Hypercapnia Treatment for Sleep Apnea

(RECOV2SCI Trial)

Overseen By Abdulghani Sankari, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Mechanical ventilation, Heart failure, Stroke, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for sleep apnea, specifically targeting individuals with chronic spinal cord injuries. Researchers are testing whether daily hypercapnia treatments, involving controlled exposure to higher carbon dioxide levels, can improve breathing and sleep quality. Participants will receive either the hypercapnia treatment or a sham (placebo-like) treatment for two weeks. Ideal candidates include veterans with long-term spinal cord injuries who experience sleep-disordered breathing, as well as able-bodied individuals with obstructive sleep apnea. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance sleep quality for many.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that hypercapnia treatment, which involves carefully controlled exposure to higher levels of carbon dioxide, is generally well-tolerated. Although specific safety data for this study is not yet available, researchers are exploring hypercapnia as a potential treatment for sleep apnea and breathing problems. Other studies have shown that hypercapnia treatments can improve breathing issues without serious side effects. No major safety concerns have emerged so far, suggesting that this treatment could be safe. However, discussing participation with a doctor is important to ensure it aligns with individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for sleep apnea, which typically involve continuous positive airway pressure (CPAP) therapy or lifestyle changes, hypercapnia treatment offers a novel approach. This method leverages intermittent exposure to elevated carbon dioxide levels, which may enhance the body’s natural respiratory drive, potentially improving breathing patterns during sleep. Researchers are excited because this could provide a non-invasive alternative that trains the body to manage apnea episodes more effectively, possibly reducing dependence on devices like CPAP machines. This fresh angle on treatment could open up new possibilities for patients seeking less intrusive solutions.

What evidence suggests that hypercapnia treatment might be an effective treatment for sleep apnea in spinal cord injury?

Research has shown that treatments involving higher levels of carbon dioxide, known as hypercapnia, might improve breathing and reduce sleep apnea symptoms. In this trial, participants will receive intermittent hypercapnia treatment five days per week for two weeks. Studies have found that combining hypercapnia with periods of low oxygen, called intermittent hypoxia, can help stabilize breathing patterns. Another study discovered that this method can reduce the pressure needed to treat sleep apnea. While more research is needed, these findings suggest that hypercapnia treatment could be a promising option for people with sleep apnea, especially those with spinal cord injuries. ^{1 2 3 4 6}

Who Is on the Research Team?

Abdulghani Sankari, MD PhD

Principal Investigator

John D. Dingell VA Medical Center, Detroit, MI

Are You a Good Fit for This Trial?

This trial is for adults with chronic spinal cord injury (SCI) who have been injured for over 6 months and are experiencing sleep-disordered breathing. They must be able to consent to the study themselves and not be too ill to participate. People with severe heart failure, recent substance abuse, or certain health events affecting sleep cannot join.

Inclusion Criteria

I have sleep apnea but no spinal cord injury or disorder.

I have had a spinal cord injury for more than 6 months and have some level of impairment.

Exclusion Criteria

My heart's pumping ability is severely reduced.

I've had a recent health event like a stroke or surgery that could affect my sleep.

Alcohol or substance abuse (<90 days sobriety)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent hypercapnia treatment five days per week for two weeks

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hypercapnia treatment
• Sham treatment

Trial Overview The trial is testing a new treatment approach for sleep apnea in patients with spinal cord injuries by using daily hypercapnia treatments over two weeks. The effectiveness of this treatment will be compared against a sham (fake) treatment.

How Is the Trial Designed?

Group I: SCD Experimental Treatment 1 Intervention

Intermittent hypercapnia treatment five days per week for two weeks.

Group II: Able-Bodoed Experimental Treatment 1 Intervention

Intermittent hypercapnia treatment five days per week for two weeks.

Group III: Intervention hypercapnia arm Active Control 1 Intervention

Intermittent hypercapnia treatment five days per week for two weeks.

Hypercapnia treatment is already approved in United States for the following indications:

Approved in United States as Hypercapnia treatment for:

• Sleep apnea in spinal cord injury
• Respiratory recovery after spinal cord injury

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

VA Detroit Healthcare System

Collaborator

Trials

1

Recruited

30+

Detroit VA

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study of 24 morbidly obese subjects with sleep apnea, 50% exhibited hypercapnia, indicating elevated carbon dioxide levels in the blood, which suggests a significant prevalence of this condition in this population.

The research highlights that ventilatory restriction is a key factor contributing to diurnal alveolar hypoventilation in these individuals, as hypercapnic subjects had significantly lower lung capacities compared to those with normal carbon dioxide levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mechanisms of diurnal hypercapnia in sleep apnea syndromes associated with morbid obesity]. Laaban, JP., Orvoen-Frija, E., Cassuto, D., et al.[2016]

In a study of 13 obese patients with sleep apnea, those with chronic hypercapnia showed reduced ventilatory responses to increased carbon dioxide and low oxygen levels, indicating a link between hypercapnia and impaired respiratory control.

Despite the presence of hypercapnia, there was no clear relationship between the severity of sleep apnea and the type or frequency of apneas, suggesting that other factors may influence apnea patterns in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of ventilation in the obstructive sleep apnea syndrome. Garay, SM., Rapoport, D., Sorkin, B., et al.[2016]

Acute hypercapnia in patients with obstructive sleep apnea (OSA) is linked to reduced ventilation during breathing events, which can lead to chronic hypercapnia when awake.

