Electrical + Pharmacological Stimulation for Sleep Apnea

DG
DP
Overseen ByDaniel P Vena, PhD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining a medication called AtoOxy (a mix of atomoxetine and oxybutynin) with a device that stimulates a tongue muscle, known as unilateral hypoglossal nerve stimulation (HGNS), can improve breathing during sleep for people with obstructive sleep apnea (OSA). Participants will test various combinations of the device and medication to identify the most effective treatment. Those with OSA who already have or are acquiring the device and can manage without it for short periods might be suitable candidates. The goal is to reduce sleep disruptions and enhance breathing. As a Phase 1/Phase 2 trial, this research focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage development.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial excludes participants using SNRIs/SSRIs or anticholinergic medications during the study.

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

Research has shown that the combination of atomoxetine and oxybutynin (AtoOxy) is generally safe for treating obstructive sleep apnea (OSA). In one study, participants used this combination for 30 days, which reduced the severity of OSA without major safety issues. Most participants tolerated it well.

The hypoglossal nerve stimulation (HGNS) device is an approved treatment for OSA. Previous studies have demonstrated its effectiveness and safety. Patients using this device experienced significant improvements in sleep quality without major side effects.

Combining AtoOxy with HGNS aims to enhance treatment effectiveness. While researchers continue to study AtoOxy, current data suggest it is well-tolerated, especially for short-term use like in this trial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for sleep apnea because they introduce a novel combination approach. Traditional treatments like CPAP machines and oral appliances mainly focus on keeping airways open mechanically. However, HGNS (Hypoglossal Nerve Stimulation) directly stimulates the nerves that control tongue movement, helping to keep the airway open naturally, while AtoOxy (Atomoxetine combined with Oxybutynin) represents a new pharmacological strategy aimed at enhancing airway muscle tone and reducing apneic events. This dual approach could offer a more comprehensive solution by addressing the condition from both a neural and muscular standpoint, potentially improving outcomes for patients who do not respond well to current standard therapies.

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

Research has shown that stimulating the hypoglossal nerve (HGNS) effectively treats obstructive sleep apnea (OSA) by keeping airways open during sleep. This treatment can significantly improve sleep quality and reduce daytime tiredness for some individuals. Additionally, the combination of two medications, atomoxetine and oxybutynin (AtoOxy), has shown promise in enhancing throat muscle function, which can alleviate OSA symptoms. Some studies have found that this combination can reduce apnea events by more than 50% in certain patients. In this trial, participants will receive HGNS, AtoOxy, and the combination of HGNS with AtoOxy in different sequences. Using HGNS together with AtoOxy might offer even better results, especially for those who do not experience sufficient relief from HGNS alone. Early research suggests that this combined approach may further reduce the frequency of breathing interruptions during sleep.16789

Who Is on the Research Team?

SA

Scott A Sands, PhD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults with obstructive sleep apnea who already have a hypoglossal nerve stimulation (HGNS) device implanted. Participants should not have other major health issues that would interfere with the study.

Inclusion Criteria

I am between 18 and 79 years old.
Willingness to withhold HGNS while testing therapies (up to 6 weeks with HGNS off to assess benefits of HGNS therapy)
I have or am scheduled to get a hypoglossal nerve stimulation device implanted.
See 1 more

Exclusion Criteria

Any uncontrolled medical condition
Occupational driving (truck drivers, fork-lift operation, taxi/uber drivers)
History of traffic accidents attributable to sleepiness or fatigue (<2 years)
See 7 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a four-period randomized placebo-controlled cross-over trial assessing HGNS+AtoOxy, HGNS alone, AtoOxy alone, and placebo.

8 weeks
Multiple visits for each treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Atomoxetine-plus-oxybutynin (AtoOxy)
  • HGNS+AtoOxy
  • Unilateral hypoglossal nerve stimulation (HGNS)

Trial Overview

The study compares four treatments: HGNS plus atomoxetine and oxybutynin (AtoOxy), HGNS alone, AtoOxy alone, and placebo. Each participant tries all options in random order to see which works best at reducing sleep apnea events.

How Is the Trial Designed?

4

Treatment groups

Experimental Treatment

Group I: Sequence 4Experimental Treatment4 Interventions
Group II: Sequence 3Experimental Treatment4 Interventions
Group III: Sequence 2Experimental Treatment4 Interventions
Group IV: Sequence 1Experimental Treatment4 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials
1,694
Recruited
14,790,000+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41932835/

Atomoxetine plus oxybutynin for obstructive sleep apnoea

Conclusions: AtoOxy reduced AHI over 1 month; although the average response was not clinically meaningful, greater improvements were observed in ...

The Combination of Atomoxetine and Oxybutynin Greatly ...

Accordingly, pilot data collected after 1 week of therapy in six patients showed an 11% reduction in REM sleep on ato–oxy compared with placebo (P = 0.03). It ...

Atomoxetine Plus Oxybutynin for Obstructive Sleep Apnea

AtoOxy modestly reduced OSA severity per AHI over a 1-month treatment period. Greater improvements were evident in patients with a higher arousal threshold.

Efficacy of atomoxetine and oxybutynin in the treatment ...

We report in this manuscript an improvement of OSA severity with a greater reduction of 50% of AHI in two patients receiving atomoxetine and oxybutynin for 1 ...

Atomoxetine Plus Oxybutynin Improves Multiple Variables ...

Atomoxetine plus oxybutynin demonstrated efficacy in improving upper airway collapsibility, increasing breathing stability, and reducing the ...

Efficacy of atomoxetine and oxybutynin in the treatment ... - PMC

In two cases, the combination of atomoxetine and oxybutynin significantly reduced the severity of OSA and was well tolerated. Despite the ...

Effects of the Combination of Atomoxetine and Oxybutynin ...

Ato-oxy markedly improved the measures of upper airway collapsibility, increased breathing stability, and slightly reduced the arousal threshold.

Atomoxetine and Oxybutynin in Obstructive Sleep Apnea

The combination of atomoxetine and oxybutynin greatly reduces obstructive sleep apnea severity. A randomized, placebo-controlled, double-blind crossover trial.

Obstructive sleep apnea combination drug safe, reduces ...

A combination of atomoxetine and oxybutynin taken for 30 days lowered baseline obstructive sleep apnea severity, according to results published in Annals of ...