Sleep Apnea Treatments for Sleep Apnea with COPD

Overseen By Ruchi Rastogi, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Hypnotics, Anxiolytics, Sedating antidepressants, others

Disqualifiers: Mild COPD, Mild OSA, Current smokers, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how treatments for sleep apnea (interrupted breathing during sleep) and COPD (a lung disease causing breathing difficulty) might affect memory and thinking skills in older veterans. Researchers aim to determine if having both conditions worsens cognitive problems compared to having just one. Participants will receive either positive airway pressure (PAP) treatment alone or PAP with extra oxygen (known as NIPPV and/or oxygen therapy) to identify which is more effective. Veterans aged 60 and older with both moderate-to-severe sleep apnea and COPD, who have a significant history of smoking, might be suitable for this study.

As an unphased trial, this study offers veterans the opportunity to contribute to important research that could enhance understanding and treatment of these conditions.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that affect alertness or daytime functioning, such as sedatives, stimulants, and some antidepressants. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that noninvasive positive pressure ventilation (NIPPV) is generally safe for people with COPD, a lung disease that makes breathing difficult. Studies indicate that NIPPV can improve breathing and may lead to better health outcomes. Those who use NIPPV at home often experience a better quality of life compared to those who do not.

Supplemental oxygen is a common treatment for COPD, providing extra oxygen often needed by people with this condition. Both NIPPV and oxygen therapy are well-tolerated by most patients. No reports of serious safety issues exist for these treatments in people with COPD and obstructive sleep apnea (OSA), a condition where breathing stops and starts during sleep.

In summary, both NIPPV and oxygen therapy are considered safe for people with COPD and OSA. They are widely used and have been shown to improve breathing and quality of life. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they combine non-invasive positive pressure ventilation (NIPPV) and oxygen therapy to target sleep apnea in individuals with COPD, a condition often managed with just continuous positive airway pressure (CPAP) or lifestyle changes. Unlike standard treatments that primarily focus on opening the airway during sleep, NIPPV offers the added benefit of improving ventilation and oxygenation, potentially reducing the burden on the respiratory system. This dual approach could enhance breathing efficiency and sleep quality, offering a promising alternative for patients struggling with both sleep apnea and COPD.

What evidence suggests that this trial's treatments could be effective for cognitive dysfunction in elderly Veterans with sleep apnea and COPD?

Research has shown that non-invasive breathing support and oxygen can benefit individuals with both COPD and sleep apnea. In this trial, participants will receive either non-invasive positive pressure ventilation (NIPPV) and/or oxygen or positive airway pressure (PAP) therapy. These treatments may enhance health and extend life for patients with these conditions. Specifically, PAP therapy can improve sleep and overall health for those with severe overlap syndrome. Some studies suggest that using this breathing support at home results in better health outcomes compared to not using any device. While more research is needed, current evidence supports the potential benefits of these treatments in improving quality of life and mental function for affected individuals. ^{1 2 4 6 7}

Who Is on the Research Team?

Susmita Chowdhuri, MD

Principal Investigator

John D. Dingell VA Medical Center, Detroit, MI

Are You a Good Fit for This Trial?

This trial is for elderly veterans aged 60 or older with moderate-to-severe obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). Participants must have a significant history of smoking but cannot be current smokers, not on oxygen or CPAP therapy, and without central sleep apnea, recent acute illness, psychiatric illnesses requiring sedation, unstable heart conditions, or life expectancy under six months.

Inclusion Criteria

I am either male or female.

I am 60 years old or older.

I have moderate-to-severe COPD, a history of significant smoking, and recent lung function tests.

Exclusion Criteria

Patients unable to use either a nasal or face mask (e.g., facial trauma)

I have been diagnosed with mild sleep apnea.

I am taking medication for a psychiatric condition that makes me sleepy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either PAP and/or supplemental oxygen or CPAP alone for 3 months to evaluate impact on neurocognitive function, sleepiness, and quality of life

12 weeks

Regular visits for monitoring and data collection

Follow-up

Participants are monitored for changes in neurocognitive function, sleepiness, and quality of life after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NIPPV and /or oxygen
• Positive airway pressure

Trial Overview The study aims to see if positive airway pressure (PAP) treatments alone or combined with supplemental oxygen can improve cognitive function and quality of life in elderly veterans with 'Overlap Syndrome'—a combination of OSA and COPD. The effectiveness will be compared between those receiving just PAP versus PAP plus additional oxygen.

How Is the Trial Designed?

Group I: Positive airway pressure therapy Active Control 2 Interventions

Control group patients will receive standard care with PAP- positive airway pressure.

Group II: COPD Active Control 1 Intervention

The COPD control group will be patients with moderate-to-severe COPD alone per the GOLD criteria.

