Obstructive Sleep Apnea in World Trade Center Responders

• Sponsor: Rutgers, The State University of New Jersey (Other)
• Overall Status: Completed
• CT.gov ID: NCT01753999
• Collaborator: NYU Langone Health (Other)
• Enrollment: 317
• Locations: 3
• Arms: 2
• Actual Duration (Months): 51
• Patients Per Site: 105.7
• Patients Per Site Per Month: 2.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea	Device: Standard CPAP; Device: CPAP - Flex	N/A

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 317 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Obstructive Sleep Apnea in WTC Responders: Role of Nasal Pathology
• Actual Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: Mar 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard CPAP Use of a standard CPAP (continuous positive airway pressure) device with constant pressure for 4 weeks to improve breathing during sleep	Device: Standard CPAP; Use of the REMstar Auto A-Flex in standard CPAP therapy mode; Other Names: Philips Respironics REMstar Auto A-Flex
Active Comparator: CPAP - Flex Use of CPAP-Flex (continuous positive airway pressure) device with decreased pressure during expiration for 4 weeks to improve breathing during sleep	Device: CPAP - Flex; Use of Philips Respironics REMstar Auto A-Flex in C-Flex mode; Other Names: Philips Respironics REMstar Auto A-Flex

Outcome Measures

Primary Outcome Measures

1. Adherence to CPAP Pre-crossover [5 weeks after initiation of treatment]

   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).

2. Adherence to CPAP Overall Study [9 weeks after initiation of treatment]

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

Secondary Outcome Measures

1. CPAP Efficacy [5 weeks after initiation of treatment]

   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).

2. CPAP Efficacy [9 weeks after initiation of treatment]

   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.

Other Outcome Measures

1. Adherence to CPAP Overall Study, Subjects With High Nasal Resistance [9 weeks after initiation of treatment]

   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.

2. Adherence to CPAP Overall Study, Subjects With Low Nasal Resistance [9 weeks after initiation of treatment]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Environmental and Occupational Health Sciences Institute	Piscataway	New Jersey	United States	08854
2	New York University School of Medicine Clinical Center of Excellence	New York	New York	United States	10016
3	Mount Sinai School of Medicine	New York	New York	United States	10029

Sponsors and Collaborators

• Rutgers, The State University of New Jersey
• NYU Langone Health

Investigators

• Principal Investigator: Jag Sunderram, MD, Rutgers RWJMS
• Principal Investigator: Indu Ayappa, PhD, NYUMC

Study Documents (Full-Text)

• Study Protocol - May 18, 2016
• Statistical Analysis Plan - Jan 3, 2020

More Information

Publications

None provided.

• Responsible Party: Jag Sunderram, MD, Associate Professor, Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT01753999
• Other Study ID Numbers: 2012002164; 1U01OH010415-01
• First Posted: Dec 21, 2012
• Last Update Posted: Nov 4, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Jag Sunderram, MD, Associate Professor, Rutgers, The State University of New Jersey: World Trade Center (WTC); nasal symptoms; nasal inflammation; CPAP
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Study Results

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 Detail	Subjects without OSA were excluded from the trial.

Arm/Group Title	Standard CPAP Followed by CPAP-Flex	CPAP-Flex Followed by Standard CPAP
Arm/Group Description	Participants were first treated with standard CPAP (continuous positive airway pressure with constant pressure) using a REMstar Auto A-flex in standard CPAP therapy mode for 4 weeks. The therapy mode was then switched to CPAP-Flex for 4 weeks. CPAP-Flex provides a decrease in pressure during expiration.	Participants were treated with CPAP-Flex (continuous positive airway pressure with a decrease in pressure during expiration) using a REMstar Auto A-flex in C-Flex mode for 4 weeks. The therapy mode was then switched to standard CPAP for 4 weeks. Standard CPAP provides a constant pressure (no decrease after expiration).
Period Title: Period 1 - Initial Assignment
STARTED	155	162
Received Intervention	144	146
COMPLETED	116	112
NOT COMPLETED	39	50
Period Title: Period 1 - Initial Assignment
STARTED	116	112
Received Intervention	103	95
COMPLETED	99	89
NOT COMPLETED	17	23

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants who were randomized to receive either standard CPAP or CPAP-Flex.
Overall Participants	317
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	288 90.9%
>=65 years	29 9.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.29 (8.23)
Sex: Female, Male (Count of Participants)
Female	35 11%
Male	282 89%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	45 14.2%
Not Hispanic or Latino	264 83.3%
Unknown or Not Reported	8 2.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	12 3.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	32 10.1%
White	227 71.6%
More than one race	33 10.4%
Unknown or Not Reported	13 4.1%
Apnea and Hypopnea Index (AHI4%) (Events/hour) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Events/hour]	17.01 (14.42)
Total Nasal Resistance (Count of Participants)
High Nasal Resistance (LogTNR>0.8)	132 41.6%
Low Nasal Resistance (LogTNR<=0.8)	169 53.3%

