Phase I Study of Thyroid Hormone in Prematures

我们提出了一项1期试点研究，为3期甲状腺补充剂研究奠定基础， 在妊娠28周之前出生的婴儿，以评估这种治疗是否能改善长期 结果，特别是智商和致残性脑瘫的风险。试点研究的目的是 建立新生儿达到最佳血浆激素目标所需的给药方案 在此期间，不增加新生儿发病率，死亡率或生理功能障碍的措施。一 一个特别的目的是避免甲状腺刺激激素的抑制， 激素.我们还旨在展示一个由五个参与的国际财团之间的合作 在开始试验之前，研究机构将涉及约20个研究中心。六组，每组24名婴儿， 接受生理盐水对照、碘补充剂或四种甲状腺激素组合中的任何一种， 类型（甲状腺素联合三碘甲状腺原氨酸）、剂量（4或8 pg/kg/天）和给药途径 （推注或连续）。入组将在三个研究中心进行：韦斯特切斯特医学中心-纽约约克 医学院，瓦尔哈拉，纽约;艾玛儿童医院学术医疗中心，阿姆斯特丹， 荷兰和西班牙马德里拉巴斯自治大学医院。甲状腺激素测量 将在特定时间获得研究受试者及其母亲的碘水平和皮质醇水平 在婴儿身上。将聘请加州和西班牙经验丰富的实验室评估激素， 碘水平分别。将前瞻性记录几项甲状腺相关生理指标 从医疗记录中。制定了患者安全监测计划。数据将使用 基于网络的系统，并在密歇根州立大学的数据协调中心进行分析。尽快 随着研究人群中获得甲状腺功能正常的最佳模式的明确， 研究团队将申请随后的规划补助金，以制定协议和工具， 最终的全面多中心试验。

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.