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Completed

NCT Number: NCT01660126

Thyroid Hormone Replacement for Subclinical Hypothyroidism

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.

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Key information

Conditions

Subclinical Hypothyroidism Cardiovascular Diseases

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde

Glasgow, G31 2ER, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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).

Treatment and study plan

Levothyroxine

Drug

The intervention will start with Levothyroxine 50 µg daily (reduced to 25 µg in subjects <50Kg body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) versus matching placebo; at 3 months if the serum TSH level is <0.4 mU/L dose will be reduced by 25 µg; TSH >=0.4 and <4.6 mU/L, no change to dose; TSH >=4.6mUL, additional 25 µg. 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 that will be prescribed is 150μg.

Other names: Thyroxine

Placebo

Drug

Primary outcomes

  1. Thyroid-specific quality of life - Hypothyroid symptoms and Fatigue symptoms (co-primary outcomes)

    Time frame: 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).

Secondary outcomes

  1. Health-related quality of life

    Time frame: measured at baseline; 3 month; 12 month and final follow up (expected mean follow-up of 18 months).

    The EuroQol5D

  2. Handgrip strength

    Time frame: Measured at baseline; 12 months and final follow up (expected mean follow-up of 18 months).

    Handgrip strength measured using the Jadaar hand dynamometer.

  3. Executive cognitive function

    Time frame: Measured at baseline and final follow-up (expected mean follow-up of 18 months).

    Letter Digit Coding Test [LDCT).

  4. Total mortality

    Time frame: Up to final follow up (expected mean follow-up of 18 months).

    Total mortality

  5. Basic Activities of Daily Living

    Time frame: Measured at baseline and final follow-up (expected mean follow-up of 18 months).

    Basic Activities of Daily Living (ADL) measured using the 20-point Barthel Index [BI].

  6. Extended activities of daily living

    Time frame: Measured at baseline and final follow-up (expected mean follow-up of 18 months).

    Extended activities of daily living measured using the older American resources and services [OARS]) questionnaire

  7. Haemoglobin

    Time frame: Measured at baseline and 1 year

    Change in haemoglobin, measured on a full blood count

  8. Fatal and non-fatal cardiovascular events

    Time frame: Expected mean follow-up of 18 months.

    This will include fatal and non fatal acute myocardial infarction and stroke; amputations for peripheral vascular disease; revascularisations for atherosclerotic vascular disease, including for acute coronary syndrome; heart failure hospitalisations.

  9. Generic thyroid specific quality of life

    Time frame: Final follow-up

    Thyroid-related quality of life Patient-Reported Outcome measure (ThyPRO) 39

  10. Thyroid-specific quality of life - Hypothyroid symptoms

    Time frame: Measured at 6-8 weeks and at final review

    Change in hypothyroid symptom burden (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Hypothyroid symptoms domain).

  11. Thyroid specific quality of life - Fatigue symptoms

    Time frame: Measured at 6-8 weeks and at final review

    Change in fatigue (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Fatigue and vitality domain).

Sponsors and collaborators

Lead sponsor

NHS Greater Glasgow and Clyde

Other

Collaborators

  • Leiden University Medical Center
  • University College Cork
  • University of Bern
  • University of Glasgow

Registry information

Official study title

Multi-modal Effects of Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism; a Randomised Placebo-controlled Trial

Acronym: TRUST

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Aug 8, 2012
Registry last updated
Mar 13, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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