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Obstructive Sleep Apnea in World Trade Center Responders

Obstructive Sleep Apnea in WTC Responders: Role of Nasal Pathology

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01753999
Enrollment
317
Registered
2012-12-21
Start date
2012-12-31
Completion date
2017-03-31
Last updated
2025-04-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obstructive Sleep Apnea

Keywords

World Trade Center (WTC), nasal symptoms, nasal inflammation, CPAP

Brief summary

The goal of the study is to examine the possible underlying causes of sleep apnea (a disorder in which there are problems with breathing during sleep) in World Trade Center Responders. The study will look at the relationship between sleep apnea and various nose and throat conditions. Specifically, the study will look at upper airway disease (problems with the nose and throat), nasal inflammation, and nasal resistance (the amount of airflow through the nose). Subjects will have a physical exam and answer questions about nasal symptoms and sleeping problems. Nasal lavage (washing the inner nasal passages) will be performed on the subjects and markers of inflammation will be measured in the lavage fluid. Rhinomanometry (measuring the airflow through the nose) will also be performed to measure the degree of airflow obstruction. All subjects will be asked to perform in-home sleep apnea monitoring. Those subjects who are diagnosed with sleep apnea will test two treatment methods. Sleep apnea is treated by using a CPAP (continuous positive airway pressure) device. This device blows air into a mask worn by the patient during sleep. The two treatment methods that will be tested are the fixed pressure CPAP (pressure is constant during use) and CPAP-flex (pressure decreases when the subject exhales). Patients will be randomly assigned to one treatment method for one month then crossed to the other treatment method for the next month. The investigators will determine if patients with certain nasal conditions (high nasal resistance) are more likely to use CPAP-flex rather than CPAP.

Detailed description

Following the World Trade Center (WTC) disaster, an estimated 40,000 individuals were exposed to significant amounts of dust while working in rescue, recovery and debris removal. A significant number of these responders have reported least one new or worsened upper airway respiratory symptom when examined in 2004 with 50% of responders continuing to have symptoms of chronic rhino-sinusitis or upper airway disease (UAD) in 2007. In addition, about 50% of those with UAD referred to our sleep center reported new onset snoring on their questionnaires immediately following their exposure and had unusually high prevalence of obstructive sleep apnea (OSA) that did not appear to be related to obesity, which is the usual risk factor for OSA. This suggests to us that mechanisms other than obesity may be important in the pathogenesis of OSA in these subjects. Given their chronic nasal symptoms they also provide a unique opportunity to examine the relationship between nasal pathology and OSA and test if nasal symptoms reported by the subjects in the WTC Health Program (WTCHP) are an indicator of increased nasal resistance due to nasal inflammation resulting from exposure to the WTC dust. Positive Airway Pressure (CPAP) is the standard therapy for OSA but despite its efficacy has poor adherence. Subjects with high nasal resistance (such as responders with UAD and OSA) may experience additional pressure during expiration at the upper airway resulting in greater difficulty in tolerating CPAP therapy than those who do not have high nasal resistance. Reduction of excess expiratory positive pressure by the modality known as Cflex™ during CPAP therapy (CPAPFlex) may improve comfort and adherence in these subjects without compromising CPAP efficacy. In the present proposal we will study responders enrolled at the Environmental and Occupational Health Sciences Institute of Robert Wood Johnson Medical School (RWJMS) and the NYU School of Medicine Clinical Center of Excellence at Bellevue Hospital

Interventions

Use of the REMstar Auto A-Flex in standard CPAP therapy mode

DEVICECPAP - Flex

Use of Philips Respironics REMstar Auto A-Flex in C-Flex mode

Sponsors

NYU Langone Health
CollaboratorOTHER
Rutgers, The State University of New Jersey
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes

Inclusion criteria

* Member of the World Trade Center Health Program at either the Environmental and Occupational Healthy Sciences Institute at Robert Wood Johnson Medical School in Piscataway, NJ, the New York University School of Medicine Clinical Center of Excellence at Bellevue Hospital in New York, NY, or the Icahn School of Medicine at Mount Sinai.