The study suggests that the shift from acute to chronic hypercapnia involves a complex interaction between how the body controls breathing and how the kidneys manage bicarbonate levels, indicating potential targets for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential mechanism for transition between acute hypercapnia during sleep to chronic hypercapnia during wakefulness in obstructive sleep apnea. Berger, KI., Norman, RG., Ayappa, I., et al.[2021]

For patients with obstructive sleep apnea who struggle with positive pressure therapy, alternative treatments such as weight loss, sleep hygiene, positional therapy, and oxygen therapy can be effective options.

Pharmacological treatments can improve sleep-disordered breathing by enhancing ventilatory drive, increasing upper airway muscle tone, reducing REM sleep, and promoting wakefulness, although some methods are still experimental.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical treatment of obstructive sleep apnea. Qureshi, A., Lee-Chiong, TL.[2013]

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 of 75 morbidly obese patients with obstructive sleep apnea, adherence to positive airway pressure therapy significantly reduced daytime hypercapnia (PaCO2) and improved oxygen levels (PaO2), with the most benefits seen after 5 to 7 hours of daily use.

Patients who used the therapy for more than 4.5 hours daily showed a marked decrease in the need for daytime home oxygen therapy, dropping from 30% to 6%, highlighting the therapy's effectiveness in managing respiratory complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of adherence with positive airway pressure therapy on hypercapnia in obstructive sleep apnea. Mokhlesi, B., Tulaimat, A., Evans, AT., et al.[2018]

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 104 participants with mild to moderate obstructive sleep apnea, the use of sham-CPAP showed statistically significant but small changes in sleep quality, indicating it can serve as an effective placebo in clinical trials.

The differences observed in sleep metrics, such as decreased sleep efficiency and increased arousal, suggest that while sham-CPAP impacts sleep, these effects are minimal and clinically insignificant, supporting its use in evaluating true CPAP treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of sham-CPAP as a placebo in CPAP intervention studies. Rodway, GW., Weaver, TE., Mancini, C., et al.[2022]

In a randomized trial involving 48 patients with moderate to severe sleep apnea, those treated with optimal CPAP showed significantly greater improvements in sleepiness and other SAHS-related symptoms compared to those receiving sham CPAP, confirming the efficacy of CPAP treatment.

The study demonstrated that even patients who initially received sham CPAP experienced significant improvements in symptoms when switched to optimal CPAP, highlighting the treatment's effectiveness in enhancing overall health and productivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of CPAP treatment in daytime function in sleep apnea syndrome: a randomized controlled study with an optimized placebo. Montserrat, JM., Ferrer, M., Hernandez, L., et al.[2022]

Intermittent hypercapnia can lead to long-term depression of respiration and may prevent the beneficial effects of long-term facilitation when combined with intermittent hypoxia, suggesting a complex interaction between these conditions.

Sustained hypercapnia, especially when paired with intermittent hypoxia, may improve breathing stability during sleep and could help address issues related to sleep apnea, highlighting its potential therapeutic relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of intermittent or sustained carbon dioxide on intermittent hypoxia initiated respiratory plasticity. What is the effect of these combined stimuli on apnea severity? Mateika, JH., Panza, G., Alex, R., et al.[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 review of 15 studies involving 4,250 obese patients with obstructive sleep apnea (OSA), daytime hypercapnia was found in 19% of patients, and was significantly associated with higher body mass index (BMI) and apnea-hypopnea index (AHI), indicating more severe OSA.

Patients with daytime hypercapnia also exhibited lower lung function, as shown by reduced percent predicted values for FEV1, vital capacity, and total lung capacity, highlighting the importance of monitoring these factors for early intervention and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of hypercapnia in obese patients with obstructive sleep apnea: a systematic review and metaanalysis of cohort studies. Kaw, R., Hernandez, AV., Walker, E., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05536076?term=AREA%5BBasicSearch%5D(%22spinal%20cord%20injury%22)%20AND%20AREA%5BStdAge%5D(ADULT)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=8

Effect of Hypercapnia Treatment on Respiratory Recovery ... The investigators hypothesized that daily hypercapnia treatments improve respiratory symptoms and alleviate sleep apnea in patients with chronic spinal cord ...

2. trialx.com trialx.com/clinical-trials/listings/280838/effect-of-hypercapnia-treatment-on-respiratory-recovery-after-spinal-cord-injury/

Effect of Hypercapnia Treatment on Respiratory Recovery ... The investigators hypothesized that daily hypercapnia treatments improve respiratory symptoms and alleviate sleep apnea in patients with chronic ...

3. withpower.com withpower.com/trial/phase-scid-11-2022-84058

Hypercapnia Treatment for Sleep Apnea (RECOV2SCI Trial) Studies indicate that combining intermittent hypercapnia with intermittent hypoxia (low oxygen levels) could help stabilize breathing and reduce sleep apnea ...

4. journals.physiology.org journals.physiology.org/doi/full/10.1152/japplphysiol.00204.2017?doi=10.1152/japplphysiol.00204.2017

Exposure to intermittent hypoxia and sustained ... Our new finding is that exposure to mild intermittent hypoxia reduced the therapeutic pressure required to treat sleep apnea. These findings are consistent ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28684586/

Exposure to intermittent hypoxia and sustained ... NEW & NOTEWORTHY Our new finding is that exposure to mild intermittent hypoxia reduced the therapeutic pressure required to treat sleep apnea.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666459325000393

Hypercapnia as a preventative therapeutic strategy Studies have shown that hypocapnia can lead to reduced oxygen delivery to the brain, increased neuronal excitability, and neurotoxicity and ultimately posing ...