Positive Airway Pressure Therapy for Overlap Syndrome

Recruiting at 1 trial location

Overseen By Ruchi Rastogi, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Sedatives, Stimulants

Disqualifiers: Neuromuscular diseases, PTSD, Narcolepsy, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

250 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants have a stable treatment regimen for COPD, so you should not stop your current COPD medications. However, if you are taking medicines that cause or alter sleepiness, like sedative hypnotics or stimulants, you may need to stop those as they are excluded from the trial.

What data supports the effectiveness of Positive Airway Pressure Therapy for Overlap Syndrome?

Recent studies show that using continuous positive airway pressure (CPAP) in patients with overlap syndrome, which is a combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), can improve survival and reduce hospital visits. This suggests that CPAP is effective in managing the symptoms of overlap syndrome. ^{1 2 3 4 5}

Is Positive Airway Pressure Therapy safe for humans?

Positive Airway Pressure Therapy, including CPAP and BiPAP, is generally considered safe for humans. However, rare complications like pneumocephalus (air trapped in the skull) have been reported, especially after certain surgeries, so caution is advised in such cases. ^{1 6 7 8 9}

How does positive airway pressure treatment differ from other treatments for overlap syndrome?

Positive airway pressure (PAP) therapy, including CPAP and BiPAP, is unique for overlap syndrome because it directly addresses both obstructive sleep apnea and chronic obstructive pulmonary disease by maintaining open airways and improving breathing during sleep. Unlike other treatments that may focus on just one component of the syndrome, PAP therapy can reduce hospitalizations and improve survival by treating both conditions simultaneously. ^{1 2 3 4 10}

What is the purpose of this trial?

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.

Research Team

Susmita Chowdhuri, MD

Principal Investigator

John D. Dingell VA Medical Center, Detroit, MI

Eligibility Criteria

This trial is for veterans aged 60 or older with moderate-to-severe obstructive sleep apnea and chronic obstructive pulmonary disease, who have a significant history of smoking. They must not have used positive airway pressure before, be on stable COPD treatment, and not suffer from severe conditions that could affect cognitive function or safety.

Inclusion Criteria

My COPD treatment has not changed recently.

I am 60 years old or older.

I have severe sleep apnea and COPD, and I've smoked significantly in the past.

Exclusion Criteria

Pregnant women due to unknown risks

I am not taking medications that could affect my sleepiness.

I am currently experiencing severe depression or have unstable mental health.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PAP therapy or conservative care to study its effects on sleep quality, neurocognitive function, and quality of life

6 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Conservative care
• Positive airway pressure

Trial Overview The study tests if using positive airway pressure therapy can improve life quality, sleep quality, and neurocognitive function in older veterans with Overlap Syndrome (both OSA and COPD). Participants will either receive standard care or the addition of this therapy.

Participant Groups

Group I: Conservative care (control arm) Experimental Treatment 1 Intervention

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.

Group II: PAP therapy arm Active Control 1 Intervention

PAP Therapy will be provided to eligible patients with OVS. This is the active therapy arm.

Positive airway pressure is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Central Sleep Apnea (CSA)
• Mixed Sleep Apnea

Approved in European Union as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Central Sleep Apnea (CSA)
• Mixed Sleep Apnea

Approved in Canada as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Central Sleep Apnea (CSA)
• Mixed Sleep Apnea

Approved in Japan as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Central Sleep Apnea (CSA)
• Mixed Sleep Apnea

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a study of 32 hypercapnic overlap syndrome patients with moderate-to-severe obstructive sleep apnea, auto-trilevel positive airway pressure (PAP) therapy was found to be more effective than conventional Bilevel PAP therapy in reducing apnea events and carbon dioxide retention, leading to improved sleep quality.

Auto-trilevel PAP therapy resulted in lower arousal indices and daytime sleepiness, while also achieving higher minimum oxygen saturation levels during sleep, indicating it may be a better treatment option for patients who do not respond well to standard Bilevel PAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auto-trilevel versus bilevel positive airway pressure ventilation for hypercapnic overlap syndrome patients. Su, M., Huai, D., Cao, J., et al.[2019]

Overlap syndrome, which involves both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), leads to more severe health issues such as increased hypoxemia, hypercapnea, pulmonary hypertension, and right heart failure compared to COPD alone.

It is crucial to actively screen for overlap syndrome in COPD patients and treat it with continuous positive airway pressure (CPAP) alongside oxygen therapy and appropriate COPD medications to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The overlap syndrome: obstructive sleep apnea and chronic obstructive pulmonary disease]. Shteinberg, M., Weiler-Ravel, D., Adir, Y.[2009]

In a study of 319 elderly patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) who started positive airway pressure (PAP) therapy, hospitalization rates for COPD-related conditions significantly decreased from 25.4% to 19.4% in the year following treatment.

