Novel Biomarkers and Skeletal Outcomes Associated With Subclinical Thyroid Dysfunction
Information source: University Hospital Inselspital, Berne
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Thyroid Dysfunction; Bone Density; Osteoporosis; Fractures, Bone
Intervention: Levothyroxine (Drug); Placebo (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: University Hospital Inselspital, Berne Official(s) and/or principal investigator(s): Nicolas Rodondi, MD MAS, Principal Investigator, Affiliation: Clinic for General Internal Medicine, Bern University Hospital Bern
Overall contact: Nicolas Rodondi, MD MAS, Phone: + 41 31 632 41 63, Email: nicolas.rodondi@insel.ch
Summary
Thyroid hormone is a key regulatory hormone for a range of physiological systems, including
the skeleton. Previous studies have suggested that subclinical thyroid dysfunction (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 between
thyroid hormone and bone loss. The aim of the study is to examine the relationship between
subclinical hypothyroidism and thyroid hormone replacement in regard to skeletal fragility,
bone mineral density (BMD), bone loss and metabolism, and the risk of fractures in elderly
participants. The listed parameters will be assessed by dual energy X ray absorptiometry
(DXA) and novel bone imaging techniques at baseline, at 1 year and 2 years of follow-up. The
study will be nested in the TRUST trial (clinicaltrials. gov ID: NCT01660126), and will make
use of its study infrastructure to determine bone biomarkers from biospecimens at baseline,
1 year and 2 years of follow-up from 120 Swiss participants with persistent subclinical
hypothyroidism randomized to either thyroxine or placebo in Bern and Lausanne.
Clinical Details
Official title: Novel Biomarkers and Skeletal Outcomes Associated With Subclinical Thyroid Dysfunction: a Prospective Evaluation and Impact of Treatment
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Change in bone mineral density (BMD)
Secondary outcome: Change in bone biomarkersbone mineral density (BMD)
Detailed description:
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 120 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, 1 year and 2 years of follow-up. In parallel, bone turnover markers in the blood
plasma will be measured at baseline, 1 year and 2 years of follow-up.
Eligibility
Minimum age: 65 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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)
Locations and Contacts
Nicolas Rodondi, MD MAS, Phone: + 41 31 632 41 63, Email: nicolas.rodondi@insel.ch
Clinic for General Internal Medicine, Bern University Hospital Bern, Bern 3010, Switzerland; Recruiting Nicolas Rodondi, MD MAS, Principal Investigator
Department of General Internal Medicine, Lausanne, Vaud 1011, Switzerland; Recruiting Nelly Pitteloud, MD, Phone: +41 (0)21 314 06 00, Email: nelly.pitteloud@chuv.ch Nelly Pitteloud, MD, Principal Investigator
Additional Information
Related publications: Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, Bremner A, Maisonneuve P, Sgarbi JA, Khaw KT, Vanderpump MP, Newman AB, Cornuz J, Franklyn JA, Westendorp RG, Vittinghoff E, Gussekloo J; Thyroid Studies Collaboration. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010 Sep 22;304(12):1365-74. doi: 10.1001/jama.2010.1361. Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, Bauer DC. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med. 2005 Nov 28;165(21):2460-6.
Starting date: January 2014
Last updated: July 6, 2015
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