Delivering Transcutaneous Auricular Neurostimulation as an Adjunct Treatment for Neonatal Opioid Withdrawal Syndrome

经皮耳廓神经刺激作为新生儿阿片戒断综合征的辅助治疗

• 批准号: 10390149
• 负责人: DOROTHEA DENISE JENKINS
• 金额: $ 124.97万
• 依托单位: SPARK BIOMEDICAL INC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10390149
• 关键词: Academy; Accounting; Acupressure; Acupuncture Therapy; Acute; Adult; Adverse effects; Aftercare; American; Behavioral; Birth; Body Temperature; Body Weight decreased; Breast Feeding; Calories; Clinical; Clonidine; Collaborations; Crying; Data; Development; Devices; Diagnosis; Double-Blind Method; Ear; Eating; Enrollment; Environment; Exhibits; Exposure to; Future; Goals; Gold; Grant; Health Expenditures; Hearing Aids; Heart; Heroin; Hour; Hydrogels; Hypotension; Infant; Intervention; Intravenous; Lasers; Length; Length of Stay; Measurement; Measures; Medical; Medical Device; Medicine; Methadone; Morphine; Multi-Institutional Clinical Trial; Myelin; Neonatal Abstinence Syndrome; Neonatal Intensive Care Units; Nerve; Neural Pathways; Neuraxis; Neurologic; Newborn Infant; Nonpharmacologic Therapy; Opioid; Oral; Oxidative Stress; Pain; Participant; Patients; Pediatrics; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phenobarbital; Randomized; Signs and Symptoms; Sleep; Sleep disturbances; South Carolina; Stress; Symptoms; System; Techniques; Technology; Testing; Therapeutic; Time; Treatment Cost; Tremor; Trigeminal System; Universities; University Hospitals; Vomiting; Vulnerable Populations; Weaning; Withdrawal; Withdrawal Symptom; associated symptom; base; bioelectricity; clinical effect; control trial; experience; external ear auricle; gastrointestinal; in utero; multimodality; nasogastric feeding; neonate; neurobehavior; neurobehavioral; neurodevelopment; neuron apoptosis; neuroregulation; neurotoxic; nutrition; opioid withdrawal; phase 1 study; phase 2 study; prenatal exposure; respiratory; side effect; skin irritation; standard of care; success; tool; treatment effect; treatment group; trial design; white matter injury

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition in which infants undergo withdrawal after exposure to prescription or non-prescription opioids such as methadone or heroin in utero. NOWS babies exhibit hyperirritability of the central nervous system and respiratory, gastrointestinal, and autonomic symptoms. These symptoms usually appear within 48 to 72 hours after birth. As of 2012, an infant with NOWS was born every 25 minutes in the US, accounting for more than $1.5 billion in national healthcare expenditures. Between 2000– 2012, national rates of NOWS increased 383% from 1.2 per 1000 births to 5.8 per 1000 births. These infants frequently require hospital stay in a neonatal intensive care unit (NICU) with an average hospital stay of 25 days at an average treatment cost of $66K. Currently, no nationwide standard of care exists for managing NOWS. Treatment of NOWS usually follows a multimodal regime centered on controlled withdrawal and replacement drug therapy with oral morphine. However, treatments that reduce the need for neurotoxic opioids are a high priority in this vulnerable population. In fact, a large multicenter randomized study of 898 infants demonstrated that, although morphine is effective in decreasing clinical signs of pain, it can cause significant acute adverse effects such as changes in heart and respiratory rate, hypotension, nasogastric feeds, and need for intravenous supplemental nutrition. Based on the vulnerability of the population and the potential for adverse effects, morphine should be used judiciously and cautiously. The American Academy of Pediatrics recommends attempting the use of non-pharmacologic treatment, which includes placing the infant in a dark and quiet environment, swaddling, rocking, breastfeeding, and providing high-calorie nutrition in frequent small feedings (known as Eat, Sleep, Console or ESC), among other techniques. When used appropriately, such non-pharmacological interventions have resulted in a reduction in length of stay, length of treatment (LOT), and percentage of infants requiring pharmacotherapy. With NOWS babies already under stress from opioid withdrawal, a non-pharmacological treatment may greatly benefit these patients, lowering the need for additional medications and potentially reducing their hospital stay. Our Phase I effort was the first study investigating the effects of transcutaneous auricular neurostimulation (tAN), as an adjunct therapy to oral morphine, in the reduction of the opioid withdrawal signs and symptoms in newborns with NOWS. Across all study participants, tAN was shown to be safe, well-tolerated, and facilitate the rapid weaning of oral morphine. If proven safe and effective in future trials, tAN may expand non-pharmacological treatment options for these infants. Building on our Phase I success, we propose to use our Roo™ tAN system as an adjunct therapy to reduce the signs and symptoms associated with NOWS.

新生儿阿片类药物戒断综合征（NOWS）是一种婴儿在服用阿片类药物后戒断的疾病。 在子宫内暴露于处方或非处方阿片类药物，如美沙酮或海洛因。NOWS婴儿展 中枢神经系统的过敏和呼吸、胃肠道和自主神经症状。这些 症状通常在出生后48至72小时内出现。截至2012年，每25个新生儿中就有一个患有NOWS 在美国，这一数字超过15亿美元。在2000- 2012年，全国新生儿死亡率从每1000名新生儿1.2人上升到每1000名新生儿5.8人，增长了383%。这些婴儿 经常需要在新生儿重症监护室（NICU）住院，平均住院时间为25天 平均治疗费用为6.6万美元。 目前，没有全国性的护理标准来管理NOWS。NOWS的治疗通常遵循 多模式方案集中于控制戒断和口服吗啡替代药物治疗。 然而，减少对神经毒性阿片类药物需求的治疗是这一脆弱人群的高度优先事项。 事实上，一项对898名婴儿进行的大型多中心随机研究表明，尽管吗啡对 减少疼痛的临床体征，它可能会导致显著的急性不良反应，如心脏的变化， 呼吸频率、低血压、鼻饲和需要静脉补充营养。基于 鉴于人群的脆弱性和潜在的不良反应，应谨慎使用吗啡， 谨慎地 美国儿科学会建议尝试使用非药物治疗， 包括将婴儿放在黑暗安静的环境中，用襁褓包裹，摇晃，母乳喂养， 高热量营养在频繁的小喂养（称为吃，睡眠，控制台或ESC），以及其他技术。 如果使用得当，这种非药物干预措施可缩短住院时间， 治疗时间（LOT）和需要药物治疗的婴儿百分比。NOWS婴儿已经 在阿片样物质戒断的压力下，非药物治疗可能极大地有益于这些患者， 降低对额外药物的需求，并可能减少他们的住院时间。 我们的第一阶段工作是第一项研究经皮耳神经刺激（tAN）的影响， 作为口服吗啡的辅助治疗，减少新生儿阿片类药物戒断体征和症状 关于NOWS在所有的研究参与者中，tAN被证明是安全的，耐受性良好，并促进快速的 停用口服吗啡如果在未来的试验中证明安全有效，tAN可能会扩大非药物治疗， 为这些婴儿提供治疗方案。在第一阶段成功的基础上，我们建议使用我们的Roo™ tAN系统 作为一种辅助治疗，以减少与NOWS相关的体征和症状。