Exclusion criteria

* Gross skeletal alterations affecting the upper airway (nose and throat) * Unstable chronic medical conditions known to affect Obstructive Sleep Apnea (congestive heart failure, stroke) * Pregnancy or intent to become pregnant * Habitual snoring or diagnosis of obstructive sleep apnea prior to 9/11/2001.

Design outcomes

Primary

MeasureTime frameDescription
Adherence to CPAP Pre-crossover5 weeks after initiation of treatmentThe use (number of hours per night) will be compared between standard CPAP and CPAP flex. Results are based on the first treatment period only (pre-crossover).
Adherence to CPAP Overall Study9 weeks after initiation of treatmentThe use (number of hours per night) will be compared between standard CPAP and CPAP flex. Results are based on both periods.

Secondary

MeasureTime frameDescription
CPAP Efficacy5 weeks after initiation of treatmentEfficacy will be evaluated by measuring the residual apnea and hypopnea index (AHI) while on treatment. The efficacy of standard CPAP and CPAP-flex will be compared. Results are based on the first treatment period only (pre-crossover).

Other

MeasureTime frameDescription
Adherence to CPAP Overall Study, Subjects With High Nasal Resistance9 weeks after initiation of treatmentThe use (number of hours per night) will be compared between standard CPAP and CPAP flex for subjects with high total nasal resistance (logTNR\>0.8). The analysis is based on both periods.
Adherence to CPAP Overall Study, Subjects With Low Nasal Resistance9 weeks after initiation of treatmentThe use (number of hours per night) will be compared between standard CPAP and CPAP flex for subjects with low total nasal resistance (logTNR\<=0.8). The analysis is based on both periods.

Countries

United States

Participant flow

Recruitment details

Subjects were recruited between January 2013 and December 2016 at three World Trade Center Health Program Clinical Centers of Excellence (Rutgers University, Icahn School of Medicine at Mount Sinai, and New York University School of Medicine).

Pre-assignment details

Subjects without OSA were excluded from the trial.

Participants by arm

ArmCount
All Study Participants
Participants who were randomized to receive either standard CPAP or CPAP-Flex.
317
Total317

Withdrawals & dropouts

PeriodReasonFG000FG001
Period 1 - Initial AssignmentLost to Follow-up1827
Period 1 - Initial AssignmentPhysician Decision23
Period 1 - Initial AssignmentWithdrawal by Subject1920
Period 2 -Cross to Alternate ArmLost to Follow-up1317
Period 2 -Cross to Alternate ArmPhysician Decision11
Period 2 -Cross to Alternate ArmWithdrawal by Subject35

Baseline characteristics

CharacteristicAll Study Participants
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
29 Participants
Age, Categorical
Between 18 and 65 years
288 Participants
Age, Continuous53.29 years
STANDARD_DEVIATION 8.23
Apnea and Hypopnea Index (AHI4%)17.01 Events/hour
STANDARD_DEVIATION 14.42
Ethnicity (NIH/OMB)
Hispanic or Latino
45 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
264 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
8 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
12 Participants
Race (NIH/OMB)
Black or African American
32 Participants
Race (NIH/OMB)
More than one race
33 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
13 Participants
Race (NIH/OMB)
White
227 Participants
Sex: Female, Male
Female
35 Participants
Sex: Female, Male
Male
282 Participants
Total Nasal Resistance
High Nasal Resistance (LogTNR>0.8)
132 Participants
Total Nasal Resistance
Low Nasal Resistance (LogTNR<=0.8)
169 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 2670 / 278
other
Total, other adverse events
0 / 2670 / 278
serious
Total, serious adverse events
0 / 2670 / 278

Outcome results

Primary

Adherence to CPAP Overall Study

The use (number of hours per night) will be compared between standard CPAP and CPAP flex. Results are based on both periods.

Time frame: 9 weeks after initiation of treatment

Population: Subjects who received the allocated treatment (i.e., turned on the PAP device) in either the first treatment period or the second treatment period.

