Phase I Study of Thyroid Hormone in Prematures

描述（由申请人提供）： 我们提出了一项1期试点研究，为妊娠28周前出生的婴儿补充甲状腺的3期研究奠定基础，以评估这种治疗是否能改善长期结局，特别是智商和致残性脑瘫的风险。 初步研究的目的是确定在新生儿期达到最佳血浆激素目标所需的给药方案，而不增加新生儿发病率、死亡率或生理功能障碍的指标。 一个特别的目标是避免甲状腺激素给药抑制促甲状腺激素。 我们的目标还包括在启动涉及约20个研究地点的试验之前，展示由五个参与机构组成的国际财团之间的合作。 8组，每组20名婴儿将接受生理盐水对照、碘补充剂或甲状腺激素的6种组合中的任何一种，类型（甲状腺素单独或与三碘甲状腺原氨酸组合）、剂量（4或8 Ng/kg/天）和给药途径（推注或连续）不同。 入组将在三个研究中心进行：韦斯特切斯特医学中心-纽约州瓦尔哈拉的新约克医学院;艾玛儿童医院-荷兰阿姆斯特丹的学术医学中心;以及西班牙马德里自治大学的拉巴斯医院。将在特定时间测量研究受试者及其母亲的甲状腺激素和碘状态，以及婴儿的皮质醇水平。 将聘请加州和西班牙经验丰富的实验室分别评估激素和碘水平。 将从病历中前瞻性记录几项甲状腺相关生理指标。 制定了患者安全监测计划。 数据将使用基于网络的系统输入，并在密歇根州立大学的数据协调中心进行分析。 一旦明确了研究人群实现甲状腺功能正常的最佳模式，研究小组将申请规划拨款，为最终的全面多中心试验制定方案和工具。

DESCRIPTION (provided by the applicant): 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. Eight groups of 20 infants each will receive saline control, iodine supplementation, or any of six combinations of thyroid hormone, varying in type (Thyroxine alone or combined with Tri-Iodothyronine), dosage (4 or 8 Ng/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 the study population, the research team will apply for a planning grant to develop the protocols and instruments for the eventual full-scale multi-center trial.