Novel Biomarkers and Skeletal Outcomes Associated With Subclinical Thyroid Dysfunction (TRUST BONE)
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| ClinicalTrials.gov Identifier: NCT02491008 |
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Recruitment Status :
Completed
First Posted : July 7, 2015
Last Update Posted : February 1, 2017
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Thyroid Dysfunction Bone Mineral Density Osteoporosis Fractures, Bone | Drug: Levothyroxine Drug: Placebo | Phase 4 |
Background
Thyroid hormone is a key regulatory hormone for other physiological systems, including the skeleton. Previous studies have suggested that SCTD may be associated with deleterious skeletal effects. However, controversy persists on the clinical relevance of SCTD as well as on optimal thresholds for treatment. Available data have substantial limitations: 1) limited prospective data are available to assess the associations between SCTD and non-cardiovascular outcomes, such as fractures 2) lack of data from large RCTs to investigate the pathophysiological mechanisms of associations.
Objective
To examine, within a large RCT of elderly participants with subclinical hypothyroidism (the TRUST trial), the impact of thyroxine therapy on the association between SCTD and skeletal fragility, bone mineral density (BMD), bone loss and metabolism, and the risk of fractures.
Methods
The existing trial infrastructure (TRUST thyroid trial-Euresearch FP7,clinicaltrials.gov ID: NCT01660126) will be utilized to collect biospecimens from the 145 Swiss participants with persistent subclinical hypothyroidism randomized to either thyroxine or placebo in Bern and in Lausanne. The assessment is performed by means of dual energy X ray absorptiometry (DXA) and peripheral quantitative computed tomography (pqCT) as a novel bone imaging technique at baseline, and at 1 year of follow-up. In parallel, bone turnover markers in the blood plasma will be measured at baseline and at 1 year of follow-up.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 145 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Novel Biomarkers and Skeletal Outcomes Associated With Subclinical Thyroid Dysfunction: a Prospective Evaluation and Impact of Treatment |
| Study Start Date : | January 2014 |
| Actual Primary Completion Date : | December 2016 |
| Actual Study Completion Date : | December 2016 |
| Arm | Intervention/treatment |
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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).
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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). |
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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. |
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. |
- Change in bone mineral density (BMD) [ Time Frame: baseline and one year follow up ]
- Change in bone biomarkers [ Time Frame: baseline and one year follow up ]
- Bone mineral density (BMD) [ Time Frame: 1 year follow up ]
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| Ages Eligible for Study: | 65 Years and older (Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Community-dwelling patients aged >= 65 years with subclinical hypothyroidism
- Written informed consent
Exclusion Criteria
- Subjects currently under levothyroxine or antithyroid drugs (amiodarone, lithium)
- Recent thyroid surgery or radio-iodine (within 12 months)
- Grade IV NYHA heart failure
- Prior clinical diagnosis of dementia
- Recent hospitalization 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02491008
| Switzerland | |
| Department of General Internal Medicine | |
| Lausanne, Vaud, Switzerland, 1011 | |
| Clinic for General Internal Medicine, Bern University Hospital Bern | |
| Bern, Switzerland, 3010 | |
| Principal Investigator: | Nicolas Rodondi, MD MAS | Clinic for General Internal Medicine, Bern University Hospital Bern |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | University Hospital Inselspital, Berne |
| ClinicalTrials.gov Identifier: | NCT02491008 |
| Other Study ID Numbers: |
162/11_3 SNF 320030_150025 ( Other Grant/Funding Number: SNF ) |
| First Posted: | July 7, 2015 Key Record Dates |
| Last Update Posted: | February 1, 2017 |
| Last Verified: | January 2017 |
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Thyroid Dysfunction Bone mineral density Osteoporosis Fractures, Bone Randomized Controlled Trial |
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Osteoporosis Thyroid Diseases Fractures, Bone Wounds and Injuries Endocrine System Diseases |
Bone Diseases, Metabolic Bone Diseases Musculoskeletal Diseases Metabolic Diseases |