Subclinical HypothyroidismPhase 4TRUSTNCT01853579
The TRUST Study - Depression Substudy
A Phase 4 study testing Levothyroxine in people with Subclinical Hypothyroidism and Depression, run by Insel Gruppe AG, University Hospital Bern at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Subclinical Hypothyroidism, Depression
- What is being tested?
- Levothyroxine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 426 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Mar 2013to 5 Apr 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Community-dwelling patients aged >= 65 years with subclinical hypothyroidism
- Written informed consent
Who cannot join
- 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
Show all 9Show fewer
- 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)
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Switzerland2 sites
University Clinic for General Internal Medicine, Bern University Hospital
Bern, 3010
Department of General Internal Medicine
Lausanne, Canton of Vaud, 1011
About this study
Official title: 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).
Read the 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.
- Conditions
- Subclinical Hypothyroidism, Depression
- Being tested
- Levothyroxine, Placebo
- Keywords
- Randomized controlled trial, Subclinical hypothyroidism, Levothyroxine, Depression
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
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).
PlaceboDrug
Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug.
Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Experimental: Drug: Levothyroxine The intervention will start with Levothyroxine 50 mcg daily (reduced to 25 mcg in subjects <50 kg of body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) vs. matching placebo; at 3 months, if the serum TSH level is <0.4 mU/L, dose will be reduced by 25 mcg; TSH >=0.4 and <4.6 mU/L, no change to dose; TSH >=4.6 mU/L, additional 25 mcg. 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 which will be prescribed is 150 mcg (after 4 increments of 25 mcg at 3 months, 1, 2, 3 years; from the starting dose of 50 mcg). Receives: Drug: Levothyroxine |
| 2 | Placebo comparator | Placebo Comparator: Drug: Placebo Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug.
Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in 15-items Geriatric Depression Scale
Measured: At 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study startMar 2013
- Primary completion5 Apr 2018
- Study completion5 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Subclinical HypothyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 426 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center, University of Bern
- Responsible party
- Sponsor
- Investigators
- Nicolas Rodondi, MD, MAS, Principal investigator, University Clinic of General Internal Medicine, Bern University Hospital, Bern, SwitzerlandJacobijn Gussekloo, MD, Principal investigator, Leiden University Medical Center, Leiden, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01853579
- Sponsor's protocol ID
- 162/11
- Other IDs
- 2011-004554-26, 01660126
- Acronym
- TRUST
- Status last verified
- Jun 2018
- First submitted
- 6 May 2013
- Last updated
- 14 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 33566107
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) - Subanalysis on Subclinical Hypothyroidism and Depression
- ClinicalTrials.gov ID
- NCT01853579
- Acronym / sponsor ID
- TRUST / 162/11
- Conditions
- Subclinical Hypothyroidism, Depression
- Keywords
- Randomized controlled trial, Subclinical hypothyroidism, Levothyroxine, Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 426 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- Leiden University Medical Center, University of Bern
- Study start
- Mar 2013
- Primary completion
- 5 Apr 2018 (actual)
- Study completion
- 5 Apr 2018 (actual)
- First posted
- 15 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: LevothyroxineExperimental: Drug: Levothyroxine The intervention will start with Levothyroxine 50 mcg daily (reduced to 25 mcg in subjects <50 kg of body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) vs. matching placebo; at 3 months, if the serum TSH level is <0.4 mU/L, dose will be reduced by 25 mcg; TSH >=0.4 and <4.6 mU/L, no change to dose; TSH >=4.6 mU/L, additional 25 mcg. 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 which will be prescribed is 150 mcg (after 4 increments of 25 mcg at 3 months, 1, 2, 3 years; from the starting dose of 50 mcg). |
| 2 | Placebo comparator | Drug: PlaceboPlacebo Comparator: Drug: Placebo Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug. Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- Community-dwelling patients aged >= 65 years with subclinical hypothyroidism
- Written informed consent
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevothyroxineThe 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 | 1 |
| PlaceboControl patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug. Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg. | Drug | 2 |
Primary outcome
Change from baseline in 15-items Geriatric Depression Scale
Time frame: At 1 Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2018.
- Derived from this study: PubMed 33566107Wildisen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas Rodondi, MD, MAS principal investigator
University Clinic of General Internal Medicine, Bern University Hospital, Bern, Switzerland
Jacobijn Gussekloo, MD principal investigator
Leiden University Medical Center, Leiden, The Netherlands
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levothyroxine in people with Subclinical Hypothyroidism and Depression, run by Insel Gruppe AG, University Hospital Bern at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Switzerland, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in 15-items Geriatric Depression Scale (time frame: At 1 Year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01853579, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2018.