While PAP therapy did not significantly reduce overall emergency room visits or all-cause hospitalizations, it was particularly beneficial for older adults and those with more complex COPD and multiple comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of PAP therapy on hospitalization rates in Medicare beneficiaries with COPD and coexisting OSA. Singh, G., Agarwal, A., Zhang, W., et al.[2021]

The overlap syndrome, which involves both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), has shown improved patient outcomes when treated with continuous positive airway pressure (CPAP), including better survival rates and fewer exacerbations.

It is recommended that physicians screen COPD patients for OSA and consider starting CPAP treatment promptly for those diagnosed with OSA, as this could enhance their overall health management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of chronic obstructive pulmonary disease and the overlap syndrome. Kouns, A., Phillips, B.[2021]

In a study of 21 patients with overlap syndrome and hypercapnia, Auto-trilevel PAP ventilation significantly reduced the number of apnea-hypopnea events and improved sleep quality compared to fixed BiPAP ventilation.

Auto-trilevel PAP also effectively lowered morning carbon dioxide levels and daytime sleepiness, demonstrating its superiority in managing hypercapnic overlap syndrome and enhancing overall patient comfort during sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of auto-trilevel positive airway ventilation in hypercapnic patients with overlap syndrome]. Quan, W., Ding, N., Dong, Y., et al.[2018]

A case report highlights a rare but serious complication of using BiPAP after surgery for a brain tumor, where the patient developed severe pneumocephalus, leading to an unplanned ICU admission.

The authors recommend caution when using CPAP or BiPAP in postoperative patients, especially those who have undergone head and neck procedures, due to potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumocephalus with BiPAP use after transsphenoidal surgery. Kopelovich, JC., de la Garza, GO., Greenlee, JD., et al.[2022]

In a study of 35 patients with moderate to severe obstructive sleep apnea (OSA), both Continuous Positive Airway Pressure (CPAP) and Auto Bi-level Pressure Relief-Positive Airway Pressure (ABPR-PAP) significantly reduced the apnea-hypopnea index (AHI), indicating effective treatment.

After 3 months, ABPR-PAP showed a comparable reduction in AHI to CPAP, with no significant differences in compliance or adverse events, suggesting that ABPR-PAP could be a comfortable alternative for patients who struggle with traditional CPAP therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auto bi-level pressure relief-PAP is as effective as CPAP in OSA patients--a pilot study. Blau, A., Minx, M., Peter, JG., et al.[2021]

Long-term nonadherence to CPAP therapy in patients with obstructive sleep apnea is linked to factors such as using CPAP for less than 4 hours per night, having moderate to severe sleep apnea, low self-efficacy, and lack of support from a bed partner.

The American Academy of Sleep Medicine recommends follow-up within the first two weeks of CPAP use to enhance adherence, emphasizing the need for an integrated approach that includes behavioral therapy and management of side effects, while pharmacologic options like sedative-hypnotics are less favored due to potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea. Shaukat, R., Gamal, Y., Ali, A., et al.[2022]

In a study of 28 patients who struggled with CPAP compliance due to pressure intolerance, both a new CPAP and a Bi-level PAP device improved usage significantly, with Bi-level PAP showing a trend towards better compliance (2.73 hours vs. 2.23 hours for new CPAP).

Despite the improvements in compliance, the overall effectiveness of Bi-level PAP for this group was not significantly better than new CPAP, although some patients with exhalation difficulties did show favorable trends with the Bi-level PAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of changing people with sleep apnea using CPAP less than 4 h per night to a Bi-level device. Gulati, A., Oscroft, N., Chadwick, R., et al.[2015]

In a study of 54 patients with sleep apnoea/hypopnoea syndrome, the average nightly usage of CPAP therapy was only 4.7 hours, which is less than the recommended duration for effective treatment.

There was no correlation between the severity of sleep apnoea and the amount of CPAP used, and patients who experienced side effects from the therapy tended to use it significantly less, highlighting the importance of monitoring and addressing side effects to improve compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compliance with CPAP therapy in patients with the sleep apnoea/hypopnoea syndrome. Engleman, HM., Martin, SE., Douglas, NJ.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Auto-trilevel versus bilevel positive airway pressure ventilation for hypercapnic overlap syndrome patients. [2019]

2. Israel pubmed.ncbi.nlm.nih.gov

[The overlap syndrome: obstructive sleep apnea and chronic obstructive pulmonary disease]. [2009]

3. Germany pubmed.ncbi.nlm.nih.gov

Impact of PAP therapy on hospitalization rates in Medicare beneficiaries with COPD and coexisting OSA. [2021]

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

New developments in the management of chronic obstructive pulmonary disease and the overlap syndrome. [2021]

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy of auto-trilevel positive airway ventilation in hypercapnic patients with overlap syndrome]. [2018]

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

Pneumocephalus with BiPAP use after transsphenoidal surgery. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Auto bi-level pressure relief-PAP is as effective as CPAP in OSA patients--a pilot study. [2021]

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

Adherence to Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea. [2022]

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

The impact of changing people with sleep apnea using CPAP less than 4 h per night to a Bi-level device. [2015]

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

Compliance with CPAP therapy in patients with the sleep apnoea/hypopnoea syndrome. [2019]