Thyroid Hormone Replacement for Subclinical Hypothyroidism

NCT ID: NCT01660126

Last Updated: 2017-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 737 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2016-11-18

Brief 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.

Conditions

Subclinical Hypothyroidism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Levothyroxine

Oral Levothyroxine, starting dose 25 or 50 micrograms increased to a maximum of 150 micrograms once daily.

Group Type: ACTIVE_COMPARATOR

Levothyroxine

Intervention Type: 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.

Placebo

Matched placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

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.

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Thyroxine

Eligibility Criteria

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).

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Glasgow

OTHER

Sponsor Role: collaborator

University College Cork

OTHER

Sponsor Role: collaborator

University of Bern

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role: lead

Responsible Party

Professor David J Stott

David Cargill Professor of Geriatric Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David J Stott, MBChB MD

Role: PRINCIPAL_INVESTIGATOR

University of Glasgow

Jacobijn Gussekloo, MD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Nicolas Rodondi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Bern

Patricia Kearney, MD

Role: PRINCIPAL_INVESTIGATOR

University College Cork

Rudi JG Westendorp, MD

Role: PRINCIPAL_INVESTIGATOR

University of Copenhagen

Locations

Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Countries

United Kingdom

References

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Other Identifiers

2011-004554-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GN11GE272

Identifier Type: -

Identifier Source: org_study_id