Clinical trial NCT02500342: Effect of Thyroid Hormone Replacement on Fatigability in Untreated Older Adults With Subclinical Hypothyroidism
Official title: Effect of Thyroid Hormone Replacement on Fatigability in Untreated Older Adults With Subclinical Hypothyroidism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Thyroid Dysfunction
Mental Fatigue
Fatigue
Keywords: Thyroid Dysfunction
Fatigue
Randomized Controlled Trial
Thyroxine
Hypothyroidism
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University College Cork
name: University of Lausanne Hospitals
First posted: 2015-07-16
Enrollment: 276
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Change from baseline in level of physical and mental fatigue as assessed by the Pittsburgh Fatigability Scale (PFS) score
timeFrame: At 1 year of follow-up
Secondary outcomes:
measure: Level of physical and mental fatigue as assessed by the PFS score
timeFrame: At baseline and at 1 year follow-up
Other outcomes:
Locations:
city: Cork
country: Ireland
facility: University College Cork, National University of Ireland
city: Lausanne
country: Switzerland
facility: Department of General Internal Medicine
state: Vaud
city: Bern
country: Switzerland
facility: Clinic for General Internal Medicine, Bern University Hospital Bern
Study officials:
affiliation: Clinic for General Internal Medicine, Bern University Hospital Bern
name: Nicolas Rodondi, MD MAS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007 May;92(5):1715-23. doi: 10.1210/jc.2006-1869. Epub 2007 Feb 13.
citation: Stuber MJ, Moutzouri E, Feller M, Del Giovane C, Bauer DC, Blum MR, Collet TH, Gussekloo J, Mooijaart SP, McCarthy VJC, Aujesky D, Westendorp R, Stott DJ, Glynn NW, Kearney PM, Rodondi N. Effect of Thyroid Hormone Therapy on Fatigability in Older Adults With Subclinical Hypothyroidism: A Nested Study Within a Randomized Placebo-Controlled Trial. J Gerontol A Biol Sci Med Sci. 2020 Sep 16;75(9):e89-e94. doi: 10.1093/gerona/glaa123.