Group III: OSA and comorbid COPD Active Control 1 Intervention

Eligible elderly (age \>/=60yrs) Veterans with moderate to severe Overlap Syndrome.

NIPPV and /or oxygen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as NIPPV and/or Oxygen for:

• Obstructive Sleep Apnea (OSA)
• Chronic Obstructive Pulmonary Disease (COPD)
• Overlap Syndrome

Approved in European Union as NIPPV and/or Oxygen for:

• Obstructive Sleep Apnea (OSA)
• Chronic Obstructive Pulmonary Disease (COPD)
• Respiratory Failure

Approved in Canada as NIPPV and/or Oxygen for:

• Obstructive Sleep Apnea (OSA)
• Chronic Obstructive Pulmonary Disease (COPD)
• Acute Respiratory Distress

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Positive airway pressure (PAP) therapy is the gold standard for treating sleep-disordered breathing, significantly reducing apnea-hypopnea index (AHI) and improving patient quality of life, but many patients struggle with adherence due to discomfort.

Emerging treatments like the hypoglossal nerve stimulator and phrenic nerve stimulator offer promising alternatives by directly stimulating nerves to alleviate airflow obstruction and stabilize breathing patterns, respectively, thus improving AHI severity and quality of life for patients with obstructive and central sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Treatment of Sleep-Disordered Breathing. Lou, BX., Greenberg, H., Korotun, M.[2021]

Nocturnal non-invasive positive pressure ventilation (NIPPV) did not show consistent significant effects on lung function, gas exchange, or exercise tolerance in stable hypercapnic patients with COPD, based on a review of randomized controlled trials.

While there was a modest improvement in the 6-minute walking distance (6MWD) of 27.5 meters, the wide confidence intervals indicate variability in patient responses, and the small sample sizes limit the ability to draw definitive conclusions about the efficacy of NIPPV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nocturnal non-invasive positive pressure ventilation for stable chronic obstructive pulmonary disease. Wijkstra, PJ., Lacasse, Y., Guyatt, GH., et al.[2018]

A systematic review of 13 studies involving 5465 patients found that using noninvasive positive pressure ventilation (NIPPV) after bariatric surgery does not increase the risk of anastomotic dehiscence, a serious complication.

NIPPV was associated with a reduced risk of respiratory complications in post-bariatric surgery patients, suggesting it is a safe and effective option for managing obstructive sleep apnea in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive positive pressure ventilation in the immediate post-bariatric surgery care of patients with obstructive sleep apnea: a systematic review. Tong, S., Gower, J., Morgan, A., et al.[2018]

In patients with hypercapnic COPD on long-term oxygen therapy, adding tele-assistance (TA) significantly reduced the risk of exacerbations, especially when combined with non-invasive ventilation (NIV).

TA also lowered the risk of hospitalizations when added to long-term oxygen therapy alone, indicating its potential as an effective support strategy in managing COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There Any Additional Effect of Tele-Assistance on Long-Term Care Programmes in Hypercapnic COPD Patients? A Retrospective Study. Vitacca, M., Paneroni, M., Grossetti, F., et al.[2018]

Bilevel positive airway pressure (BPAP) devices have been developed to effectively treat complex sleep-related breathing disorders that do not respond to traditional CPAP therapy, enhancing patient care for conditions like obstructive sleep apnea (OSA).

Advanced BPAP therapies, including adaptive servoventilation and volume-assured pressure support, provide tailored noninvasive ventilation options to address various hypoventilation disorders and central sleep apnea syndromes, showcasing their versatility in managing complex respiratory issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep-Related Breathing Disorders: When CPAP Is Not Enough. Selim, B., Ramar, K.[2022]

In a study of 11 patients with severe COPD and chronic hypercapnoeic respiratory failure, non-invasive nocturnal intermittent positive pressure ventilation (NIPPV) significantly improved arterial blood gas tensions over two years, despite ongoing deterioration in lung function.

NIPPV also halved hospital admissions and general practitioner consultations within the first year of treatment, suggesting it is a well-tolerated and effective management strategy for these patients, potentially leading to prolonged survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domiciliary nocturnal intermittent positive pressure ventilation in patients with respiratory failure due to severe COPD: long-term follow up and effect on survival. Jones, SE., Packham, S., Hebden, M., et al.[2022]

In a five-year follow-up study of 79 non-obese children with obstructive sleep apnea (OSA), both adenotonsillectomy (ATE) and intracapsular adenotonsillotomy (ATT) showed significant reductions in the severity of OSA, measured by the Obstructive Apnea/Hypopnea Index (OAHI), with no significant difference between the two procedures.

