Clinical Trial: Thyroid Hormone Replacement for Subclinical Hypothyroidism

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary:
Sponsor: NHS Greater Glasgow and Clyde

Current Primary Outcome: 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).


Original Primary Outcome:

  • Fatal and non-fatal cardiovascular events [ Time Frame: Up to a maximum of 4 years ]
    This will include fatal and no fatal acute myocardial infarction and stroke; amputations for peripheral vascular disease; revascularisations for atherosclerotic vascular disease, including for acute coronary syndrome; heart failure hospitalisations.
  • Thyroid-specific quality of life [ Time Frame: Measured at baseline; 3 months; 12 months and close-out. ]
    Change in symptom burden and thyroid-specific QOL (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; symptom and fatigue domains only).


Current Secondary Outcome:

  • 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
  • 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.
  • Executive cognitive function [ Time Frame: Measured at baseline and final follow-up (expected mean follow-up of 18 months). ]
    Letter Digit Coding Test [LDCT).
  • Total mortality [ Time Frame: Up to final follow up (expected mean follow-up of 18 months). ]
    Total mortality
  • 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].
  • 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
  • Haemoglobin [ Time Frame: Measured at baseline and 1 year ]
    Change in haemoglobin, measured on a full blood count
  • 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.
  • Generic thyroid specific quality of life [ Time Frame: Final follow-up ]
    Thyroid-related quality of life Patient-Reported Outcome measure (ThyPRO) 39
  • 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).
  • 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).


Original Secondary Outcome:

  • Health-related quality of life [ Time Frame: measured at baseline; 3 month; 12 month and final follow up. ]
    The EuroQol5D
  • Handgrip strength [ Time Frame: Measured at baseline; 12 months and final follow up. ]
    Handgrip strength measured using the Jadaar hand dynamometer.
  • Executive cognitive function [ Time Frame: Measured at baseline and final follow-up. ]
    Letter Digit Coding Test [LDCT).
  • Total mortality [ Time Frame: Up to final follow up (maximum 4 years) ]
    Total mortality
  • Basic Activities of Daily Living [ Time Frame: Measured at baseline and final follow-up ]
    Basic Activities of Daily Living (ADL) measured using the 20-point Barthel Index [BI].
  • Extended activities of daily living [ Time Frame: Measured at baseline and final follow-up ]
    Extended activities of daily living measured using the older American resources and services [OARS]) questionnaire
  • Haemoglobin [ Time Frame: Measured at baseline and 1 year ]
    Change in haemoglobin, measured on a full blood count


Information By: NHS Greater Glasgow and Clyde

Dates:
Date Received: August 6, 2012
Date Started: May 2014
Date Completion:
Last Updated: March 9, 2017
Last Verified: March 2017