Sleep Apnea Treatments for Sleep Apnea with COPD

Recruiting in Palo Alto (17 mi)

Overseen by Susmita Chowdhuri, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Trial Summary

What is the purpose of this trial?

Cognitive dysfunction in the aging Veteran population is a growing health concern in the Veterans Health System. It is not known whether OSA coexisting with COPD will enhance the risk for cognitive dysfunction. The investigators sought to investigate whether these two highly prevalent diseases, that often co-exist as the 'Overlap Syndrome', combine to enhance cognitive impairment in the elderly Veteran population. Thus, the investigators will study whether elderly patients with Overlap syndrome have increased cognitive deficits compared with OSA or COPD alone. Additionally, treatment of OSA with positive airway pressure (PAP) has been shown to improve neurocognitive function in moderate-to-severe OSA while cognitive decline in COPD may be reversible through treatment with long-term oxygen therapy. The investigators will also study whether treatment with positive airway pressure (PAP) and supplemental oxygen vs PAP alone will improve cognitive function and improve quality of life of elderly Veterans.

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.

What data supports the effectiveness of the treatment for Sleep Apnea with COPD?

Research shows that Positive Airway Pressure (PAP) therapy, which includes treatments like CPAP and BiPAP, is effective in reducing the severity of sleep apnea and improving quality of life. This suggests that similar treatments could be beneficial for patients with both sleep apnea and COPD. ^{1 2 3 4 5}

Is non-invasive positive pressure ventilation (NIPPV) safe for humans?

Non-invasive positive pressure ventilation (NIPPV) has been used in patients with chronic obstructive pulmonary disease (COPD) and respiratory failure, and while its long-term benefits are still debated, it is generally considered safe for human use. ^{6 7 8 9 10}

How is the treatment NIPPV and/or oxygen unique for sleep apnea with COPD?

NIPPV (Non-Invasive Positive Pressure Ventilation) is unique because it provides breathing support without the need for invasive procedures, making it suitable for home use. It is particularly beneficial for patients with both sleep apnea and COPD, as it helps manage breathing difficulties by maintaining airway pressure, especially during sleep. ^{7 9 10 11 12}

Research Team

Susmita Chowdhuri, MD

Principal Investigator

John D. Dingell VA Medical Center, Detroit, MI

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• NIPPV and /or oxygen (Device)
• Positive airway pressure (Device)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

Findings from Research

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]

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 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]

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 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]

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]

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 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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Advances in Treatment of Sleep-Disordered Breathing. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Adenotonsillotomy versus adenotonsillectomy in pediatric obstructive sleep apnea: A 5-year RCT. [2022]

3. England 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. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Positional therapy in sleep apnoea - one fits all? What determines success in positional therapy in sleep apnoea syndrome. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Proportional assist ventilation with load-adjustable gain factors in critically ill patients: comparison with pressure support. [2021]

6. India pubmed.ncbi.nlm.nih.gov

Early predictors of success of non-invasive positive pressure ventilation in hypercapnic respiratory failure. [2020]

7. England 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. [2022]

8. England 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Nocturnal non-invasive positive pressure ventilation for stable chronic obstructive pulmonary disease. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Nocturnal non-invasive positive pressure ventilation for stable chronic obstructive pulmonary disease. [2022]

11. United States 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. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Sleep-Related Breathing Disorders: When CPAP Is Not Enough. [2022]