Clinical trial NCT01853579: The TRUST Study - Depression Substudy
Official title: Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) - Subanalysis on Subclinical Hypothyroidism and Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Subclinical Hypothyroidism
Depression
Keywords: Randomized controlled trial
Subclinical hypothyroidism
Levothyroxine
Depression
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
name: University of Bern
First posted: 2013-05-15
Enrollment: 426
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Mild thyroid failure is a common condition among older adults and has been associated with numerous adverse effects on health, such as cardiovascular disease, cognition disturbances and muscular problems. Mild thyroid failure has also been associated with an increased risk of developing depression. To date, only few studies have investigated the effect of thyroid hormone replacement on depression in patients with mild thyroid failure. This study therefore aims to assess whether thyroid hormone replacement in older adults with mild thyroid failure is associated with a decrease in the presence of depressive symptoms. This study forms a substudy of a large international study on thyroid hormone replacement in older adults with mild thyroid failure (the TRUST study).

Detailed description: Background

Subclinical hypothyroidism is a common condition among older adults, particularly above the age of 65 years, with a prevalence reaching 10 to 15% of the population. This condition has been associated with numerous adverse outcomes, such as cardiovascular disease, cognition disturbances and muscular problems. All of these potential outcomes will be assessed in the TRUST study. Subclinical hypothyroidism has also been associated with an increased risk of developing depression. It has been suggested that subclinical hypothyroidism may lower the threshold for the development of depression. The prevalence of depression among community-dwelling elderly ranges from 2 to 10%. Patients with depression have been shown to have a lower response to anti-depressive drugs when they have subclinical hypothyroidism. Only a few randomized studies in patients with subclinical hypothyroidism have studied the effect of thyroid hormone replacement on depression, with conflicting results: the studied populations were often small (maximal number of participants: 143), using different scales to measure the presence of depressive symptoms.

Objective

To investigate whether thyroid hormone replacement in older adults with subclinical hypothyroidism is associated with a decrease in the presence of depressive symptoms in a sub-study of the TRUST study.

Methods Use of the 15-item Geriatric Depression Scale (GDS-15) to measure depressive symptoms in all 450 patients included in the TRUST study in Switzerland and the Netherlands, the most validated test for depression screening, with validity to measure longitudinal changes. GDS-15 will be applied at baseline and after 1 year to compare changes in depression scores between placebo and thyroxin arms. Power calculation (ANCOVA method) with 225 participants per treatment group, assuming a standard deviation of 3 and a baseline to follow up correlation of 0.7, results in 99.9% power for detecting a mean difference of 1.0 points at a two-sided alpha-level of 0.05. Depending on recruitment for the main trial (ClinicalTrials.gov ID: NCT01660126) in respective countries, a lower number of participants may be included, retaining a very large power for this continuous outcome.

Eligibility criteria: Inclusion Criteria:

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

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)
* 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 15-items Geriatric Depression Scale
timeFrame: At 1 Year
Secondary outcomes:
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Lausanne
country: Switzerland
facility: Department of General Internal Medicine
state: Vaud
city: Bern
country: Switzerland
facility: University Clinic for General Internal Medicine, Bern University Hospital
Study officials:
affiliation: University Clinic of General Internal Medicine, Bern University Hospital, Bern, Switzerland
name: Nicolas Rodondi, MD, MAS
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center, Leiden, The Netherlands
name: Jacobijn Gussekloo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wildisen L, Feller M, Del Giovane C, Moutzouri E, Du Puy RS, Mooijaart SP, Collet TH, Poortvliet RKE, Kearney P, Quinn TJ, Kloppel S, Bauer DC, Peeters RP, Westendorp R, Aujesky D, Gussekloo J, Rodondi N. Effect of Levothyroxine Therapy on the Development of Depressive Symptoms in Older Adults With Subclinical Hypothyroidism: An Ancillary Study of a Randomized Clinical Trial. JAMA Netw Open. 2021 Feb 1;4(2):e2036645. doi: 10.1001/jamanetworkopen.2020.36645.