Morphine for Obstructive Sleep Apnea

(OIRD Trial)

Overseen By Danny J Eckert, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Brigham and Women's Hospital

Must not be taking: Opioids, Barbiturates, Benzodiazepines, others

Disqualifiers: Respiratory disorders, Pregnancy, Substance abuse, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how morphine, an opioid pain medication, affects breathing during sleep. Researchers aim to assess its impact on both healthy individuals and those with obstructive sleep apnea, a condition where breathing stops and starts during sleep. Participants must be either healthy sleepers or diagnosed with obstructive sleep apnea. As an Early Phase 1 trial, this research focuses on understanding how morphine affects breathing, providing participants an opportunity to contribute to foundational knowledge about its safety and effects.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants using medications that affect breathing, such as other opioids, barbiturates, benzodiazepines, and some antidepressants. It's important to discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that morphine is likely to be safe for humans?

Research shows that morphine can affect breathing by relaxing airway muscles, potentially leading to shallow breathing. Some studies suggest this could impact breathing, especially in people with obstructive sleep apnea (OSA). However, specific tests showed that morphine did not worsen sleep apnea in certain patients.

Opioids like morphine are linked to a higher risk of hospital visits due to breathing problems. Long-term opioid use in people with OSA might also increase the chance of developing central sleep apnea, a condition where breathing repeatedly stops and starts during sleep.

Since this trial is in its early phase, researchers are closely studying the treatment's safety in humans. Early phase trials focus on understanding treatment tolerance and identifying side effects. These factors are important to consider for those thinking about joining. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for obstructive sleep apnea, like CPAP machines and lifestyle changes, focus on managing airway obstruction. But morphine, the study drug, works differently. Researchers are excited because morphine may alter the body's response to carbon dioxide, potentially improving breathing patterns during sleep. This unique mechanism could offer a new avenue for treating sleep apnea beyond the typical mechanical or behavioral interventions. If successful, morphine might provide a novel option for patients who struggle with existing treatments.

What evidence suggests that morphine might be an effective treatment for obstructive sleep apnea?

This trial will compare the effects of morphine with a placebo in individuals with obstructive sleep apnea (OSA). Research has shown that morphine can affect breathing during sleep by relaxing throat muscles, leading to shallower breaths. This can impact airflow, especially in people with OSA. Some studies found that while morphine reduces the body's reaction to high carbon dioxide levels, it doesn't necessarily change how easily someone wakes up or the likelihood of airway collapse. Additionally, evidence suggests that opioids like morphine can disrupt breathing control during sleep, possibly causing more breathing pauses and lower oxygen levels. Overall, while morphine's effects on OSA are complex, it can alter breathing patterns in ways that might not benefit those with the condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Danny J Eckert, PhD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for healthy individuals and those with obstructive sleep apnea to study how opioids affect their breathing during sleep. Specific eligibility criteria are not provided, but typically include age range, health status, and absence of conditions that could interfere with the study.

Inclusion Criteria

Healthy controls: Apnea Hypopnea Index (AHI) < 5 events/hr on in-laboratory PSG within 3 months of enrollment

I have moderate to severe sleep apnea diagnosed within the last 3 months.

Exclusion Criteria

I have epilepsy or a history of seizures.

I have been diagnosed with a sleep disorder like restless legs, narcolepsy, or unusual behaviors during sleep.

History of allergy to lidocaine or oxymetazoline

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either morphine or placebo to study the impact on respiratory drive during sleep

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Morphine

Trial Overview The trial is testing the effects of Morphine taken orally (p.o.) compared to a placebo on respiratory drive during sleep in participants. It aims to understand the impacts of opioids on people with and without sleep apnea.

How Is the Trial Designed?

Group I: Morphine Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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

Effective clinical drug safety surveillance is crucial for protecting public health and ensuring the commercial success of pharmaceutical products, as it helps monitor and manage adverse drug events.

The process of drug safety surveillance is governed by FDA regulations and involves systematic management of adverse event reports, emphasizing the importance of clear communication and data handling to improve drug safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A primer of drug safety surveillance: an industry perspective. Part I: Information flow, new drug development, and federal regulations. Allan, MC.[2019]

The safety profile of medications can change after they are approved for public use, as new safety issues may arise that were not identified during clinical trials.

Regulatory agencies, like the FDA, actively monitor medication safety through various methods, including analyzing adverse experience reports and using large electronic databases to detect potential safety signals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring product safety in the postmarketing environment. Sharrar, RG., Dieck, GS.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03127800

Morphine in Moderate Obstructive Sleep Apnoea Morphine has been shown to reduce upper airway muscle tone and can also cause shallow breathing, which can affect breathing function in patients with sleep ...

2. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.9730

Opioids and obstructive sleep apnea The investigators showed a reduction in hypercapnic ventilatory response but no change in arousal threshold or upper airway collapsibility. Morphine blunted the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S000709122030653X

Intrathecal morphine and sleep apnoea severity in patients ... Intrathecal morphine did not increase sleep apnoea severity when measured using respiratory polygraphy. Of note, all patients had an increased number of apnoeic ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0269112

Association of obstructive sleep apnea and opioids use on ... The use of opioids and OSA was associated with the greatest hazard of all-cause hospitalizations and MVC requiring hospital or ED visit.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8805010/

Opioids and obstructive sleep apnea - PMC - PubMed Central Opioids affect control of breathing and impair upper airway function, causing central apneas, upper airway obstruction, and hypoxemia during sleep.

6. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.5704

Medium Increased Risk for Central Sleep Apnea but Not ... Conclusions: The meta-analysis results suggest that long-term opioid use in OSA patients has a medium effect on central sleep apnea.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7659468/

Postoperative Critical Events Associated with Obstructive ... This report analyzes cases submitted to the OSA Death and Near Miss Registry, focusing on factors associated with poor outcomes after an OSA-related event.