Subclinical HypothyroidismPhase 4TRUSTNCT01660126
Thyroid Hormone Replacement for Subclinical Hypothyroidism
A Phase 4 study testing Levothyroxine in people with Subclinical Hypothyroidism, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.
Trial summary
Subclinical hypothyroidism (SCH) is a common condition among older men and women. Although by definition SCH comprises biochemically mild thyroid hormone deficiency without overt symptoms, it is a possible contributor to multiple problems in older age. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Subclinical Hypothyroidism
- 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
- 737 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2014to 18 Nov 2016
- 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 (SCH).
- SCH is defined as elevated TSH levels (>=4.6, <=19.9 mU/L) and free thyroxine (fT4) in reference range measured on a minimum of two occasions at least 3 months apart.
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).
- Recent acute coronary syndrome, including myocardial infarction or unstable angina (within 4 weeks).
Show all 10Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde
Glasgow, G31 2ER
About this study
Official title: Multi-modal Effects of Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism; a Randomised Placebo-controlled Trial
Subclinical hypothyroidism (SCH) is a common condition among older men and women. Although by definition SCH comprises biochemically mild thyroid hormone deficiency without overt symptoms, it is a possible contributor to multiple problems in older age. Thyroid hormone has effects on numerous physiological systems, including the vascular tree, heart, skeletal muscle and brain. Therefore, thyroxine substitution to overcome thyroid hormone deficiency has the potential to give multisystem benefits to older people with SCH.
Small studies have reported reduced atherosclerosis and improved heart function with thyroxine replacement, but no large clinical trials have been performed. Therefore the available evidence is limited, leading to major variations in guidelines and clinical practice, with uncertainty regarding the indications for screening and treatment. The investigators propose a multicentre randomised placebo controlled trial to assess the impact of thyroxine replacement in a minimum of 540 older adults (maximum 750) with persisting SCH (excluding those in whom it is a temporary phenomenon who are unlikely to benefit). The investigators will include older men and women with a wide age range and of varying health status. Outcomes include health related quality of life, muscle strength, executive cognitive function and cardiovascular events, with a minimum of 1 year of follow up. Blood and urine samples will be stored in a biobank, to allow future research on causes of ill health in older people with SCH.
Read more
The investigators have the support of patient advocacy groups and a consortium with the wide range of expertise and experience required to conduct large scale multicentre clinical trials. The proposal explores the multisystem and quality of life benefits to older people of a tailored approach to management of SCH.
This clinical trial should definitively clarify whether thyroxine treatment for SCH provides benefits that are relevant for patients. This trial will provide strong evidence with the potential to improve clinical practice, reduce health care costs and promote healthy ageing of older adults.
- Conditions
- Subclinical Hypothyroidism
- Being tested
- Levothyroxine, Placebo
- Keywords
- Aged, Cardiovascular disease, Levothyroxine, Randomised controlled trial, Quality of life, Subclinical hypothyroidism
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
Also called Thyroxine
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.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Levothyroxine | Active comparator | Oral Levothyroxine, starting dose 25 or 50 micrograms increased to a maximum of 150 micrograms once daily. Receives: Drug: Levothyroxine |
| Placebo | Placebo comparator | Matched placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thyroid-specific quality of life - Hypothyroid symptoms and Fatigue symptoms (co-primary outcomes)
Change in Hypothyroid Symptoms and Fatigue scores (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Hypothyroid symptoms and Fatigue domains).
Measured: Measured at baseline and 12 months
Secondary outcomes (11)
Health-related quality of life
The EuroQol5D
Measured: measured at baseline; 3 month; 12 month and final follow up (expected mean follow-up of 18 months).
Handgrip strength
Handgrip strength measured using the Jadaar hand dynamometer.
Measured: Measured at baseline; 12 months and final follow up (expected mean follow-up of 18 months).
Executive cognitive function
Letter Digit Coding Test [LDCT).
Measured: Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Total mortality
Total mortality
Measured: Up to final follow up (expected mean follow-up of 18 months).
