Impact of Positive Airway Pressure Therapy on Clinical Outcomes in Older Veterans With Chronic Obstructive Pulmonary Disease and Comorbid Obstructive Sleep Apnea (Overlap Syndrome)

Obstructive sleep apnea (OSA) and Chronic Obstructive Pulmonary Disease (COPD) are highly prevalent chronic respiratory diseases in the Veteran population. OSA co-occurring with COPD, known as Overlap Syndrome (OVS), is a complex chronic medical condition associated with grave consequences. OVS is highly prevalent in Veterans. Veterans with OVS may be at increased risk for cognitive deficits, poor sleep quality as well as a reduced quality of life (QoL). The overall objective is to study the effects of positive airway pressure therapy on clinical outcomes in patients with OVS.

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Obstructive Sleep Apnea; Elderly; COPD; Sleepiness; Sleep Apnea Syndrome; Neurocognitive Function; Overlap Syndrome; Positive Airway Pressure
• Intervention / Treatment: Other: Conservative care (control arm); Device: Positive airway pressure

Detailed Description

There are no studies regarding the impact of PAP therapy on sleep disturbance, cognitive function and quality of life in patients with OVS. The investigators' rationale is that in patients with moderate-severe OVS, PAP therapy will effectively alleviate sleepiness, sleep disturbances and cognitive deficits, and, thereby, improve QoL. 'PAP' includes either continuous positive airway pressure (CPAP) or noninvasive positive airway pressure ventilation (NIPPV).

Objectives:

Specifically, the investigators will study the effectiveness of PAP therapy vs. conservative care in reducing daytime sleepiness and in improving sleep quality and QoL in older Veterans with OVS.

The investigators will also explore whether CPAP is non-inferior to noninvasive positive airway pressure ventilation (NIPPV) in reducing daytime sleepiness, sleep disturbances and neurocognitive dysfunction, and in improving QoL in older Veterans with OVS.

• Study Type: Interventional
• Enrollment (Estimated): 668
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ruchi Rastogi, MS; Phone Number: (313) 576-4464; Email: ruchi.rastogi@va.gov

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-1916
      • Recruiting
      • John D. Dingell VA Medical Center, Detroit, MI
      • Contact: Edi Levi, MD; Phone Number: (313) 576-4451; Email: edi.levi@va.gov
      • Contact: Ruchi Rastogi, MS; Phone Number: 313-576-4464; Email: ruchi.rastogi@va.gov
      • Principal Investigator: Susmita Chowdhuri, MD MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• OSA with moderate-to-severe disease, AHI 20 per hour by in-lab polysomnography with concomitant moderate-severe COPD based on pulmonary function tests (PFTS) and with past significant history (>10 pack-years) of smoking
• Male or female gender
• Age greater than or equal to 60 years
• Stable treatment regimen for COPD

Exclusion Criteria:

• Current or prior treatment with PAP or oral appliance
• Central sleep apnea defined as central apnea index >5 per hour and comprising 50% of AHI
• Known primary neuromuscular diseases

• Disorders that may impact cognitive function including:

