Novel Biomarkers and Skeletal Outcomes Associated With Subclinical Thyroid Dysfunction: a Prospective Evaluation and Impact of Treatment
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 145
- 试验地点
- 2
- 主要终点
- Change in bone mineral density (BMD)
研究概览
简要总结
Thyroid hormone is a key regulatory hormone for a range of physiological systems, including the skeleton. Previous studies have suggested that subclinical thyroid dysfunction (SCTD) may be associated with deleterious skeletal effects. However, controversy persists on the clinical relevance of SCTD as well as on optimal thresholds for treatment. Available data have substantial limitations: 1) limited prospective data are available to assess the associations between SCTD and non-cardiovascular outcomes, such as fractures 2) lack of data from large RCTs to investigate the pathophysiological mechanisms of associations between thyroid hormone and bone loss. The aim of the study is to examine the relationship between subclinical hypothyroidism and thyroid hormone replacement in regard to skeletal fragility, bone mineral density (BMD), bone loss and metabolism, and the risk of fractures in elderly participants. The listed parameters will be assessed by dual energy X ray absorptiometry (DXA) and novel bone imaging techniques at baseline, at 1 year of follow-up. The study will be nested in the TRUST trial (clinicaltrials.gov ID: NCT01660126), and will make use of its study infrastructure to determine bone biomarkers from biospecimens at baseline, and at 1 year of follow-up from 145 Swiss participants with persistent subclinical hypothyroidism randomized to either thyroxine or placebo in Bern and Lausanne.
详细描述
Background
Thyroid hormone is a key regulatory hormone for other physiological systems, including the skeleton. Previous studies have suggested that SCTD may be associated with deleterious skeletal effects. However, controversy persists on the clinical relevance of SCTD as well as on optimal thresholds for treatment. Available data have substantial limitations: 1) limited prospective data are available to assess the associations between SCTD and non-cardiovascular outcomes, such as fractures 2) lack of data from large RCTs to investigate the pathophysiological mechanisms of associations.
Objective
To examine, within a large RCT of elderly participants with subclinical hypothyroidism (the TRUST trial), the impact of thyroxine therapy on the association between SCTD and skeletal fragility, bone mineral density (BMD), bone loss and metabolism, and the risk of fractures.
Methods
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Community-dwelling patients aged >= 65 years with subclinical hypothyroidism
- •Written informed consent
- •Exclusion Criteria
- •Subjects currently under levothyroxine or antithyroid drugs (amiodarone, lithium)
- •Recent thyroid surgery or radio-iodine (within 12 months)
- •Grade IV NYHA heart failure
- •Prior clinical diagnosis of dementia
- •Recent hospitalization for major illness or elective surgery (within 4 weeks)
- •Terminal illness
- •Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
- •Subjects who are participating in ongoing RCTs of therapeutic interventions (including CTIMPs)
- •Plan to move out of the region in which the trial is being conducted within the next 2 years (proposed minimum follow-up period)
排除标准
- 未提供
研究组 & 干预措施
Drug: Levothyroxine
The intervention will start with Levothyroxine 50 mcg daily (reduced to 25 mcg in subjects <50 kg of body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) vs. matching placebo; at 3 months, if the serum TSH level is <0.4 mU/L, dose will be reduced by 25 mcg; TSH >=0.4 and <4.6 mU/L, no change to dose; TSH >=4.6 mU/L, additional 25 mcg. The process will be repeated at 12 months, then annually; mock titration will be performed in the placebo group. The maximum possible dose of Levothyroxine which will be prescribed is 150 mcg (after 4 increments of 25 mcg at 3 months, 1, 2, 3 years; from the starting dose of 50 mcg).
干预措施: Levothyroxine (Drug)
Drug: Placebo
Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug.
Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in bone mineral density (BMD)
时间窗: baseline and one year follow up
次要结局
- Bone mineral density (BMD)(1 year follow up)
- Change in bone biomarkers(baseline and one year follow up)