Phase I Study of Thyroid Hormone in Prematures

我们建议进行一项第一阶段试点研究，为#年甲状腺补充的第三阶段研究奠定基础。 评估这种治疗是否改善了妊娠28周前出生的婴儿的长期状况 结果，特别是智商和致残脑性瘫痪的风险。这项初步研究的目的是 建立达到新生儿最佳血浆激素目标所需的给药计划 在此期间，没有增加新生儿发病率、死亡率或生理功能障碍的措施。一个 特别的目标是避免因服用甲状腺而抑制促甲状腺激素。 荷尔蒙。我们还打算展示一个由五个参与者组成的国际财团之间的合作。 在启动试验之前，机构将涉及大约20个研究地点。六组，每组24名婴儿将 接受生理盐水对照、碘补充或四种甲状腺激素组合中的任何一种，不同于 类型(甲状腺激素联合三碘甲腺原氨酸)、剂量(4或8pg/kg/天)和给药途径 (团注或连续)。注册将在三个地点进行：威彻斯特医疗中心-纽约 纽约瓦尔哈拉医学院；阿姆斯特丹爱玛儿童医院学术医学中心 荷兰拉巴斯医院和西班牙马德里自治大学。甲状腺激素的测定 并将在特定时间获得研究对象及其母亲的碘状况，以及皮质醇水平 在婴儿身上。加州和西班牙的经验丰富的实验室将被用来评估激素和 分别为碘水平。一些与甲状腺相关的生理指标将被前瞻性地记录下来。 从医疗记录中找到的。已经制定了一项患者安全监测计划。数据将使用 并在密歇根州立大学数据协调中心进行了分析。最快 随着在研究人群中实现正常甲状腺功能的最佳模式变得清晰， 研究小组将申请后续的规划拨款，以制定 最终进行全面的多中心试验。

We propose a Phase 1 pilot study to set the stage for a Phase 3 study of thyroid supplementation in infants born prior to 28 weeks of gestation to assess whether such treatment improves long-term outcomes, specifically IQ and risk of disabling cerebral palsy. The purpose of the pilot study is to establish the dosing schedules needed to achieve the optimum plasma hormone targets in the neonatal period, without increasing measures of neonatal morbidity, mortality or physiological dysfunction. A particular goal is to avoid suppression of thyroid stimulating hormone from administration of thyroid hormone. We also aim to demonstrate cooperation among an international consortium of five participating institutions before initiating a trial to involve about 20 study sites. Six groups of 24 infants each will receive saline control, iodine supplementation, or any of four combinations of thyroid hormone, varying in type (thyroxine combined with tri-iodothyronine), dosage (4 or 8 pg/kg/day) and route of administration (bolus or continuous). Enrollment will take place in three sites: Westchester Medical Center-New York Medical College, Valhalla, NY; Emma Children's Hospital-Academic Medical Center, Amsterdam, the Netherlands; and Hospital La Paz-Autonomous University of Madrid, Spain. Measures of thyroid hormone and iodine status will be obtained at specific times on study subjects and their mothers, and cortisol levels in infants. Experienced laboratories in California and Spain will be employed for assessing hormones and iodine levels respectively. Several thyroid-related physiological measures will be prospectively recorded from medical records. A patient safety-monitoring plan has been developed. Data will be entered using a web-based system and analyzed at the data coordination center of Michigan State University. As soon as clarity is obtained on the optimum mode of achieving euthyroidemia in the study population, the research team will apply for a subsequent Planning Grant to develop the protocols and instruments for the eventual full-scale multicenter trial.