Energy Metabolism in Thyroidectomized Patients

甲状腺切除患者的能量代谢

基本信息

批准号：
10057417
负责人：
FRANCESCO S CELI
金额：
$ 21.15万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10057417
关键词：
Benign Body Composition Cardiovascular Physiology Cardiovascular system Clinical Clinical Trials Combined Modality Therapy Conflict (Psychology)Data Development Double-Blind Method Dyslipidemias Energy Metabolism Enzymes Experimental Models Functional disorder Genes Genetic Polymorphism Goiter High Prevalence Hormonal Hormone replacement therapy Hour Hypothyroidism In Vitro Indirect Calorimetry Institution Intervention Trial Iodide Peroxidase Knowledge Lipids Malignant neoplasm of thyroid Meta-Analysis Metabolic Metabolism Morbidity - disease rate Myocardial dysfunction Operative Surgical Procedures Participant Patient observation Patients Peripheral Phenotype Population Prevention Procedures Production Quality of life Randomized Replacement Therapy Reporting Research Design Residual state Risk Role Scheme Serum Solid Symptoms Therapeutic Thyroid Gland Thyroid Hormones Thyroidectomy Thyroxine Tissues Triiodothyronine Weight Weight Gain associated symptom autoimmune thyroid disease base cardiovascular endothelium cardiovascular risk factor comorbidity design effectiveness evaluation energy balance insight lipid metabolism multidisciplinary negative affect novel novel therapeutics personalized medicine prevent programs prospective reduce symptoms response standard of care tool

项目摘要

Hypothyroid symptoms despite adequate replacement therapy are common, and weight gain is one of the most frequently reported, negatively affecting quality of life. Combination therapy liothyronine/levothyroxine attempts to mimic the endogenous production of thyroid hormone have generated mixed results, mostly because of underpowered and not optimally designed studies. In this proposal we aim to study in detail patients undergoing total thyroidectomy before, and for a six-month period following the procedure while on levothyroxine only or on liothyronine/levothyroxine replacement therapy. We hypothesize that combination liothyronine/levothyroxine when compared to levothyroxine alone will minimize post- thyroidectomy weight gain and prevent the cardiovascular and lipid metabolism dysfunction associated with hypothyroidism. Post-surgical hypothyroidism is a unique experimental model to assess the metabolic effects of hypothyroidism and to compare different therapeutic schemes because: 1) patients can be studied before the procedure in a state of euthyroidism, 2) the onset of hypothyroidism is well defined hence its effects can be clearly defined, and 3) there is no residual endogenous production of thyroid hormone, as compared to autoimmune thyroid disease. These factors eliminate a significant amount of confounders, increasing the internal validity of the proposed study. Here we propose to conduct a proof-of-concept, controlled, double blind, parallel design study whereby patients with clinical indications to total thyroidectomy will undergo phenotype characterization at baseline before surgery while in a euthyroid state. Following surgery, patients will be randomized to levothyroxine alone (standard of care) or liothyronine/levothyroxine replacement therapy for a six-month period. Patients will undergo phenotype characterization at three and six months following surgery. We will assess body composition, 24-hour energy expenditure by whole room indirect calorimetry, cardiovascular function, and lipid metabolism. Additionally we will gather exploratory data on changes in quality of life and on the modulatory effects of a common polymorphism of the type 2 deiodinase gene which has been associated with differential response to thyroid hormone replacement therapy. Collectively, the data obtained from this proof-of-concept study will provide solid point estimates of the metabolic effects of post-surgical hypothyroidism and of differential (or lack thereof) response to liothyronine/levothyroxine replacement therapy. This in turn will provide the rationale whether pursuing the study hypotheses in a large intervention trial, and the tools to adequately power it to evaluate the effectiveness of combination therapy in the treatment of hypothyroidism and for the prevention of its effects on energy balance, cardiovascular system, lipid metabolism, and quality of life.

尽管有足够的替代疗法，但甲状腺功能减退症症状很常见，体重增加是最多的症状之一经常报告，对生活质量产生负面影响。联合疗法二甲氨酸/左甲状腺素试图模仿甲状腺激素的内源性产生的结果混合了结果，这主要是由于功能不足且没有最佳设计的研究。在此提案中，我们旨在详细研究以前接受甲状腺全切除术的患者，并在仅在左甲状腺素上或在氟甲甲状腺素/左甲状腺素/左甲状腺素替代疗法上进行六个月的时间进行研究。我们假设与单独的左甲状腺素相比，甲状腺素/左甲状腺素的组合将最大程度地减少甲状腺切除术后体重增加并预防心血管和脂质代谢与甲状腺功能减退症有关。甲状腺功能减退症是一个独特的实验模型，可以评估甲状腺甲状腺药物的代谢作用并比较不同的治疗方案，因为：1）可以研究患者，然后在甲状腺功能疗法状态下进行手术之前，2）甲状腺功能降低的效果是不明显的，因此可以清楚地确定其效果，并确定其构成的构成，并且是3）。自身免疫性甲状腺疾病。这些因素消除了大量的混杂因素，从而增加了拟议研究的内部有效性。在这里，我们建议进行概念验证，受控的双盲，平行设计研究，以便对甲状腺全切除术进行临床适应症的患者将在基线时在手术前进行表型表征，而处于甲状腺状态。手术后，患者将在六个月的时间内随机分为单独使用左甲状腺素（护理标准）或二甲状腺素/左甲状腺素替代疗法。患者将在手术后三个月和六个月内进行表型表征。我们将通过整个房间间接量热法，心血管功能和脂质代谢评估身体成分，24小时的能量消耗。此外，我们将收集有关生活质量变化的探索数据以及2型脱碘酶基因的常见多态性的调节作用，该基因与对甲状腺激素替代疗法的差异反应有关。总体而言，从这项概念验证研究中获得的数据将提供对手术后甲状腺功能减退症的代谢作用以及对利甲氨酸/左甲状腺素替代疗法的差异（或缺乏）反应的固定估计。反过来，这将提供基本原理，即是否在一项大型干预试验中提出研究假设，以及为IT提供足够动力的工具，以评估组合疗法在治疗甲状腺功能减退症治疗甲状腺功能减退症的有效性以及预防其对能量平衡，心血管系统，脂质代谢和生活质量的影响。