Phase I Study of Thyroid Hormone in Prematures

描述(由申请人提供)：我们建议进行一项第一阶段的试点研究，为妊娠28周前出生的婴儿进行第三阶段的甲状腺补充研究，以评估这种治疗是否改善了长期结果，特别是智商和致残脑瘫的风险。试点研究的目的是在不增加新生儿发病率、死亡率或生理功能障碍的措施的情况下，建立在新生儿期实现最佳血浆激素目标所需的剂量计划。一个特别的目标是避免由于服用甲状腺激素而抑制促甲状腺激素。我们还打算在启动一项涉及大约20个研究地点的试验之前，展示一个由五个参与机构组成的国际财团之间的合作。每组24名婴儿分为6组，分别接受生理盐水对照组、碘补充剂或四种甲状腺激素组合中的任何一种，不同类型(甲状腺激素与三碘甲腺原氨酸联合)、剂量(4或8 pg/kg/天)和给药途径(推注或持续)。注册将在三个地点进行：纽约州瓦尔哈拉的威彻斯特医学中心-纽约医学院；荷兰阿姆斯特丹的爱玛儿童医院-学术医学中心；西班牙马德里的拉巴斯自治大学医院。将在特定时间测量受试者及其母亲的甲状腺激素和碘状况，以及婴儿的皮质醇水平。加州和西班牙的经验丰富的实验室将分别用于评估激素和碘水平。几项与甲状腺相关的生理指标将从医疗记录中前瞻性地记录下来。已经制定了一项患者安全监测计划。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。一旦明确了在研究人群中实现正常甲状腺功能的最佳模式，研究小组将申请后续的规划拨款，以开发最终全面的多中心试验的方案和工具。

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. 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.