1. Does Levothyroxine treatment for subclinical hypothyroidism give multi-modal benefits for the oldest old people with subclinical hypothyroidism?2. Are benefits seen across a wide range of outcomes, including prevention of cardiovascular disease,…
ID
Source
Brief title
Condition
- Thyroid gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in disease specific quality of life.
Secondary outcome
-General quality of life
-Handgrip strength
-Cognitive function, particularly executive function
-Total mortality and cardiovascular mortality
-Functional ability (basic Activities of Daily Living (ADL); extended
activities of daily living)
-Gait speed
-Haemoglobin
-Depressive symptoms
-Fatal and non-fatal cardiovascular events (this will include acute myocardial
infarction; stroke; amputations for peripheral vascular disease;
revascularisations for atherosclerotic vascular disease, including for acute
coronary syndrome and heart failure hospitalisations).
Background summary
Subclinical hypothyroidism is a common condition (8-18%) among older men and
women. Although by definition subclinical hypothyroidism 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 subclinical
hypothyroidism. 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. This is
especially the case for the oldest old, because observational studies are
conflicting and very few oldest old are included in clinical trials, although
they have the highest prevalence of subclinical hypothyroidism and its
potentially related symptoms and diseases.
Study objective
1. Does Levothyroxine treatment for subclinical hypothyroidism give multi-modal
benefits for the oldest old people with subclinical hypothyroidism?
2. Are benefits seen across a wide range of outcomes, including prevention of
cardiovascular disease, and improving health-related quality of life, muscle
function and cognition?
3. Are benefits seen in specific subgroups of oldest old people with SCH,
including women, and those with mild degrees of subclinical hypothyroidism (TSH
4.6-10 mU/L)?
4. Are any benefits offset by adverse effects, such as atrial fibrillation or
heart failure?
Study design
Randomised double-blind placebo-controlled parallel group trial
Intervention
Oral Levothyroxine 50 µg daily (reduced to 25 mcg daily in subjects < 50 kg
body weight or if known coronary heart disease) versus matching placebo.
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.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Community-dwelling patients aged over 80 years with SCH.;SCH is defined as persistently elevated TSH levels (TSH>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 or antithyroid medication (e.g. Carbimazole, methimazole, propylthiouracil, potassium percholate), 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 (within 4 weeks).
* Recent acute coronary syndrome, including myocardial infarction or unstable angina (within 4 weeks).
* Acute myocarditis ore acute pancarditis
* Untreated adrenal insufficiency or adrenal disorder
* Terminal illness.
* Patients known to have rare hereditary problem of galactose intolerance.
* 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 | EUCTR2012-004160-22-NL |
| ISRCTN | ISRCTNcandidateno14367 |
| CCMO | NL41259.058.13 |