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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for obstructive sleep apnea (OSA), a condition where breathing stops and starts during sleep. The study tests whether delivering small amounts of carbon dioxide (CO2) during sleep can prevent these interruptions, especially in those with drive-dependent OSA. Participants will receive either real or sham (fake) CO2 treatment while sleeping to assess its effectiveness. This trial is suitable for individuals diagnosed with or suspecting OSA, particularly if they experience frequent daytime sleepiness or snoring. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could lead to new treatment options for OSA.

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.

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

Research has shown that using carbon dioxide (CO2) in sleep therapy may help treat sleep apnea. In one study with 26 individuals newly diagnosed with obstructive sleep apnea (OSA), a method called isocapnic rebreathing, which involves carefully controlled CO2 delivery, significantly reduced the number of breathing interruptions during sleep, as measured by the apnea-hypopnea index.

Another study found that a small amount of CO2 could stop central sleep apnea events, leading to better sleep quality. These results suggest that CO2 treatments can be effective and are generally well-tolerated for managing sleep apnea symptoms.

While CO2 therapy has shown positive results, side effects and individual reactions can differ. However, current evidence is promising, indicating that CO2 could be a safe option for treating sleep apnea. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Dynamic CO2 for obstructive sleep apnea because it introduces a unique approach to managing the condition. Unlike traditional treatments like CPAP machines, which use continuous airflow to keep airways open, Dynamic CO2 works by delivering short bursts of carbon dioxide just before respiratory events during sleep. This method aims to naturally stimulate the body's breathing drive, potentially reducing sleep disruptions without the need for constant positive airway pressure. By enhancing the body's natural responses, this technique could offer a more comfortable and less intrusive option for sleep apnea sufferers.

What evidence suggests that this trial's treatments could be effective for obstructive sleep apnea?

Research has shown that Dynamic CO2, one of the treatments studied in this trial, can help reduce breathing problems in people with sleep apnea. One study found that administering CO2 at specific times during sleep reduced breathing fluctuations by over 95%. Another study with sleep apnea patients demonstrated that isocapnic rebreathing significantly lowered the number of breathing disruptions. Additionally, low-dose CO2 therapy improved sleep quality by stopping central sleep apnea events. These findings suggest that Dynamic CO2 could be a promising treatment for obstructive sleep apnea, especially for those whose condition depends on their breathing drive. Participants in this trial will receive either Dynamic CO2 or Sham CO2 to evaluate their effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Scott Sands, PhD

Principal Investigator

Brigham and Women's Hospital and Harvard Medical School

Dillon Gilbertson

Principal Investigator

Brigham and Women's Hospital and Harvard Medical School

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01041924

Dynamic Carbon Dioxide (CO2) Administration for Sleep ...

An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2755997/

Dynamic CO2 therapy in periodic breathing: a modeling study ...

We found an optimal time window within the ventilation cycle (covering ∼1/6 of the cycle) during which CO2 delivery reduces ventilatory fluctuations by >95%.

3.

withpower.com

withpower.com/trial/phase-obstructive-sleep-apnea-osa-10-2023-1e920

Dynamic CO2 for Obstructive Sleep Apnea

In a study of 26 newly diagnosed obstructive sleep apnea (OSA) patients, treatment with isocapnic rebreathing significantly reduced the apnea-hypopnea index ( ...

4.

journals.physiology.org

journals.physiology.org/doi/10.1152/japplphysiol.00312.2023

Central sleep apnea treated by a constant low-dose CO2 ...

The study also shows that this therapy can eliminate central sleep apnea events with associated improvement of sleep quality. Several polysomnographic indices ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4506311/

Future of Sleep-Disordered Breathing Therapy Using a ...

CPAP is the treatment of choice, especially for OSA. ... Although CPAP therapy can be transformative for many patients, tolerance and adherence to CPAP have been ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01041924?term=Carbon%20Dioxide&rank=8

Dynamic Carbon Dioxide (CO2) Administration for Sleep ...

A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes.