Effect of Thyroid Hormone Replacement on Fatigability in Untreated Older Adults With Subclinical Hypothyroidism (TRUST FATIGUE)

March 28, 2019 updated by: University Hospital Inselspital, Berne
Thyroid hormone is a key regulatory hormone for a range of physiological systems. An impaired function of the thyroid gland such as subclinical hypothyroidism (SCH) can affect quality of life. Older adults with subclinical hypothyroidism often report non-specific symptoms such as tiredness. In addition, muscle symptoms such as cramps, weakness and myalgia are more common in SCH than in healthy controls. At present, evidence is lacking about the benefits of thyroxine replacement in the elderly with SCH, as no large randomized clinical trials (RCT) on the full range of relevant clinical outcomes, including tiredness have been performed. Moreover, there is continued uncertainty about the long-term impact on health related quality of life of thyroxine treatment for SCH. The aim of the study is to examine, within a large RCT of elderly participants with subclinical hypothyroidism, the impact of thyroxine therapy on the association between subclinical thyroid disease (SCTD) and the level of physical and mental fatigue. The existing trial infrastructure (TRUST thyroid trial-Euresearch FP7; clinicaltrials.gov ID: NCT 01660126) will be utilized to collect information on the level of physical and mental fatigue by using the Pittsburgh Fatigability Scale at baseline and at 1 year from 220 participants with persistent subclinical hypothyroidism randomized to either thyroxine or placebo.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background

Thyroid hormone is a key regulatory hormone for a range of physiological systems. An impaired function of the thyroid gland such as subclinical hypothyroidism (SCH) can affect quality of life. Older adults with subclinical hypothyroidism often report non-specific symptoms such as tiredness. In addition, muscle symptoms such as cramps, weakness and myalgia are more common in SCH than in healthy controls. At present, evidence is lacking about the benefits of thyroxine replacement in the elderly with SCH, as no large randomized clinical trials (RCT) on the full range of relevant clinical outcomes, including tiredness have been performed. Moreover, there is continued uncertainty about the long-term impact on health related quality of life of thyroxine treatment for SCH.

Objective

To examine, within a large RCT of elderly participants with subclinical hypothyroidism (the TRUST trial), the impact of thyroxine therapy on the association between subclinical thyroid disease (SCTD) and the level of physical and mental fatigue.

Methods

The existing trial infrastructure (TRUST thyroid trial-Euresearch FP7, clinicaltrials.gov ID: NCT 01660126) will be utilized to collect information on the level of physical and mental fatigue by using the Pittsburgh Fatigability Scale at baseline and at 1 year from 220 participants with persistent subclinical hypothyroidism randomized to either thyroxine or placebo.

Study Type

Interventional

Enrollment (Actual)

276

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ireland
      • Cork, Ireland, Cork
        • University College Cork, National University of Ireland
  • Switzerland
      • Bern, Switzerland, 3010
        • Clinic for General Internal Medicine, Bern University Hospital Bern
    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • Department of General Internal Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Community-dwelling patients aged >= 65 years with subclinical hypothyroidism
  • Written informed consent

Exclusion Criteria

  • Subjects currently under Levothyroxine or antithyroid drugs (amiodarone, lithium)
  • Recent thyroid surgery or radio-iodine (within 12 months)
  • Grade IV NYHA heart failure
  • Prior clinical diagnosis of dementia
  • Recent hospitalization for major illness or elective surgery (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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug: Levothyroxine
The intervention will start with Levothyroxine 50 mcg daily (reduced to 25 mcg in subjects <50 kg of body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) vs. matching placebo; at 3 months, if the serum TSH level is <0.4 mU/L, dose will be reduced by 25 mcg; TSH >=0.4 and <4.6 mU/L, no change to dose; TSH >=4.6 mU/L, additional 25 mcg. 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 which will be prescribed is 150 mcg (after 4 increments of 25 mcg at 3 months, 1, 2, 3 years; from the starting dose of 50 mcg).
Drug: Levothyroxine
The intervention will start with Levothyroxine 50 mcg daily (reduced to 25 mcg in subjects <50 kg of body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) vs. matching placebo; at 3 months, if the serum TSH level is <0.4 mU/L, dose will be reduced by 25 mcg; TSH >=0.4 and <4.6 mU/L, no change to dose; TSH >=4.6 mU/L, additional 25 mcg. 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 which will be prescribed is 150 mcg (after 4 increments of 25 mcg at 3 months, 1, 2, 3 years; from the starting dose of 50 mcg).
Placebo Comparator: Drug: Placebo

Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug.

Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg.
Drug: Placebo

Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug.

Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in level of physical and mental fatigue as assessed by the Pittsburgh Fatigability Scale (PFS) score
Time Frame: At 1 year of follow-up
At 1 year of follow-up

Secondary Outcome Measures

Outcome Measure
Time Frame
Level of physical and mental fatigue as assessed by the PFS score
Time Frame: At baseline and at 1 year follow-up
At baseline and at 1 year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

University of Lausanne Hospitals
University College Cork

Investigators

  • Principal Investigator: Nicolas Rodondi, MD MAS, Clinic for General Internal Medicine, Bern University Hospital Bern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

April 5, 2018

Study Completion (Actual)

April 5, 2018

Study Registration Dates

First Submitted

June 18, 2015

First Submitted That Met QC Criteria

July 13, 2015

First Posted (Estimate)

July 16, 2015

Study Record Updates

Last Update Posted (Actual)

March 29, 2019

Last Update Submitted That Met QC Criteria

March 28, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 162/11_2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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