  • neurodegenerative disorders
  • traumatic brain injury
• untreated PTSD and/or history of learning disability
• Medicines that may cause or alter sleepiness: sedative hypnotics, or stimulants as these may alter the results
• Patient is actively suicidal due to depression, unstable mental health condition
• Epworth sleepiness score >16 (severe sleepiness) or a near-miss or prior automobile accident due to sleepiness within the past 12 months
• Narcolepsy is the primary sleep disorder, with requirement of stimulant medications
• Employed as a commercial driver or operating heavy machinery
• On long-term oxygen therapy prior to start of study, more than 12 hr/day
• Patients is unable to use either a nasal or face mask (e.g., facial trauma, claustrophobia)
• Consumption of >3 alcoholic beverages per day or current use of some illicit drugs, as these may contribute to cognitive deficits
• Patients who cannot give informed consent
• Patients receiving hospice care
• Pregnant women due to unknown risks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Conservative care (control arm); Eligible OVS patients will receive conservative care/usual care with education about sleep apnea and sleep hygiene via handouts and video instructions. This is the control arm.	Other: Conservative care (control arm); Eligible OVS patients will receive conservative care/usual care with education about sleep apnea and sleep hygiene via handouts and video instructions. This is the control arm.
Active Comparator: PAP therapy arm; PAP Therapy will be provided to eligible patients with OVS. This is the active therapy arm.	Device: Positive airway pressure; Positive airway pressure therapy. OVS patients randomized to PAP therapy arm will be titrated to optimal PAP therapy per standard protocol and assigned to use PAP therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive function Trails A and Trails B	Trails A and Trails B test will be administered to evaluate attention and psychomotor function. This score is adjusted for age, race, gender, and years of education. Scored on a Standard scale of 100 +/- 15 for normal ranges, above 115 is above average, below 85 is considered below average.	Change from baseline at 3 and 6 months
Neurocognitive function PASAT	PASAT (Paced Auditory Serial Addition Test) will be administered to evaluate vigilance and executive function. The PASAT is recorded as the total number of correct responses (from 0-60), or the percent of correct responses out of 60 (from 0-100), where a higher value is a better outcome.	Change from baseline at 3 and 6 months
Neurocognitive function Stroop color-word interference	Stroop color-word interference test will be administered to evaluate executive function. This score is adjusted for age, and years of education. Scored on a Standard scale of 100 +/- 15 for normal ranges, above 115 is above average, below 85 is considered below average.	Change from baseline at 3 and 6 months
Neurocognitive function DIGIT	DIGIT test will be administered to evaluate short-term and working memory. This score is adjusted for age. Scored on a Standard scale of 100 +/- 15 for normal ranges, above 115 is above average, below 85 is considered below average.	Change from baseline at 3 and 6 months
Neurocognitive function WASI	Abbreviated Wechsler Abbreviated Scale of Intelligence (WASI) will be administered to evaluate verbal comprehension and working memory. This score is adjusted for age. Scored on a Standard scale of 100 +/- 15 for normal ranges, above 115 is above average, below 85 is considered below average.	Change from baseline at 3 and 6 months
Neurocognitive function WMS	Wechsler Memory test (WMS) will be administered to measure Verbal comprehension, and working and visual memory. Scored on a Standard scale of 100 +/- 15, where a higher score is a better outcome.	Change from baseline at 3 and 6 months
Neurocognitive function PVT	Psychomotor Vigilance Test (PVT) will be administered to measure Alertness and vigilance, in terms of number of lapses and reaction time. The performance score ranges from 0-100, where a higher value is a better outcome.	Change from baseline at 3 and 6 months
Neurocognitive function HVLT-R	Hopkins Verbal Learning Test - Revised (HVLT-R) will be administered to evaluate Verbal learning and memory. Scored on a Standard scale of 100 +/- 15, where a higher score is a better outcome.	Change from baseline at 3 and 6 months
Sleepiness ESS	Epworth sleepiness scale (ESS) score will be measured. This score is on a scale of 0-24, where a higher value indicates greater degree of sleepiness.	Change from baseline at 3 and 6 months
Sleep quality PSQI	Pittsburgh Sleep Quality Index (PSQI) is a detailed assessment of subject sleep quality over the most recent month by considering seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score to assess sleep quality on a scale of "poor" to "good".	Change from baseline at 3 and 6 months
Quality of life SF-36v2	QoL will be assessed using the survey SF-36v2 Health survey. Thirty-five of the SF-36v2 items are used to measure eight domains of health-related quality of life. These are on a scale of 0-100, where higher values indicate a better outcome.	Change from baseline at 3 and 6 months
Quality of life FOSQ	Disease specific QoL will be assessed using the Functional Outcomes of Sleep Questionnaire FOSQ/(FOSQ). There are 5 subscale domains of the FOSQ (General Productivity, Social Outcome, Activity Level, Vigilance, and Intimate Relationships and Sexual Activity). There all range from 0-20, where a higher value is a better outcome. The total FOSQ is the sum of these subscale domains and ranges from 0-100, where a higher value is a better outcome.	Change from baseline at 3 and 6 months
Quality of life SGRQ	Disease specific QoL will be assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ has three subscale domains (Symptoms, Activity, and Impacts), which range from 0-100, where a higher value indicates a worse outcome. The total SGRQ is the average of these subscale domains and is on a scale of 0-100, where a higher value is a worse outcome.	Change from baseline at 3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hours of nightly positive airway pressure (PAP) use	Collection of PAP adherence data from the smart card of the PAP machine or from online data.	Change from baseline at 3 and 6 months
Patient preferance for type of PAP (PAP arm)	A visual analog scale to determine preference to CPAP vs NIPPV therapy. A scores will range from -10 to +10, where a higher score is better.	at 3 and 6 months
Fatigue severity	Fatigue Severity Scale (FSS): FSS measures how fatigue affects motivation, exercise, physical functioning, carrying out duties, interfering with work, family, or social life. Where a higher value is a worse outcome.	Change from baseline at 3 and 6 months
Sleep-dependent memory	In a subgroup of patients, the investigators will perform Word-pair test and PVT before and after sleep period, this is an exploratory measure.	At baseline and at 3 months
Blood CO2 or bicarbonate level	Test is being done to evaluate for presence or absence of hypercapnia	At baseline and at 6 months

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Susmita Chowdhuri, MD MS, John D. Dingell VA Medical Center, Detroit, MI

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 25, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; quality of life; cognitive function; Nervous System Diseases; Sleep Apnea, Obstructive; Sleep Apnea Syndromes; Apnea; Respiration Disorders; sleepiness; positive airway pressure; Signs and Symptoms, Respiratory
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Lung Diseases; Lung Diseases, Obstructive; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Sleepiness; Pulmonary Disease, Chronic Obstructive; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Respiratory Tract Diseases; Nervous System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory
• Other Study ID Numbers: E3124-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No