Dynamic CO2 for Obstructive Sleep Apnea

Overseen By Atqiya Aishah, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Must not be taking: Opioids, Barbiturates

Disqualifiers: Unstable conditions, Heart failure, Insomnia, others

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

Compensation: Varies

Number of Visits: 4

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using CPAP or other sleep apnea treatments for 3 days before each study visit. If you are taking medications that depress breathing, like opioids or barbiturates, you cannot participate in the trial.

What data supports the effectiveness of the treatment Dynamic CO2 for Obstructive Sleep Apnea?

Research shows that adding carbon dioxide (CO2) can help stabilize breathing in sleep disorders, including sleep apnea, by preventing pauses in breathing. In one study, CO2 therapy helped a patient with severe sleep apnea maintain normal oxygen levels throughout the night, suggesting it could be a useful treatment for similar conditions. ^{1 2 3 4 5}

Is Dynamic CO2 therapy safe for humans?

Research indicates that CO2 therapy, used in various forms for sleep-related breathing disorders, has been tested in humans and shown to improve sleep quality without significant adverse effects. However, more studies are needed to fully understand its safety profile, especially in patients with heart conditions. ^{2 3 6 7 8}

How does the Dynamic CO2 treatment for obstructive sleep apnea differ from other treatments?

Dynamic CO2 treatment is unique because it involves inhaling low concentrations of carbon dioxide to stabilize breathing during sleep, which can help prevent apneas (pauses in breathing) by maintaining CO2 levels above the threshold that triggers them. This approach is different from standard treatments like CPAP (continuous positive airway pressure) that primarily focus on keeping the airway open. ^{1 2 3 4 6}

What is the purpose of this trial?

Obstructive sleep apnea (OSA) is a highly prevalent disorder that has major consequences for cardiovascular health, neurocognitive function, risk of traffic accidents, daytime sleepiness, and quality of life. For years, a "classic" model of OSA has been used to describe the disorder, which fails to capture it's complexity. Recently, a model for OSA called drive-dependent OSA was discovered be more prevalent in the OSA population. The drive-dependent subgroup benefits exclusively from increased ventilation, increased dilator muscle activity, and reduced event risk when drive spontaneously rises. This study seeks to provide direct evidence that reducing the loss of drive prevents the loss of ventilation, pharyngeal muscle activity, and thus the onset of OSA respiratory events, specifically in "drive-dependent" but not "classic" OSA. This will be achieved using CO2 delivered at precise times during breaths in sleep to prevent loss of overall ventilatory drive.

Research Team

Dillon Gilbertson

Principal Investigator

Brigham and Women's Hospital and Harvard Medical School

Scott Sands, PhD

Principal Investigator

Brigham and Women's Hospital and Harvard Medical School

Eligibility Criteria

This trial is for adults with diagnosed or suspected obstructive sleep apnea (OSA) who are not currently experiencing unstable medical conditions. Participants should be using CPAP or similar treatments but can withhold them for 3 days before study visits. Those with a highly-sensitive gag reflex, severe claustrophobia, recent cardiovascular events, on certain medications like opioids, or pregnant/nursing women cannot join.

Inclusion Criteria

I use CPAP or similar for sleep but can stop it for 3 days before study visits, unless my job involves driving or operating heavy machinery.

I have been diagnosed with severe sleep apnea or show symptoms of it.

Exclusion Criteria

You are allergic to lidocaine, which is used for intramuscular electrodes and catheter.

Pregnancy or nursing

You have trouble falling asleep or staying asleep (insomnia).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (virtual)

Baseline Sleep Study

Participants attend a baseline routine sleep study to confirm eligibility and establish baseline characteristics

1 night

1 visit (in-person)

Overnight Physiology Study

Participants attend an overnight physiology study with gold standard instrumentation to establish OSA phenotype

1 night

1 visit (in-person)

Dynamic CO2 Study

An overnight physiological intervention study dedicated to mitigating ventilatory drive decline with carefully-timed inspired CO2 stimulation

1 night

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the intervention

2-4 weeks

Treatment Details

Interventions

• Dynamic CO2
• Sham CO2

Trial Overview The study tests whether precise CO2 delivery during sleep can prevent the onset of OSA respiratory events in patients with 'drive-dependent' OSA. It compares the effects of dynamic CO2 versus sham (fake) CO2 to see if increasing ventilatory drive helps maintain breathing and muscle activity in the throat.

Participant Groups

Group I: Dynamic CO2 within Drive-Dependent OSA Experimental Treatment 1 Intervention

During sleep, before \~30 distinct respiratory events, we will administer \~2% CO2 for \~3-4 breaths.

Group II: Dynamic CO2 within Classic OSA Active Control 1 Intervention

During sleep, before \~30 distinct respiratory events, we will administer \~2% CO2 for \~3-4 breaths.

Group III: Sham CO2 within Drive-Dependent OSA Placebo Group 1 Intervention

During sleep, Sham CO2 (air) will be administered for \~3-4 breaths before respiratory events.

Group IV: Sham CO2 within Classic OSA Placebo Group 1 Intervention

During sleep, Sham CO2 (air) will be administered for \~3-4 breaths before respiratory events.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

Treatment of hypocapnic central sleep apnea requires a multi-faceted approach due to the challenges posed by a hyperactive respiratory chemoreflex, with options including sedatives for better NREM sleep and CO2 stabilization techniques.