Outcome Measures

1. Primary Outcome

Title	Adherence to CPAP Pre-crossover
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Standard CPAP	CPAP-Flex
Arm/Group Description	Use of a standard CPAP (continuous positive airway pressure) device with constant pressure for 4 weeks to improve breathing during sleep Standard CPAP: Use of the REMstar Auto A-Flex in standard CPAP therapy mode	Use of CPAP-Flex (continuous positive airway pressure) device with decreased pressure during expiration for 4 weeks to improve breathing during sleep CPAP - Flex: Use of Philips Respironics REMstar Auto A-Flex in C-Flex mode
Measure Participants	144	146
Median (Inter-Quartile Range) [Hours/night]	1	0.89

2. Primary Outcome

Title	Adherence to CPAP Overall Study
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard CPAP	CPAP-Flex
Arm/Group Description	Use of a standard CPAP (continuous positive airway pressure) device with constant pressure for 4 weeks to improve breathing during sleep Standard CPAP: Use of the REMstar Auto A-Flex in standard CPAP therapy mode	Use of CPAP-Flex (continuous positive airway pressure) device with decreased pressure during expiration for 4 weeks to improve breathing during sleep CPAP - Flex: Use of Philips Respironics REMstar Auto A-Flex in C-Flex mode
Measure Participants	239	249
Median (Inter-Quartile Range) [Hours/night]	1.03	0.8

3. Secondary Outcome

Title	CPAP Efficacy
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Standard CPAP	CPAP - Flex
Arm/Group Description	Use of a standard CPAP (continuous positive airway pressure) device with constant pressure for 4 weeks to improve breathing during sleep Standard CPAP: Use of the REMstar Auto A-Flex in standard CPAP therapy mode	Use of CPAP-Flex (continuous positive airway pressure) device with decreased pressure during expiration for 4 weeks to improve breathing during sleep CPAP - Flex: Use of Philips Respironics REMstar Auto A-Flex in C-Flex mode
Measure Participants	96	93
Mean (Standard Deviation) [Events/hour]	2.89 (3.06)	3.12 (2.95)

4. Secondary Outcome

Title	CPAP Efficacy
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Standard CPAP	CPAP-Flex
Arm/Group Description	Use of a standard CPAP (continuous positive airway pressure) device with constant pressure for 4 weeks to improve breathing during sleep Standard CPAP: Use of the REMstar Auto A-Flex in standard CPAP therapy mode	Use of CPAP-Flex (continuous positive airway pressure) device with decreased pressure during expiration for 4 weeks to improve breathing during sleep CPAP - Flex: Use of Philips Respironics REMstar Auto A-Flex in C-Flex mode
Measure Participants	157	147
Mean (Standard Deviation) [events/hour]	2.71 (2.76)	2.94 (2.65)

5. Other Pre-specified Outcome

Title	Adherence to CPAP Overall Study, Subjects With High Nasal Resistance
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Standard CPAP	CPAP-Flex
Arm/Group Description	Participants were first treated with standard CPAP (continuous positive airway pressure with constant pressure) using a REMstar Auto A-flex in standard CPAP therapy either in the first treatment period or in the second treatment period.	Participants were treated with CPAP-Flex (continuous positive airway pressure with a decrease in pressure during expiration) using a REMstar Auto A-flex in C-Flex either in the first treatment period or in the second treatment period.
Measure Participants	105	110
Mean (95% Confidence Interval) [Hours/night]	2.08	1.75

6. Other Pre-specified Outcome

Title	Adherence to CPAP Overall Study, Subjects With Low Nasal Resistance
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Standard CPAP	CPAP - Flex
Arm/Group Description	Participants were treated with standard CPAP (continuous positive airway pressure with constant pressure) using a REMstar Auto A-flex in standard CPAP therapy either in the first treatment period or in the second treatment period.	Participants were treated with CPAP-Flex (continuous airway pressure with a decrease in pressure during expiration) using a REMstar Auto A-flex in C-Flex either in the first treatment period or in the second treatment period.
Measure Participants	126	131
Mean (95% Confidence Interval) [Hours/night]	1.81	1.55

Adverse Events

Time Frame	Adverse event data were collected for 2 months after the start of the trial.
Arm/Group Title	Standard CPAP		CPAP - Flex
Arm/Group Description	Use of a standard CPAP (continuous positive airway pressure) device with constant pressure for 4 weeks to improve breathing during sleep Standard CPAP: Use of the REMstar Auto A-Flex in standard CPAP therapy mode		Use of CPAP-Flex (continuous positive airway pressure) device with decreased pressure during expiration for 4 weeks to improve breathing during sleep CPAP - Flex: Use of Philips Respironics REMstar Auto A-Flex in C-Flex mode
All Cause Mortality
	Standard CPAP		CPAP - Flex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/267 (0%)		0/278 (0%)
Serious Adverse Events
	Standard CPAP		CPAP - Flex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/267 (0%)		0/278 (0%)
Other (Not Including Serious) Adverse Events
	Standard CPAP		CPAP - Flex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/267 (0%)		0/278 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.