Sleep Disordered Breathing With Opioid Use
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Hyperoxia, Acetazolamide.
- Who it may be relevant to
- Registry conditions: Sleep Apnea, Opioid Use, Sleep Disordered Breathing. Basic parameters: 18 years — 89 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Targeting Chemoreceptor Control of Breathing During Sleep to Mitigate Opioid-Associated Sleep Disordered Breathing
Overview
There is an increased risk for sleep disordered breathing (SDB), sleep-related hypoventilation and irregular breathing in individuals on chronic prescription opioid medications. Almost 30% of a veteran sleep clinic population had opioid-associated central sleep apnea (CSA). The proposal aims to identity whether oxygen and acetazolamide can be effective in reducing unstable breathing and eliminating sleep apnea in chronic opioid use via different mechanisms. We will study additional clinical parameters like quality of life, sleep and pain in patients with and without opioid use. This proposal will enhance the investigators' understanding of the pathways that contribute to the development of sleep apnea with opioid use. The investigators expect that the results obtained from this study will positively impact the health of Veterans by identifying new treatment modalities for sleep apnea.
Detailed description
In a national sample of Veterans, SDB was a significant risk factor for opioid-related toxicity and overdose; and the presence of CSA combined with chronic prescription opioid use compounded the mortality risk. There are only limited and partially effective therapies for this sleep disorder and the exact mechanisms by which opioids produce SDB in adults remain unclear, and varied and conflicting ventilatory control mechanisms have been suggested. This proposal will investigate whether alternative therapies can be developed by modulating specific physiologic mechanisms of ventilatory control. Specifically, the investigators will study effects of chronic oral prescription opioids on chemoresponsiveness and cerebrovascular responsiveness (CVR) (Aim 1); and whether interventions with sustained hyperoxia (Aim 2) and acetazolamide (Aim 3) will reduce the apneic threshold (AT) to alleviate breathing instability and SDB in chronic prescription opioid-associated SDB. The proposed aims will also allow us to delineate key mechanisms of breathing instability with opioid and without opioid use. The information garnered from the proposed experiments will drive development of novel personalized therapies to reduce SDB associated with chronic opioids in Veterans and, ultimately, will positively impact their long-term health and well-being.
Interventions
- Other Hyperoxia
The ventilatory effects of brief hyperoxia will be assessed by analyzing control breaths on room air immediately preceding the hyperoxic exposure, and comparing with the primary end-point, nadir minute ventilation breath, immediately following the brief hyperoxic exposure. - Drug Acetazolamide
Participants with sleep apnea will ingest capsules containing either placebo or acetazolamide 500 mg twice a day for 6 days. On the final 4 consecutive nights while still on ACZ, the investigators will perform i) physiology tests and ii) in-lab follow-up PSG.
Primary outcome measures
- Apneic threshold - a measure of breathing instability [Time frame: 2 days to 30 days]
- Cerebrovascular responsiveness to carbon-dioxide [Time frame: 7 days]
- Ventilatory responsiveness [Time frame: 2 days to 30 days]
- Carbon-dioxide reserve [Time frame: 2 days to 30 days]
Secondary outcome measures (1)
- Apnea hypopnea index [Time frame: 2 days to 30 days]
Eligibility criteria
Inclusion criteria
- Veterans, age 18-89 years
- Veterans with prescription opioids
Exclusion criteria
- Patients with BMI>40kg/m2 will be excluded to avoid the effects of morbid obesity on pulmonary mechanics and ventilatory control
- Patients with history of unresolved/untreated cardiac disease, including recent myocardial infarction, recent bypass surgery, untreated atrial and ventricular tachy-bradycardias
- Congestive heart failure with Cheyne-Stokes respiration (CSR)
- Current unstable angina
- Recent stroke
- Untreated schizophrenia
- Untreated hypothyroidism
- Unresolved seizure disorder
- Severe respiratory, neurological, liver and renal diseases
- Unstable psychiatric disorders/untreated PTSD
- Traumatic brain injury
- Pregnant women
- Significant sleep disorder such as narcolepsy, parasomnias disorder
- Failure to give informed consent
- Patients on tramadol and suboxone/buprenorphine
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Randomized
- Model
- Crossover
- Masking
- Single blind
- Primary purpose
- Other
Study locations
United States · 1 center
- John D. Dingell VA Medical Center, Detroit, MI — Detroit
Identifiers
NCT: NCT05589753 · PULM-003-18F · 1904002203