Basic Activities of Daily Living
Basic Activities of Daily Living (ADL) measured using the 20-point Barthel Index [BI].
Measured: Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Extended activities of daily living
Extended activities of daily living measured using the older American resources and services [OARS]) questionnaire
Measured: Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Haemoglobin
Change in haemoglobin, measured on a full blood count
Measured: Measured at baseline and 1 year
Fatal and non-fatal cardiovascular events
This will include fatal and non fatal acute myocardial infarction and stroke; amputations for peripheral vascular disease; revascularisations for atherosclerotic vascular disease, including for acute coronary syndrome; heart failure hospitalisations.
Measured: Expected mean follow-up of 18 months.
Generic thyroid specific quality of life
Thyroid-related quality of life Patient-Reported Outcome measure (ThyPRO) 39
Measured: Final follow-up
Thyroid-specific quality of life - Hypothyroid symptoms
Change in hypothyroid symptom burden (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Hypothyroid symptoms domain).
Measured: Measured at 6-8 weeks and at final review
Thyroid specific quality of life - Fatigue symptoms
Change in fatigue (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Fatigue and vitality domain).
Measured: Measured at 6-8 weeks and at final review
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2012 (estimated)
- Study startMay 2014
- Primary completion18 Nov 2016
- Study completion18 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 737 participants (actual)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow, University College Cork, University of Bern, Leiden University Medical Center
- Responsible party
- Principal investigator, Professor David J Stott, University of Glasgow
- Investigators
- David J Stott, MBChB MD, Principal investigator, University of GlasgowJacobijn Gussekloo, MD, Principal investigator, Leiden University Medical CenterNicolas Rodondi, MD, Principal investigator, University of BernPatricia Kearney, MD, Principal investigator, University College CorkRudi JG Westendorp, MD, Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01660126
- Sponsor's protocol ID
- GN11GE272
- Other IDs
- 2011-004554-26
- Acronym
- TRUST
- Status last verified
- Mar 2017
- First submitted
- 6 Aug 2012
- Last updated
- 13 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
van der Spoel E, van Vliet NA, Poortvliet RKE, Du Puy RS, den Elzen WPJ, Quinn TJ, Stott DJ, Sattar N, Kearney PM, Blum MR, Alwan H, Rodondi N, Collet TH, Westendorp RGJ, Ballieux BE, Jukema JW, Dekkers OM, Gussekloo J, Mooijaart SP, van Heemst D. Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults. J Clin Endocrinol Metab. 2024 Feb 20;109(3):e1167-e1174. doi: 10.1210/clinem/dgad623.
PubMed 37862463Netzer S, Chocano-Bedoya P, Feller M, Janett-Pellegri C, Wildisen L, Buchi AE, Moutzouri E, Gonzalez Rodriguez E, Collet TH, Poortvliet RKE, Mc Carthy VJC, Aeberli D, Aujesky D, Westendorp R, Quinn TJ, Gussekloo J, Kearney PM, Mooijaart S, Bauer DC, Rodondi N. The effect of thyroid hormone therapy on muscle function, strength and mass in older adults with subclinical hypothyroidism-an ancillary study within two randomized placebo controlled trials. Age Ageing. 2023 Jan 8;52(1):afac326. doi: 10.1093/ageing/afac326.
PubMed 36721961Buchi AE, Feller M, Netzer S, Blum MR, Gonzalez Rodriguez E, Collet TH, Del Giovane C, van Heemst D, Quinn T, Kearney PM, Westendorp RGJ, Gussekloo J, Mooijaart SP, Hans D, Bauer DC, Rodondi N, Aeberli D. Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: A nested study within a randomized placebo controlled trial. Bone. 2022 Aug;161:116404. doi: 10.1016/j.bone.2022.116404. Epub 2022 Apr 2.
