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
  Purpose

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).


Condition Intervention Phase
Subclinical Hypothyroidism
Depression
Drug: Levothyroxine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) - Subanalysis on Subclinical Hypothyroidism and Depression

Resource links provided by NLM:


Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:
  • Change from baseline in 15-items Geriatric Depression Scale [ Time Frame: At 1 Year ] [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: March 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Thyroxin Replacement Group
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).
Placebo Comparator: 2
Placebo Control Group
Drug: Placebo
Placebo

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 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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01853579

Contacts
Contact: Nicolas Rodondi, MD, MAS 0041 (0) 31 632 41 63 nicolas.rodondi@insel.ch

Locations
Netherlands
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2300
Principal Investigator: Jacobijn Gussekloo, MD         
Sub-Investigator: Wendy P den Elzen, PhD         
Switzerland
Department of General Internal Medicine Recruiting
Lausanne, Vaud, Switzerland, 1011
Principal Investigator: Nelly Pitteloud, MD         
Sub-Investigator: Tinh-Hai Collet, MD         
University Clinic for General Internal Medicine, Bern University Hospital Recruiting
Bern, Switzerland, 3010
Principal Investigator: Nicolas Rodondi, MD, MAS         
Sponsors and Collaborators
University Hospital Inselspital, Berne
Leiden University Medical Center
University of Bern
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT01853579     History of Changes
Other Study ID Numbers: 162/11, 2011-004554-26, 01660126
Study First Received: May 6, 2013
Last Updated: June 11, 2014
Health Authority: Switzerland: Ethikkommission
Switzerland: Swissmedic

Keywords provided by University Hospital Inselspital, Berne:
Randomized controlled trial
Subclinical hypothyroidism
Levothyroxine
Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Hypothyroidism
Behavioral Symptoms
Endocrine System Diseases
Mental Disorders
Mood Disorders
Thyroid Diseases

ClinicalTrials.gov processed this record on October 23, 2014