Despite the effectiveness of ATT, there is a risk of recurrence, as indicated by the need for some children in the ATT group to undergo ATE later, highlighting the importance of long-term follow-up for patients treated with ATT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenotonsillotomy versus adenotonsillectomy in pediatric obstructive sleep apnea: A 5-year RCT. Sjölander, I., Borgström, A., Nerfeldt, P., et al.[2022]

In a study of 66 COPD patients over two years, adding noninvasive intermittent positive pressure ventilation (NIPPV) to pulmonary rehabilitation significantly improved health-related quality of life (HRQoL) and several other health metrics, despite not showing a significant difference in the Chronic Respiratory Questionnaire scores.

The addition of NIPPV also led to improvements in mood, dyspnea, gas exchange, exercise tolerance, and lung function, indicating that NIPPV can enhance the overall treatment outcomes for patients with chronic hypercapnic respiratory failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: a randomized controlled trial. Duiverman, ML., Wempe, JB., Bladder, G., et al.[2022]

In a study of 208 critically ill patients, proportional assist ventilation with load-adjustable gain factors (PAV+) showed a significantly lower failure rate (11.1%) compared to pressure support ventilation (PS) (22.0%), indicating better effectiveness in supporting spontaneous breathing.

PAV+ also resulted in fewer instances of patient-ventilator dyssynchronies (5.6% vs. 29.0% in PS), suggesting it provides a more synchronized and comfortable breathing experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proportional assist ventilation with load-adjustable gain factors in critically ill patients: comparison with pressure support. Xirouchaki, N., Kondili, E., Vaporidi, K., et al.[2021]

A meta-analysis of seven studies involving 245 stable hypercapnic COPD patients found that nocturnal non-invasive positive pressure ventilation (NIPPV) did not show consistent significant improvements in key health measures such as gas exchange, exercise tolerance, or quality of life.

While the mean increase in six-minute walking distance (6MWD) was 27.7 meters, this change was not statistically significant, indicating that the true effect of NIPPV on exercise capacity remains uncertain, especially given the small sample sizes of the studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nocturnal non-invasive positive pressure ventilation for stable chronic obstructive pulmonary disease. Struik, FM., Lacasse, Y., Goldstein, R., et al.[2022]

In a study of 112 patients with supine-exclusive sleep apnoea syndrome, 75% achieved a significant reduction in their apnea-hypopnea index (AHI) to below 5 events per hour after using positional therapy, indicating its efficacy as a treatment option.

One year later, 32% of patients remained on positional therapy with sustained AHI <5/h, suggesting that with proper adherence, positional therapy can be a viable long-term solution for managing sleep apnoea, particularly influenced by body mass index (BMI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positional therapy in sleep apnoea - one fits all? What determines success in positional therapy in sleep apnoea syndrome. Troester, N., Palfner, M., Dominco, M., et al.[2018]

In a study of 100 patients with acute hypercapnic respiratory failure, 76% showed significant improvement in clinical parameters and arterial blood gas measurements after starting non-invasive positive pressure ventilation (NIPPV).

Improvement in heart rate, respiratory rate, pH, and PCO2 within the first hour of NIPPV treatment was a strong predictor of treatment success, while those who failed to respond often required intubation shortly after.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early predictors of success of non-invasive positive pressure ventilation in hypercapnic respiratory failure. Bhattacharyya, D., Prasad, B., Tampi, PS., et al.[2020]

Citations

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Prognostic efficacy of non-invasive ventilation in patients with ... NIV may improve outcomes and survival in patients with severe OS of comorbid COPD and OSA. Confirmatory studies are needed to prove benefits.

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Noninvasive Positive Pressure Ventilation (NIPPV) in the ... This final NCD provides coverage of RADs for the treatment of chronic respiratory failure that often accompanies COPD.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1087079225001212

Positive airway pressure therapies improve sleep ... PAP therapies include non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP), with the latter being used only for OHS, ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2760390

Association of Home Noninvasive Positive Pressure ... Home NIPPV, compared with no device use, was significantly associated with better clinical outcomes and no significant difference in quality of life.

5. atsjournals.org atsjournals.org/doi/10.1164/rccm.202109-2035OC

Impact of Positive Airway Pressure Therapy Adherence on ... This retrospective observational study investigated the effects of PAP on health outcomes, resource usage, and costs in patients with overlap syndrome.

6. journal.chestnet.org journal.chestnet.org/article/S0012-3692(24)00041-2/fulltext

Home Noninvasive Ventilation in COPD - CHEST Evidence is increasing that long-term noninvasive ventilation (LTNIV) can improve outcomes in individuals with severe, hypercapnic COPD.

7. aetna.com aetna.com/cpb/medical/data/400_499/0452.html

Positive Pressure Ventilation - Medical Clinical Policy ... Noninvasive positive pressure ventilation (NPPV) is considered medically necessary for postoperative hypoxemic respiratory failure that is refractory to or not ...