PubMed 35381390Du Puy RS, Poortvliet RKE, Mooijaart SP, Stott DJ, Quinn T, Sattar N, Westendorp RGJ, Kearney PM, McCarthy VJC, Byrne S, Rodondi N, Baretella O, Collet TH, van Heemst D, Dekkers OM, Jukema JW, Smit JWA, Gussekloo J, den Elzen WPJ. No Effect of Levothyroxine on Hemoglobin in Older Adults With Subclinical Hypothyroidism: Pooled Results From 2 Randomized Controlled Trials. J Clin Endocrinol Metab. 2022 May 17;107(6):e2339-e2347. doi: 10.1210/clinem/dgac106.
PubMed 35218666Zijlstra LE, Jukema JW, Westendorp RGJ, Du Puy RS, Poortvliet RKE, Kearney PM, O'Keeffe L, Dekkers OM, Blum MR, Rodondi N, Collet TH, Quinn TJ, Sattar N, Stott DJ, Trompet S, den Elzen WPJ, Gussekloo J, Mooijaart SP. Levothyroxine Treatment and Cardiovascular Outcomes in Older People With Subclinical Hypothyroidism: Pooled Individual Results of Two Randomised Controlled Trials. Front Endocrinol (Lausanne). 2021 May 20;12:674841. doi: 10.3389/fendo.2021.674841. eCollection 2021.
PubMed 34093444de Montmollin M, Feller M, Beglinger S, McConnachie A, Aujesky D, Collet TH, Ford I, Gussekloo J, Kearney PM, McCarthy VJC, Mooijaart S, Poortvliet RKE, Quinn T, Stott DJ, Watt T, Westendorp R, Rodondi N, Bauer DC. L-Thyroxine Therapy for Older Adults With Subclinical Hypothyroidism and Hypothyroid Symptoms: Secondary Analysis of a Randomized Trial. Ann Intern Med. 2020 Jun 2;172(11):709-716. doi: 10.7326/M19-3193. Epub 2020 May 5.
PubMed 32365355Gonzalez Rodriguez E, Stuber M, Del Giovane C, Feller M, Collet TH, Lowe AL, Blum MR, van Vliet NA, van Heemst D, Kearney PM, Gussekloo J, Mooijaart S, Westendorp RGJ, Stott DJ, Aeberli D, Bauer DC, Hans D, Rodondi N. Skeletal Effects of Levothyroxine for Subclinical Hypothyroidism in Older Adults: A TRUST Randomized Trial Nested Study. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz058. doi: 10.1210/clinem/dgz058.
PubMed 31702015Mooijaart SP, Du Puy RS, Stott DJ, Kearney PM, Rodondi N, Westendorp RGJ, den Elzen WPJ, Postmus I, Poortvliet RKE, van Heemst D, van Munster BC, Peeters RP, Ford I, Kean S, Messow CM, Blum MR, Collet TH, Watt T, Dekkers OM, Jukema JW, Smit JWA, Langhorne P, Gussekloo J. Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism. JAMA. 2019 Nov 26;322(20):1977-1986. doi: 10.1001/jama.2019.17274.
PubMed 31664429Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, Sattar N, Aubert CE, Aujesky D, Bauer DC, Baumgartner C, Blum MR, Browne JP, Byrne S, Collet TH, Dekkers OM, den Elzen WPJ, Du Puy RS, Ellis G, Feller M, Floriani C, Hendry K, Hurley C, Jukema JW, Kean S, Kelly M, Krebs D, Langhorne P, McCarthy G, McCarthy V, McConnachie A, McDade M, Messow M, O'Flynn A, O'Riordan D, Poortvliet RKE, Quinn TJ, Russell A, Sinnott C, Smit JWA, Van Dorland HA, Walsh KA, Walsh EK, Watt T, Wilson R, Gussekloo J; TRUST Study Group. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. N Engl J Med. 2017 Jun 29;376(26):2534-2544. doi: 10.1056/NEJMoa1603825. Epub 2017 Apr 3.