ArmMeasureValue (MEDIAN)
Standard CPAPAdherence to CPAP Overall Study1.03 Hours/night
CPAP-FlexAdherence to CPAP Overall Study0.8 Hours/night
Primary

Adherence to CPAP Pre-crossover

The use (number of hours per night) will be compared between standard CPAP and CPAP flex. Results are based on the first treatment period only (pre-crossover).

Time frame: 5 weeks after initiation of treatment

Population: Subjects who received the allocated treatment (i.e., turned on the PAP device). The difference between the number allocated and the number of analyzed is the result of some subjects (n=11 in CPAP and n=16 in C-Flex) who did not turn on the device despite taking it home. These were assumed to have NOT received the allocated treatment.

ArmMeasureValue (MEDIAN)
Standard CPAPAdherence to CPAP Pre-crossover1 Hours/night
CPAP-FlexAdherence to CPAP Pre-crossover0.89 Hours/night
Secondary

CPAP Efficacy

Efficacy will be evaluated by measuring the residual apnea and hypopnea index (AHI) while on treatment. The efficacy of standard CPAP and CPAP-flex will be compared. Results are based on the first treatment period only (pre-crossover).

Time frame: 5 weeks after initiation of treatment

Population: Subjects who received treatment (turned on the PAP device). An additional 48 subjects on CPAP and 53 on CPAP-FLex were not analyzed as an AHI could not be generated during the analysis period due to insufficient use.

ArmMeasureValue (MEAN)Dispersion
Standard CPAPCPAP Efficacy2.89 Events/hourStandard Deviation 3.06
CPAP-FlexCPAP Efficacy3.12 Events/hourStandard Deviation 2.95
Secondary

CPAP Efficacy

Efficacy will be evaluated by measuring the residual apnea and hypopnea index (AHI) while on treatment. The efficacy of standard CPAP and CPAP-flex will be compared. Results are based on both treatment periods.

Time frame: 9 weeks after initiation of treatment

Population: Subjects who received the allocated treatment (i.e., turned on the PAP device; N=239 for CPAP and N=249 for CPAP Flex). An additional 82 subjects on CPAP and 102 subjects on CPAP-Flex were not analyzed as an AHI could not be generated during the analysis period due to insufficient use.

ArmMeasureValue (MEAN)Dispersion
Standard CPAPCPAP Efficacy2.71 events/hourStandard Deviation 2.76
CPAP-FlexCPAP Efficacy2.94 events/hourStandard Deviation 2.65
Other Pre-specified

Adherence to CPAP Overall Study, Subjects With High Nasal Resistance

The use (number of hours per night) will be compared between standard CPAP and CPAP flex for subjects with high total nasal resistance (logTNR\>0.8). The analysis is based on both periods.

Time frame: 9 weeks after initiation of treatment

Population: Subjects with high total nasal resistance who received the allocated treatment (i.e., turned on the PAP device) in either the first treatment period or in the second treatment period.Total nasal resistance data are missing for 8 subjects.

ArmMeasureValue (MEAN)
Standard CPAPAdherence to CPAP Overall Study, Subjects With High Nasal Resistance2.08 Hours/night
CPAP-FlexAdherence to CPAP Overall Study, Subjects With High Nasal Resistance1.75 Hours/night
Other Pre-specified

Adherence to CPAP Overall Study, Subjects With Low Nasal Resistance

The use (number of hours per night) will be compared between standard CPAP and CPAP flex for subjects with low total nasal resistance (logTNR\<=0.8). The analysis is based on both periods.

Time frame: 9 weeks after initiation of treatment

Population: Subjects with low total nasal resistance who received the allocated treatment (i.e., turned on the PAP device) in either the first treatment period or in the second treatment period. Total nasal resistance data are missing for 8 subjects.

ArmMeasureValue (MEAN)
Standard CPAPAdherence to CPAP Overall Study, Subjects With Low Nasal Resistance1.81 Hours/night
CPAP-FlexAdherence to CPAP Overall Study, Subjects With Low Nasal Resistance1.55 Hours/night

Source: ClinicalTrials.gov · Data processed: Mar 4, 2026