Levothyroxine Dosing in Older Individuals

老年人的左旋甲状腺素剂量

基本信息

批准号：
10638015
负责人：
ANNE R CAPPOLA
金额：
$ 59.16万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-15 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10638015
关键词：
Adult Age Atrial Fibrillation C-telopeptide Cardiovascular system Clinical Clinical Treatment Clinical Trials Cognitive Confidence Intervals Data Diabetes Mellitus Disease Dose Double-Blind Method Drug Prescriptions Elderly Frequencies Functional disorder Goals Guidelines Health Health Expenditures Health Status Hip Fractures Hypertension Hypoglycemia Hypotension Hypothyroidism Individual LDL Cholesterol Lipoproteins Laboratories Left Lipids Measures Medicare Memory Monitor Moods Musculoskeletal Observational Study Outcome Patient Outcomes Assessments Patients Persons Physiological Population Population Distributions Quality of life Questionnaires Randomized Reference Values Risk Risk Reduction Risk-Benefit Assessment Sleep Symptoms Testing Therapeutic Index Thyroid Diseases Thyroid Function Tests Thyroid Gland Thyroid Hormones Thyrotropin Thyroxine Titrations Weight aged blood pressure control bone turnover clinical practice clinically relevant cognitive function cognitive testing cost evidence base executive function flexibility glycemic control overtreatment peer pharmacologic primary outcome randomized placebo-controlled clinical trial secondary outcome

项目摘要

PROJECT SUMMARY Approximately 10% of US adults aged 65 years or older take levothyroxine to treat hypothyroidism. Guidance for its management has vast and important implications for the health and health care expenditures of millions of older people. Levothyroxine has a narrow therapeutic index that requires monitoring of dosing through thyroid stimulating hormone (TSH) testing. The current TSH reference range is based on the population distribution of younger people, despite evidence for a shift to higher levels with increasing age. Furthermore, observational data do not demonstrate adverse clinical consequences if people with TSH levels just above the reference range are left untreated, and a large clinical trial of people aged 65 years or older showed no benefit to treating this group of patients with levothyroxine. The trial of treatment of subclinical hypothyroidism used low doses of levothyroxine because of underlying endogenous thyroid function. These data may not be generalizable to individuals who have no endogenous thyroid function and rely entirely on exogenous levothyroxine. Small trials in younger people taking levothyroxine suggest that there are no physiologic differences between higher doses of levothyroxine that maintain TSH levels in the lower end of the reference range compared with lower doses of levothyroxine that maintain a TSH level just above the upper limit of the reference range. Our overall goal is to determine the clinical consequences that allowing greater flexibility in levothyroxine dosing would have in older individuals who take levothyroxine. We propose to perform a randomized, double-blind clinical trial of two 6-month dosing strategies of levothyroxine in patients aged 65 years and older who are already taking a stable dose of levothyroxine therapy, one to maintain a target TSH of 0.5-2.0 mU/L and another of a lower levothyroxine dose to achieve a target TSH of 5.5-7.0 mU/L. We will assess the effects of levothyroxine therapy at two different TSH targets on symptoms of hypothyroidism, mood, sleep, measures of memory and executive function, weight, lipids, and a marker of bone turnover. This clinical trial will provide essential data to inform the clinical value of increased flexibility in LT4 dosing for older LT4 users. Implications include widening the LT4 therapeutic window, decreasing the frequency of LT4 titration and TSH testing, and reducing the risk of LT4 overtreatment. In sum, this study could transform treatment of hypothyroidism into an easier, safer, and less costly clinical practice for millions of older adults.

项目概要大约 10% 的 65 岁或以上的美国成年人服用左甲状腺素来治疗甲状腺功能减退症。指导因为其管理对数百万人的健康和保健支出具有巨大而重要的影响老年人。左旋甲状腺素的治疗指数较窄，需要通过以下方式监测剂量：促甲状腺激素（TSH）测试。目前的TSH参考范围是根据人群尽管有证据表明随着年龄的增长，分布情况会向更高的水平转变。此外，观察数据并未表明，如果 TSH 水平略高于参考范围未得到治疗，针对 65 岁或以上人群的大型临床试验显示没有任何益处用左旋甲状腺素治疗这组患者。治疗亚临床甲状腺功能减退症的试验由于潜在的内源性甲状腺功能，低剂量的左旋甲状腺素。这些数据可能不是适用于没有内源性甲状腺功能并完全依赖外源性甲状腺功能的个体左旋甲状腺素。对服用左旋甲状腺素的年轻人进行的小型试验表明，服用左旋甲状腺素不会产生生理学影响。将 TSH 水平维持在参考值下限的较高剂量左旋甲状腺素之间的差异与维持 TSH 水平略高于上限的较低剂量的左旋甲状腺素相比，该范围参考范围。我们的总体目标是确定临床后果，从而允许更大的灵活性服用左旋甲状腺素的老年人的左旋甲状腺素剂量会有所不同。我们建议执行对 65 岁患者进行两种为期 6 个月的左旋甲状腺素给药策略的随机、双盲临床试验已接受稳定剂量左旋甲状腺素治疗的 1 岁及以上患者，该治疗可维持 TSH 目标 0.5-2.0 mU/L 和另一个较低的左甲状腺素剂量，以实现 5.5-7.0 mU/L 的目标 TSH。我们将评估左旋甲状腺素治疗两个不同 TSH 目标对甲状腺功能减退症、情绪、睡眠、记忆和执行功能测量、体重、血脂和骨转换指标。本临床试验将提供重要数据，以告知老年 LT4 增加 LT4 剂量灵活性的临床价值用户。影响包括扩大 LT4 治疗窗、降低 LT4 滴定频率以及 TSH 检测，并降低 LT4 过度治疗的风险。总之，这项研究可以改变治疗甲状腺功能减退症为数百万老年人提供了一种更简单、更安全、成本更低的临床实践。