PubMed 28402245Stott DJ, Gussekloo J, Kearney PM, Rodondi N, Westendorp RG, Mooijaart S, Kean S, Quinn TJ, Sattar N, Hendry K, Du Puy R, Den Elzen WP, Poortvliet RK, Smit JW, Jukema JW, Dekkers OM, Blum M, Collet TH, McCarthy V, Hurley C, Byrne S, Browne J, Watt T, Bauer D, Ford I. Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST). BMC Endocr Disord. 2017 Feb 3;17(1):6. doi: 10.1186/s12902-017-0156-8.
PubMed 28158982
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-modal Effects of Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism; a Randomised Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT01660126
- Acronym / sponsor ID
- TRUST / GN11GE272
- Conditions
- Subclinical Hypothyroidism
- Keywords
- Aged, Cardiovascular disease, Levothyroxine, Randomised controlled trial, Quality of life, Subclinical hypothyroidism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 737 participants (actual)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow, University College Cork, University of Bern, Leiden University Medical Center
- Study start
- May 2014
- Primary completion
- 18 Nov 2016 (actual)
- Study completion
- 18 Nov 2016 (actual)
- First posted
- 8 Aug 2012 (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.
Subclinical hypothyroidism (SCH) is a common condition among older men and women. Although by definition SCH comprises biochemically mild thyroid hormone deficiency without overt symptoms, it is a possible contributor to multiple problems in older age. Thyroid hormone has effects on numerous physiological systems, including the vascular tree, heart, skeletal muscle and brain. Therefore, thyroxine substitution to overcome thyroid hormone deficiency has the potential to give multisystem benefits to older people with SCH.
Small studies have reported reduced atherosclerosis and improved heart function with thyroxine replacement, but no large clinical trials have been performed. Therefore the available evidence is limited, leading to major variations in guidelines and clinical practice, with uncertainty regarding the indications for screening and treatment. The investigators propose a multicentre randomised placebo controlled trial to assess the impact of thyroxine replacement in a minimum of 540 older adults (maximum 750) with persisting SCH (excluding those in whom it is a temporary phenomenon who are unlikely to benefit). The investigators will include older men and women with a wide age range and of varying health status. Outcomes include health related quality of life, muscle strength, executive cognitive function and cardiovascular events, with a minimum of 1 year of follow up. Blood and urine samples will be stored in a biobank, to allow future research on causes of ill health in older people with SCH.
The investigators have the support of patient advocacy groups and a consortium with the wide range of expertise and experience required to conduct large scale multicentre clinical trials. The proposal explores the multisystem and quality of life benefits to older people of a tailored approach to management of SCH.
This clinical trial should definitively clarify whether thyroxine treatment for SCH provides benefits that are relevant for patients. This trial will provide strong evidence with the potential to improve clinical practice, reduce health care costs and promote healthy ageing of older adults.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levothyroxine | Active comparator | Drug: LevothyroxineOral Levothyroxine, starting dose 25 or 50 micrograms increased to a maximum of 150 micrograms once daily. |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo |
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 (SCH).
- SCH is defined as elevated TSH levels (>=4.6, <=19.9 mU/L) and free thyroxine (fT4) in reference range measured on a minimum of two occasions at least 3 months apart.
Key exclusion criteria (10 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 |
|---|---|---|
| LevothyroxineAlso: ThyroxineThe 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. | Drug | Levothyroxine |
| Placebo | Drug | Placebo |
Primary outcome
Thyroid-specific quality of life - Hypothyroid symptoms and Fatigue symptoms (co-primary outcomes)
Time frame: Measured at baseline and 12 months
Change in Hypothyroid Symptoms and Fatigue scores (measured using the Thyroid-specific quality of life Patient Reported Outcome questionnaire - ThyPRO; Hypothyroid symptoms and Fatigue domains).
11 secondary outcomes
Health-related quality of life
Time frame: measured at baseline; 3 month; 12 month and final follow up (expected mean follow-up of 18 months).
Handgrip strength
Time frame: Measured at baseline; 12 months and final follow up (expected mean follow-up of 18 months).
Executive cognitive function
Time frame: Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Total mortality
Time frame: Up to final follow up (expected mean follow-up of 18 months).
