The TRUST Study - Depression Substudy
|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|
- Change from baseline in 15-items Geriatric Depression Scale [ Time Frame: At 1 Year ] [ Designated as safety issue: No ]
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||November 2017|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
Thyroxin Replacement Group
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
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01853579
|Contact: Nicolas Rodondi, MD, MAS||0041 (0) 31 632 41 email@example.com|
|Leiden University Medical Center||Recruiting|
|Leiden, Netherlands, 2300|
|Principal Investigator: Jacobijn Gussekloo, MD|
|Sub-Investigator: Wendy P den Elzen, PhD|
|Department of General Internal Medicine||Recruiting|
|Lausanne, Vaud, Switzerland, 1011|
|Principal Investigator: Nelly Pitteloud, MD|
|Sub-Investigator: Gerasimos Sykiotis, MD, PhD|
|University Clinic for General Internal Medicine, Bern University Hospital||Recruiting|
|Bern, Switzerland, 3010|
|Principal Investigator: Nicolas Rodondi, MD, MAS|
|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|