Main objective: To test the efficacy of thyroxine replacement for subclinical hypothyroidism (SCH) in older adults. Primary Objective: To determine multi-modal effects (quality of life; cognitive; musculoskeletal and cardiovascular) of levo-…
ID
Source
Brief title
Condition
- Thyroid gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in disease specific QOL and symptom burden
Secondary outcome
1) General QOL
2) Handgrip strength
3) Cognitive function
4) Total mortality
5) Functional ability (basic and extended activities of daily living)
6) Haemoglobin
7) Depressive symptoms
8) Fatal and non-fatal cardiovascular events
Background summary
Subclinical hypothyroidism (SCH) is a common condition (8-18%) among older men
and women. Although by definition SCH comprises biochemically mild thyroid
hormone deficiency, 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. Therefore, the aim of this study is to test the efficacy of
thyroxine replacement for subclinical hypothyroidism (SCH) in older adults to
provide the necessary evidence to properly inform best practice for treatment
of SCH in older people.
Study objective
Main objective: To test the efficacy of thyroxine replacement for subclinical
hypothyroidism (SCH) in older adults.
Primary Objective:
To determine multi-modal effects (quality of life; cognitive; musculoskeletal
and cardiovascular) of levo-thyroxine treatment for SCH in older adults.
Secondary objectives:
1) To determine effects of SCH treatment in various subgroups
2) To determine adverse effects associated with SCH treatment with particular
focus on arrhythmia and heart failure
3) To establish a blood bio-bank, to be used in future research into causes and
mechanisms of health, disease and disability in later life
Study design
Randomised double-blind placebo-controlled parallel group trial of
Levothyroxine for older people with subclinical hypothyroidism
Intervention
Oral Levothyroxine starting dose 50 µg daily (reduced to 25 µg daily in
subjects <50Kg body weight, or if known coronary heart disease) versus matching
placebo.
The dose will be changed according to the serum TSH level measured at 6-8 weeks
after starting medication and after each dose change. Dose titration will be
according to a predefined dosing schedule.
Study burden and risks
Adverse events (atrial fibrillation, heart failure and fractures in particular)
are likely to occur only in the context of over replacement of Levothyroxine.
Our dose titration scheme and study processes of careful monitoring of thyroid
function tests are designed to ensure we avoid prolonged periods of thyroid
hormone excess.
For the group allocated to placebo, there is risk of developing overt clinical
hypothyroidism* however, our study processes of careful monitoring of thyroid
function tests are designed to avoid this scenario.
Hippocratespad 21
Leiden 2333 ZD
NL
Hippocratespad 21
Leiden 2333 ZD
NL
Listed location countries
Age
Inclusion criteria
-Community-dwelling patients aged 65 years and over with subclinical hypothyroidism.
-Subclinical hypothyroidism is defined as persistently elevated TSH levels (><=4.6 and *19.9 mU/L) and free thyroxine (fT4) in reference range measured on a minimum of two occasions at least 3 months apart.
Exclusion criteria
-Subjects currently on Levothyroxine, antithyroid drugs, amiodarone or lithium.
-Recent thyroid surgery or radio-iodine therapy (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).
-Acute myocarditis or acute pancarditis
-Untreated adrenal insufficiency and adrenal disorder
-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 clinical trials of investigational medicinal products [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).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-004554-26-NL |
| ClinicalTrials.gov | NCT01660126 |
| CCMO | NL42067.058.12 |