Basic Activities of Daily Living
Time frame: Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Extended activities of daily living
Time frame: Measured at baseline and final follow-up (expected mean follow-up of 18 months).
Haemoglobin
Time frame: Measured at baseline and 1 year
Fatal and non-fatal cardiovascular events
Time frame: Expected mean follow-up of 18 months.
Generic thyroid specific quality of life
Time frame: Final follow-up
Thyroid-specific quality of life - Hypothyroid symptoms
Time frame: Measured at 6-8 weeks and at final review
Thyroid specific quality of life - Fatigue symptoms
Time frame: Measured at 6-8 weeks and at final review
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 13 Mar 2017.
- Derived from this study: PubMed 37862463van der Spoel E, van Vliet NA, Poortvliet RKE, Du Puy RS, den Elzen WPJ, Quinn TJ, Stott DJ, Sattar N, Kearney PM, Blum MR, Alwan H, Rodondi N, Collet TH, Westendorp RGJ, Ballieux BE, Jukema JW, Dekkers OM, Gussekloo J, Mooijaart SP, van Heemst D. Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults. J Clin Endocrinol Metab. 2024 Feb 20;109(3):e1167-e1174. doi: 10.1210/clinem/dgad623.
- Derived from this study: PubMed 36721961Netzer S, Chocano-Bedoya P, Feller M, Janett-Pellegri C, Wildisen L, Buchi AE, Moutzouri E, Gonzalez Rodriguez E, Collet TH, Poortvliet RKE, Mc Carthy VJC, Aeberli D, Aujesky D, Westendorp R, Quinn TJ, Gussekloo J, Kearney PM, Mooijaart S, Bauer DC, Rodondi N. The effect of thyroid hormone therapy on muscle function, strength and mass in older adults with subclinical hypothyroidism-an ancillary study within two randomized placebo controlled trials. Age Ageing. 2023 Jan 8;52(1):afac326. doi: 10.1093/ageing/afac326.
- Derived from this study: PubMed 35381390Buchi AE, Feller M, Netzer S, Blum MR, Gonzalez Rodriguez E, Collet TH, Del Giovane C, van Heemst D, Quinn T, Kearney PM, Westendorp RGJ, Gussekloo J, Mooijaart SP, Hans D, Bauer DC, Rodondi N, Aeberli D. Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: A nested study within a randomized placebo controlled trial. Bone. 2022 Aug;161:116404. doi: 10.1016/j.bone.2022.116404. Epub 2022 Apr 2.
- Derived from this study: PubMed 35218666Du Puy RS, Poortvliet RKE, Mooijaart SP, Stott DJ, Quinn T, Sattar N, Westendorp RGJ, Kearney PM, McCarthy VJC, Byrne S, Rodondi N, Baretella O, Collet TH, van Heemst D, Dekkers OM, Jukema JW, Smit JWA, Gussekloo J, den Elzen WPJ. No Effect of Levothyroxine on Hemoglobin in Older Adults With Subclinical Hypothyroidism: Pooled Results From 2 Randomized Controlled Trials. J Clin Endocrinol Metab. 2022 May 17;107(6):e2339-e2347. doi: 10.1210/clinem/dgac106.
- Derived from this study: PubMed 34093444Zijlstra LE, Jukema JW, Westendorp RGJ, Du Puy RS, Poortvliet RKE, Kearney PM, O'Keeffe L, Dekkers OM, Blum MR, Rodondi N, Collet TH, Quinn TJ, Sattar N, Stott DJ, Trompet S, den Elzen WPJ, Gussekloo J, Mooijaart SP. Levothyroxine Treatment and Cardiovascular Outcomes in Older People With Subclinical Hypothyroidism: Pooled Individual Results of Two Randomised Controlled Trials. Front Endocrinol (Lausanne). 2021 May 20;12:674841. doi: 10.3389/fendo.2021.674841. eCollection 2021.
