Thyroid Hormone Replacement for Subclinical Hypothyroidism

Subclinical Hypothyroidism Clinical Trial

— TRUST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01660126
• Other study ID #: GN11GE272
• Secondary ID: 2011-004554-26
• Status: Completed
• Phase: Phase 4
• First received: August 6, 2012
• Last updated: March 9, 2017
• Start date: May 2014
• Est. completion date: November 18, 2016

Study information

• Verified date: March 2017
• Source: NHS Greater Glasgow and Clyde
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 737
• Est. completion date: November 18, 2016
• Est. primary completion date: November 18, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Hypothyroidism
• Subclinical Hypothyroidism

Intervention

Drug:
• Levothyroxine
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.
• Placebo

Locations

Country	Name	City	State
United Kingdom	Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde	Glasgow

Sponsors (5)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde	Leiden University Medical Center, University College Cork, University of Bern, University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thyroid-specific quality of life - Hypothyroid symptoms and Fatigue symptoms (co-primary outcomes)	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).	Measured at baseline and 12 months
Secondary	Health-related quality of life	The EuroQol5D	measured at baseline; 3 month; 12 month and final follow up (expected mean follow-up of 18 months).
Secondary	Handgrip strength	Handgrip strength measured using the Jadaar hand dynamometer.	Measured at baseline; 12 months and final follow up (expected mean follow-up of 18 months).
Secondary	Executive cognitive function	Letter Digit Coding Test [LDCT).	Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Secondary	Total mortality	Total mortality	Up to final follow up (expected mean follow-up of 18 months).
Secondary	Basic Activities of Daily Living	Basic Activities of Daily Living (ADL) measured using the 20-point Barthel Index [BI].	Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Secondary	Extended activities of daily living	Extended activities of daily living measured using the older American resources and services [OARS]) questionnaire	Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Secondary	Haemoglobin	Change in haemoglobin, measured on a full blood count	Measured at baseline and 1 year
Secondary	Fatal and non-fatal cardiovascular events	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.	Expected mean follow-up of 18 months.
Secondary	Generic thyroid specific quality of life	Thyroid-related quality of life Patient-Reported Outcome measure (ThyPRO) 39	Final follow-up
Secondary	Thyroid-specific quality of life - Hypothyroid symptoms	Change in hypothyroid symptom burden (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Hypothyroid symptoms domain).	Measured at 6-8 weeks and at final review
Secondary	Thyroid specific quality of life - Fatigue symptoms	Change in fatigue (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Fatigue and vitality domain).	Measured at 6-8 weeks and at final review