Innovative therapies like adaptive ventilation, enhanced expiratory rebreathing space (EERS), and oral appliances can effectively manage complex apnea by stabilizing respiratory control and reducing the need for positive pressure therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative approaches to treatment of Central Sleep Apnea. Thomas, RJ.[2021]

In a study of 28 patients with severe obstructive sleep apnea (OSA) and chronic airflow limitation (CAL), 14 exhibited persistent awake hypercapnia (high CO2 levels), while the other 14 maintained normal CO2 levels, indicating variability in CO2 retention among patients with similar conditions.

The hypercapnic group had significantly lower oxygen saturation levels during sleep and were heavier, had narrower upper airways, and reported higher alcohol intake, suggesting that these factors may contribute to the differences in CO2 retention despite similar apnea indices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea with severe chronic airflow limitation. Comparison of hypercapnic and eucapnic patients. Chan, CS., Grunstein, RR., Bye, PT., et al.[2016]

In a study involving six adult men with severe mixed sleep-disordered breathing, the addition of low concentrations of carbon dioxide (0.5% to 1%) to positive airway pressure therapy significantly reduced the respiratory disturbance index, indicating improved control of their condition.

The treatment was well-tolerated with no reported adverse effects, and it effectively normalized the residual respiratory disturbance index, demonstrating that carbon dioxide can be a safe and effective adjunct therapy for patients who do not respond adequately to standard positive airway pressure alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-concentration carbon dioxide is an effective adjunct to positive airway pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing. Thomas, RJ., Daly, RW., Weiss, JW.[2019]

A 63-year-old man with severe non-obstructive sleep apnoea was successfully treated with a 3% CO2 concentration, which completely suppressed his apnoeas and maintained normal oxygen saturation throughout the night.

The treatment suggests that for patients with non-obstructive sleep apnoea linked to low carbon dioxide levels (hypocapnia), administering CO2 could be a safe and effective alternative, especially if their respiratory control system is functioning properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effect of inhaled CO2 in a patient with non-obstructive sleep apnoea. Villiger, PM., Hess, CW., Reinhart, WH.[2019]

In a study of 26 newly diagnosed obstructive sleep apnea (OSA) patients, treatment with isocapnic rebreathing significantly reduced the apnea-hypopnea index (AHI) by 69% in responders, indicating that stabilizing respiratory motor output can effectively manage OSA in patients with high chemosensitivity.

The study found that patients who responded to treatment had a greater controller gain and smaller CO2 reserve, suggesting that these pathophysiological traits can predict treatment success, while hyperoxia showed limited effectiveness in reducing OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea. Xie, A., Teodorescu, M., Pegelow, DF., et al.[2021]

A novel CO2 delivery system using a special open mask was tested on 18 patients with central sleep apnea, showing significant improvements in apnea-hypopnea index (AHI) and arousal index after treatment, indicating enhanced sleep quality.

The study demonstrated that individually titrated CO2 supplementation can effectively reduce the severity of sleep disordered breathing, suggesting this device could be a valuable treatment option for patients with central sleep apnea, particularly those with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central sleep apnea treated by a constant low-dose CO2 supplied by a novel device. Luo, YM., Chen, YY., Liang, SF., et al.[2023]

In a study involving eight patients with congestive heart failure and central sleep apnea, the use of added dead space (DS) during sleep significantly reduced the number of apnea episodes from 29 to 1 per hour, indicating its effectiveness in stabilizing breathing patterns.

The addition of DS also improved overall sleep quality by increasing arterial oxygen saturation and reducing fluctuations in oxygen levels, without causing significant changes in cardiovascular function, such as heart rate or blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiorespiratory effects of added dead space in patients with heart failure and central sleep apnea. Khayat, RN., Xie, A., Patel, AK., et al.[2019]

In a study of 38 patients with obstructive sleep apnea (OSA) and chronic daytime hypercapnia, it was found that their respiratory responses to increased carbon dioxide levels were significantly lower compared to normocapnic patients, indicating a diminished chemosensitivity to CO2.

The study identified that factors such as mean oxygen saturation during sleep, lung function impairment (measured by FEV1), and body mass index (BMI) were strong predictors of daytime hypercapnia in OSA patients, explaining 72% of the variance in carbon dioxide levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Respiratory responses to CO2 stimulation in hypercapnic patients with obstructive sleep apnea syndrome]. Franczuk, M., Radwan, L., Pływaczewski, R., et al.[2016]

References

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

Alternative approaches to treatment of Central Sleep Apnea. [2021]

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

Obstructive sleep apnea with severe chronic airflow limitation. Comparison of hypercapnic and eucapnic patients. [2016]

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

Low-concentration carbon dioxide is an effective adjunct to positive airway pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Beneficial effect of inhaled CO2 in a patient with non-obstructive sleep apnoea. [2019]

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

Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea. [2021]

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

Central sleep apnea treated by a constant low-dose CO2 supplied by a novel device. [2023]

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

Cardiorespiratory effects of added dead space in patients with heart failure and central sleep apnea. [2019]

8. Poland pubmed.ncbi.nlm.nih.gov

[Respiratory responses to CO2 stimulation in hypercapnic patients with obstructive sleep apnea syndrome]. [2016]