- Derived from this study: PubMed 32365355de Montmollin M, Feller M, Beglinger S, McConnachie A, Aujesky D, Collet TH, Ford I, Gussekloo J, Kearney PM, McCarthy VJC, Mooijaart S, Poortvliet RKE, Quinn T, Stott DJ, Watt T, Westendorp R, Rodondi N, Bauer DC. L-Thyroxine Therapy for Older Adults With Subclinical Hypothyroidism and Hypothyroid Symptoms: Secondary Analysis of a Randomized Trial. Ann Intern Med. 2020 Jun 2;172(11):709-716. doi: 10.7326/M19-3193. Epub 2020 May 5.
- Derived from this study: PubMed 31702015Gonzalez Rodriguez E, Stuber M, Del Giovane C, Feller M, Collet TH, Lowe AL, Blum MR, van Vliet NA, van Heemst D, Kearney PM, Gussekloo J, Mooijaart S, Westendorp RGJ, Stott DJ, Aeberli D, Bauer DC, Hans D, Rodondi N. Skeletal Effects of Levothyroxine for Subclinical Hypothyroidism in Older Adults: A TRUST Randomized Trial Nested Study. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz058. doi: 10.1210/clinem/dgz058.
- Derived from this study: PubMed 31664429Mooijaart SP, Du Puy RS, Stott DJ, Kearney PM, Rodondi N, Westendorp RGJ, den Elzen WPJ, Postmus I, Poortvliet RKE, van Heemst D, van Munster BC, Peeters RP, Ford I, Kean S, Messow CM, Blum MR, Collet TH, Watt T, Dekkers OM, Jukema JW, Smit JWA, Langhorne P, Gussekloo J. Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism. JAMA. 2019 Nov 26;322(20):1977-1986. doi: 10.1001/jama.2019.17274.
- Derived from this study: PubMed 28402245Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, Sattar N, Aubert CE, Aujesky D, Bauer DC, Baumgartner C, Blum MR, Browne JP, Byrne S, Collet TH, Dekkers OM, den Elzen WPJ, Du Puy RS, Ellis G, Feller M, Floriani C, Hendry K, Hurley C, Jukema JW, Kean S, Kelly M, Krebs D, Langhorne P, McCarthy G, McCarthy V, McConnachie A, McDade M, Messow M, O'Flynn A, O'Riordan D, Poortvliet RKE, Quinn TJ, Russell A, Sinnott C, Smit JWA, Van Dorland HA, Walsh KA, Walsh EK, Watt T, Wilson R, Gussekloo J; TRUST Study Group. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. N Engl J Med. 2017 Jun 29;376(26):2534-2544. doi: 10.1056/NEJMoa1603825. Epub 2017 Apr 3.
- Derived from this study: PubMed 28158982Stott DJ, Gussekloo J, Kearney PM, Rodondi N, Westendorp RG, Mooijaart S, Kean S, Quinn TJ, Sattar N, Hendry K, Du Puy R, Den Elzen WP, Poortvliet RK, Smit JW, Jukema JW, Dekkers OM, Blum M, Collet TH, McCarthy V, Hurley C, Byrne S, Browne J, Watt T, Bauer D, Ford I. Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST). BMC Endocr Disord. 2017 Feb 3;17(1):6. doi: 10.1186/s12902-017-0156-8.
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Additive Efficacy of Physical Activity Program in Hypthyroidism Elder Females With Glaucoma and Fatty Liver Issues
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Thyroid Hormone Replacement After Coronary Artery Bypass Grafting for Patients With Subclinical Hypothyroidism
Subclinical Hypothyroidism
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.
David J Stott, MBChB MD principal investigator
University of Glasgow
Jacobijn Gussekloo, MD principal investigator
Leiden University Medical Center
Nicolas Rodondi, MD principal investigator
University of Bern
1 site in 1 country: 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, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.
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 10 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 13 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
Thyroid-specific quality of life - Hypothyroid symptoms and Fatigue symptoms (co-primary outcomes) (time frame: Measured at baseline and 12 months). 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 NCT01660126, which also lists 10 linked publications.
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 13 Mar 2017; AzTrials last refreshed its copy on 27 Oct 2026.