The TRUST Study - Depression Substudy

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University Hospital Inselspital, Berne
Sponsor:
Collaborators:
Leiden University Medical Center
University of Bern
Information provided by (Responsible Party):
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT01853579
First received: May 6, 2013
Last updated: June 11, 2014
Last verified: June 2014

May 6, 2013
June 11, 2014
March 2013
March 2017   (final data collection date for primary outcome measure)
Change from baseline in 15-items Geriatric Depression Scale [ Time Frame: At 1 Year ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01853579 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
The TRUST Study - Depression Substudy
Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) - Subanalysis on Subclinical Hypothyroidism and Depression

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).

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 1500 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 750 participants per treatment group, assuming a standard deviation of 3 and a baseline to follow up correlation of 0.7, results in 100% power for detecting a mean difference of 0.5 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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Subclinical Hypothyroidism
  • Depression
  • Drug: Levothyroxine
    The intervention will start with Levothyroxine 50 µg daily (reduced to 25 µg in subjects <50Kg body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) versus matching placebo; at 3 months if the serum TSH level is <0.4 mU/L dose will be reduced by 25 µg; TSH >=0.4 and <4.6 mU/L, no change to dose; TSH >=4.6mUL, additional 25 µg. 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 that will be prescribed is 150μg (after 4 increments of 25μg at 3 months, 1, 2 and 3 years; from the starting dose of 50μg).
  • Drug: Placebo
    Placebo
  • Experimental: 1
    Thyroxin Replacement Group
    Intervention: Drug: Levothyroxine
  • Placebo Comparator: 2
    Placebo Control Group
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1500
March 2017
March 2017   (final data collection date for primary outcome measure)

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)
Both
65 Years and older
No
Contact: Nicolas Rodondi, MD, MAS 0041 (0) 31 632 41 63 nicolas.rodondi@insel.ch
Netherlands,   Switzerland
 
NCT01853579
162/11, 2011-004554-26, 01660126
Yes
University Hospital Inselspital, Berne
University Hospital Inselspital, Berne
  • Leiden University Medical Center
  • University of Bern
Principal Investigator: Nicolas Rodondi, MD, MAS University Clinic of General Internal Medicine, Bern University Hospital, Bern, Switzerland
Principal Investigator: Jacobijn Gussekloo, MD Leiden University Medical Center, Leiden, The Netherlands
University Hospital Inselspital, Berne
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP