard deviation (SD) observed is 10.

Outcome measures

Measure	Obstructive Sleep Apnea Syndrome (OSAS) n=17 Participants \- Typically developing children aged 6-12 years with no history of upper airway surgery or previous treatment of obstructive sleep apnea, with an obstructive apnea hypopnea index equal to or greater than 5 events per hour.	Controls n=13 Participants \- Typically developing children aged 6-12 years with no snoring and no history of previous sleep disordered breathing, and an obstructive apnea hypopnea index ≤1.5/hour.
Behavior Rating Inventory of Executive Function Global Executive Functioning T-score	56.5 T score Standard Deviation 14.1	49.7 T score Standard Deviation 11.1

Adverse Events

Obstructive Sleep Apnea Syndrome (OSAS)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Ignacio Tapia, MD

University of Miami

Phone: 3052439885

Email: itapia@miami.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place