Treating Residual OSA With Endotype-directed Pharmacotherapy (Aim 3)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Apnea Hypopnea Index (AHI, Events/Hour of Sleep)
研究概览
简要总结
Persistent obstructive sleep apnea (OSA) is common in people treated with mandibular advancement device (MAD) or hypoglossal nerve stimulation (HGNS). For most patients, these treatments are the last line of defense. If MAD or HGNS do not work, then patients are left to suffer the consequences of undertreated OSA. In this study, the investigators want to test the addition of a drug treatment to their regimen. Endotypes will be targeted pharmacologically with one of the following drugs: acetazolamide for a high loop gain, atomoxetine-plus-eszopiclone for poor pharyngeal muscle compensation, or trazodone for a low arousal threshold.
This aim is expected to provide treatment strategies for rescuing non-responders to MAD or HGNS therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals who have failed MAD or HGNS therapy, defined as a residual AHI ≥ 15 events/hr on MAD or HGNS therapy.
排除标准
- •Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:
- •central sleep apnea (>50% of respiratory events scored as central), chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.
- •Other sleep disorders: periodic limb movements (periodic limb movement index > 20/hr), narcolepsy, or parasomnias.
- •Any unstable major medical condition.
- •Medications expected to stimulate or depress respiration (including opioids, barbiturates, benzodiazepines, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
- •Use of SSRIs/SNRIs.
- •Contraindications for atomoxetine, including:
- •pheochromocytoma
- •use of monoamine oxidase inhibitors
- •benign prostatic hypertrophy, urinary retention
- •untreated narrow angle glaucoma
- •bipolar disorder, mania, psychosis
- •clinically significant constipation, gastric retention
- •pre-existing seizure disorders
- •clinically-significant kidney disorders
- •clinically-significant liver disorders
- •clinically-significant cardiovascular conditions
- •severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline)
- •cardiomyopathy (LVEF<50%) or heart failure
- •advanced atherosclerosi
- •history of cerebrovascular events
- •history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation
- •other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate
- •myasthenia gravis
- •pregnancy/breast-feeding
- •Contraindications for eszopiclone, including:
- •Hypersensitivity to eszopiclone
- •Chronic Obstructive Pulmonary Disease (COPD)
- •Pregnancy
- •Breast feeding
- •Liver disease
- •Contraindications for acetazolamide, including:
- •Hyperchloremic acidosis
- •Hypokalemia
- •Hyponatremia
- •Adrenal insufficiency
- •Impaired kidney function
- •Hypersensitivity to acetazolamide or other sulfonamides.
- •Marked liver disease or impairment of liver function, including cirrhosis.
- •Contraindications for trazodone, including:
- •suicidal ideation
- •bipolar disorder, mania
- •use of monoamine oxidase inhibitors
- •coronary artery disease
- •cardiac arrhythmias
- •QT prolongation
- •hepatic disease
- •renal failure or impairment
- •closed angle glaucoma
- •pregnancy/breast-feeding
研究组 & 干预措施
Placebo
This is a two arm study. Patients will receive only one of the following drugs based on their altered sleep apnea trait. Patients with decreased arousal threshold will undergo treatment with placebo or Trazodone 100 mg in random order (one pill before 30 minutes before bedtime), patients with decreased pharyngeal muscle responsiveness will undergo treatment with placebo or Atomoxetine 80 mg + Eszopiclone 3 mg in random order (one pill before 30 minutes before bedtime), patients with increased loop gain will undergo treatment with placebo or Acetazolamide 500 mg in random order (one pill before 30 minutes before bedtime).
干预措施: Placebo (Drug)
Interventional arm
This is a two arm study. Patients will receive only one of the following drugs based on their altered sleep apnea trait. Patients with decreased arousal threshold will undergo treatment with placebo or Trazodone 100 mg in random order (one pill before 30 minutes before bedtime), patients with decreased pharyngeal muscle responsiveness will undergo treatment with placebo or Atomoxetine 80 mg + Eszopiclone 3 mg in random order (one pill before 30 minutes before bedtime), patients with increased loop gain will undergo treatment with placebo or Acetazolamide 500 mg in random order (one pill before 30 minutes before bedtime).
干预措施: Atomoxetine and eszopiclone (Drug)
Interventional arm
This is a two arm study. Patients will receive only one of the following drugs based on their altered sleep apnea trait. Patients with decreased arousal threshold will undergo treatment with placebo or Trazodone 100 mg in random order (one pill before 30 minutes before bedtime), patients with decreased pharyngeal muscle responsiveness will undergo treatment with placebo or Atomoxetine 80 mg + Eszopiclone 3 mg in random order (one pill before 30 minutes before bedtime), patients with increased loop gain will undergo treatment with placebo or Acetazolamide 500 mg in random order (one pill before 30 minutes before bedtime).
干预措施: Acetazolamide (Drug)
Interventional arm
This is a two arm study. Patients will receive only one of the following drugs based on their altered sleep apnea trait. Patients with decreased arousal threshold will undergo treatment with placebo or Trazodone 100 mg in random order (one pill before 30 minutes before bedtime), patients with decreased pharyngeal muscle responsiveness will undergo treatment with placebo or Atomoxetine 80 mg + Eszopiclone 3 mg in random order (one pill before 30 minutes before bedtime), patients with increased loop gain will undergo treatment with placebo or Acetazolamide 500 mg in random order (one pill before 30 minutes before bedtime).
干预措施: Trazodone (Drug)
结局指标
主要结局
Apnea Hypopnea Index (AHI, Events/Hour of Sleep)
时间窗: 1 night
Based on previous studies the investigators anticipate that the interventional arm will reduce AHI through a positive effect on the abnormal endotype.
次要结局
- Arousal Index (AI, Events/Hours of Sleep)(1 night)
- Nadir oxygen saturation during sleep (LSpO2, %)(1 night)
研究者
David Andrew Wellman
Associate Professor of Medicine
Brigham and Women's Hospital