Targeting Chemoreceptor Control of Breathing During Sleep to Mitigate Opioid-Associated Sleep Disordered Breathing
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Cerebrovascular responsiveness to carbon-dioxide
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Veterans, age 18-89 years
- •Veterans with prescription opioids
排除标准
- •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
研究组 & 干预措施
Hyperoxia
Determine the effect of sustained hyperoxia overnight vs room air overnight on ventilatory control during sleep, including the apneic threshold, carbon-dioxide reserve and chemosensitivity measured via pressure support ventilation (PSV) during non-rapid eye movement sleep (NREM) sleep.
干预措施: Hyperoxia (Other)
Acetazolamide (ACZ)
Determine the effect of acetazolamide on cerebrovascular responsiveness to CO2 during wake and sleep. Participants will receive oral ACZ therapy for 6 days, While on the medication following studies will be performed - experimental night study, experimental day study, polysomnography night study (PSG).
干预措施: Acetazolamide (Drug)
结局指标
主要结局
Cerebrovascular responsiveness to carbon-dioxide
时间窗: 7 days
Cerebrovascular response to different levels of CO2: this is a measure of the response of the cerebral blood flow to changes in carbon dioxide levels and is used as a measure of ventilatory control of breathing
Carbon -dioxide reserve
时间窗: 2 days to 30 days
This is a derived measure. This is calculated as the difference between the apneic threshold PETCO2 (given above) and the control PETCO2.
Apneic threshold- a measure of breathing instability
时间窗: 2 days to 30 days
Measures of breathing instability including: Apneic threshold: this is the end-tidal Co2 at which a central apnea closes to a hypopnea is produced.
Ventilatory responsiveness
时间窗: 2 days to 30 days
Hypocapnic ventilatory response; this is calculated as the change in minute ventilation for corresponding changes in PETCO2.
Apneic threshold - a measure of breathing instability
时间窗: 2 days to 30 days
Measures of breathing instability including: Apneic threshold: this is the end-tidal Co2 at which a central apnea closes to a hypopnea is produced.
Carbon-dioxide reserve
时间窗: 2 days to 30 days
This is a derived measure. This is calculated as the difference between the apneic threshold PETCO2 (given above) and the control PETCO2.
次要结局
- Apnea hypopnea index(2 days to 30 days)