Multi-modal Effects of Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism; a Randomised Placebo-controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 737
- 试验地点
- 1
- 主要终点
- Thyroid-specific quality of life - Hypothyroid symptoms and Fatigue symptoms (co-primary outcomes)
研究概览
简要总结
Subclinical hypothyroidism (SCH) is a common condition among older men and women. Although by definition SCH comprises biochemically mild thyroid hormone deficiency without overt symptoms, it is a possible contributor to multiple problems in older age. Thyroid hormone has effects on numerous physiological systems, including the vascular tree, heart, skeletal muscle and brain. Therefore, thyroxine substitution to overcome thyroid hormone deficiency has the potential to give multisystem benefits to older people with SCH.
Small studies have reported reduced atherosclerosis and improved heart function with thyroxine replacement, but no large clinical trials have been performed. Therefore the available evidence is limited, leading to major variations in guidelines and clinical practice, with uncertainty regarding the indications for screening and treatment. The investigators propose a multicentre randomised placebo controlled trial to assess the impact of thyroxine replacement in a minimum of 540 older adults (maximum 750) with persisting SCH (excluding those in whom it is a temporary phenomenon who are unlikely to benefit). The investigators will include older men and women with a wide age range and of varying health status. Outcomes include health related quality of life, muscle strength, executive cognitive function and cardiovascular events, with a minimum of 1 year of follow up. Blood and urine samples will be stored in a biobank, to allow future research on causes of ill health in older people with SCH.
The investigators have the support of patient advocacy groups and a consortium with the wide range of expertise and experience required to conduct large scale multicentre clinical trials. The proposal explores the multisystem and quality of life benefits to older people of a tailored approach to management of SCH.
This clinical trial should definitively clarify whether thyroxine treatment for SCH provides benefits that are relevant for patients. This trial will provide strong evidence with the potential to improve clinical practice, reduce health care costs and promote healthy ageing of older adults.
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
- Double (Participant, Investigator)
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 (SCH).
- •SCH is defined as elevated TSH levels (>=4.6, <=19.9 mU/L) and free thyroxine (fT4) in reference range measured on a minimum of two occasions at least 3 months apart.
排除标准
- •Subjects currently on Levothyroxine or antithyroid drugs, amiodarone or lithium.
- •Recent thyroid surgery or radio-iodine (within 12 months).
- •Grade IV NYHA heart failure.
- •Prior clinical diagnosis of dementia.
- •Recent hospitalisation for major illness or elective surgery (within 4 weeks).
- •Recent acute coronary syndrome, including myocardial infarction or unstable angina (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).
研究组 & 干预措施
Levothyroxine
Oral Levothyroxine, starting dose 25 or 50 micrograms increased to a maximum of 150 micrograms once daily.
干预措施: Levothyroxine (Drug)
Placebo
Matched placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Thyroid-specific quality of life - Hypothyroid symptoms and Fatigue symptoms (co-primary outcomes)
时间窗: Measured at baseline and 12 months
Change in Hypothyroid Symptoms and Fatigue scores (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Hypothyroid symptoms and Fatigue domains).
次要结局
- Generic thyroid specific quality of life(Final follow-up)
- Health-related quality of life(measured at baseline; 3 month; 12 month and final follow up (expected mean follow-up of 18 months).)
- Handgrip strength(Measured at baseline; 12 months and final follow up (expected mean follow-up of 18 months).)
- Executive cognitive function(Measured at baseline and final follow-up (expected mean follow-up of 18 months).)
- Total mortality(Up to final follow up (expected mean follow-up of 18 months).)
- Basic Activities of Daily Living(Measured at baseline and final follow-up (expected mean follow-up of 18 months).)
- Extended activities of daily living(Measured at baseline and final follow-up (expected mean follow-up of 18 months).)
- Haemoglobin(Measured at baseline and 1 year)
- Fatal and non-fatal cardiovascular events(Expected mean follow-up of 18 months.)
- Thyroid-specific quality of life - Hypothyroid symptoms(Measured at 6-8 weeks and at final review)
- Thyroid specific quality of life - Fatigue symptoms(Measured at 6-8 weeks and at final review)
研究者
Professor David J Stott
David Cargill Professor of Geriatric Medicine
University of Glasgow