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

基本信息

批准号：
10491343
负责人：
DOROTHEA DENISE JENKINS
金额：
$ 124.8万
依托单位：
SPARK BIOMEDICAL INC
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10491343
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 Randomized Controlled Trials 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 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

项目摘要

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症 (NOWS) 是一种婴儿在阿片类药物戒断后出现戒断症状的病症。现在，婴儿在子宫内接触处方或非处方阿片类药物，如美沙酮或海洛因。中枢神经系统过度兴奋以及呼吸、胃肠道和植物神经症状。症状通常在出生后 48 至 72 小时内出现，截至 2012 年，每 25 例就有一名患有 NOWS 的婴儿出生。分钟在美国，占全国医疗保健支出超过 15 亿美元。 2012 年，全国 NOWS 比率从每 1000 名新生儿 1.2 例增加到每 1000 名新生儿 5.8 例，增加了 383%。经常需要住院新生儿重症监护病房 (NICU)，平均住院时间为 25 天平均治疗费用为 66,000 美元。目前，尚无用于管理 NOWS 的全国性护理标准。NOWS 的治疗通常遵循以下标准。多模式治疗以控制戒断和口服吗啡替代药物治疗为中心。然而，减少对神经毒性阿片类药物的需求的治疗是这一弱势群体的当务之急。事实上，一项针对 898 名婴儿的大型多中心随机研究表明，尽管吗啡在减轻疼痛的临床症状，但可能会导致严重的急性不良反应，例如心脏和神经系统的变化呼吸频率、低血压、鼻饲以及静脉补充营养的需要。鉴于人群的脆弱性和潜在的不利影响，吗啡应谨慎使用，谨慎地。美国儿科学会建议尝试使用非药物治疗，这包括将婴儿置于黑暗而安静的环境中、用襁褓、摇晃、母乳喂养以及提供除其他技术外，通过频繁少量喂食（称为“饮食”、“睡眠”、“控制台”或“ESC”）提供高热量营养。如果使用得当，这种非药物干预措施可以减少住院时间，治疗时长 (LOT)，以及已经使用NOWS 的婴儿的百分比。在阿片类药物戒断带来的压力下，非药物治疗可能会让这些患者受益匪浅，降低对额外药物的需求并可能减少住院时间。我们的第一阶段工作是第一项调查经皮耳廓神经刺激 (tAN) 效果的研究，作为口服吗啡的辅助治疗，可减少新生儿阿片类药物戒断体征和症状在所有研究参与者中，tAN 被证明是安全的、耐受性良好且有助于快速治疗。如果在未来的试验中证明安全有效，tAN 可能会扩大非药物作用。基于我们第一阶段的成功，我们建议使用我们的 Roo™ tAN 系统。作为减少与NOWS 相关的体征和症状的辅助疗法。