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

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ClinicalTrials.gov Identifier: NCT02500342
Recruitment Status : Completed
First Posted : July 16, 2015
Last Update Posted : March 29, 2019
Sponsor:
Collaborators:
University College Cork
University of Lausanne Hospitals
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Thyroid Dysfunction Mental Fatigue Fatigue Drug: Levothyroxine Drug: Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Thyroid Hormone Replacement on Fatigability in Untreated Older Adults With Subclinical Hypothyroidism
Study Start Date : January 2014
Actual Primary Completion Date : April 5, 2018
Actual Study Completion Date : April 5, 2018

Resource links provided by the National Library of Medicine


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.





Primary Outcome Measures :
  1. 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 ]

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


Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02500342


Locations
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Ireland
University College Cork, National University of Ireland
Cork, Ireland, Cork
Switzerland
Department of General Internal Medicine
Lausanne, Vaud, Switzerland, 1011
Clinic for General Internal Medicine, Bern University Hospital Bern
Bern, Switzerland, 3010
Sponsors and Collaborators
University Hospital Inselspital, Berne
University College Cork
University of Lausanne Hospitals
Investigators
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Principal Investigator: Nicolas Rodondi, MD MAS Clinic for General Internal Medicine, Bern University Hospital Bern
Publications:
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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT02500342    
Other Study ID Numbers: 162/11_2
First Posted: July 16, 2015    Key Record Dates
Last Update Posted: March 29, 2019
Last Verified: March 2019
Keywords provided by University Hospital Inselspital, Berne:
Thyroid Dysfunction
Fatigue
Randomized Controlled Trial
Thyroxine
Hypothyroidism
Additional relevant MeSH terms:
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Thyroid Diseases
Hypothyroidism
Fatigue
Mental Fatigue
Endocrine System Diseases
Signs and Symptoms
Behavioral Symptoms