Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over

Du Puy, R.S. et al. (2018) Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over. BMC Endocrine Disorders, 18, 67. (doi: 10.1186/s12902-018-0285-8) (PMID:30231866) (PMCID:PMC6146605)

Abstract

Background: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base. Methods: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure. Discussion: The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date.

• Item Type: Articles
• Additional Information: The IEMO 80-plus thyroid trial has been peer reviewed and approved for funding under the ZonMw programme Evidence-based Medicine in Old Age, ZonMW programme number: 627001001. The Swiss part of the trial was supported by grants from the Swiss National Science Foundation to Dr. Rodondi (SNF 320030–150025 and 320030–172676). The TRUST study was supported by a research grant from the European Union FP7-HEALTH-2011 programme - Investigator-driven clinical trials for therapeutic interventions in elderly populations. Grant agreement number 278148. Study medication was supplied free of charge by Merck KGaA.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kean, Ms Sharon and Messow, Dr Martina and Stott J, Professor David and Ford, Professor Ian
• Authors: Du Puy, R.S., Postmus, I., Stott, D.J., Blum, M.R., Poortvliet, R.K.E., Den Elzen, W.P.J., Peeters, R.P., van Munster, B.C., Wolffenbuttel, B.H.R., Westendorp, R.G.J., Kearney, P.M., Ford, I., Kean, S., Messow, C.M., Watt, T., Jukema, J.W., Dekkers, O.M., Smit, J.W.A., Rodondi, N., Gussekloo, J., and Mooijaart, S.P.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: BMC Endocrine Disorders
• Publisher: BioMed Central Ltd.
• ISSN: 1472-6823
• ISSN (Online): 1472-6823
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in BMC Endocrine Disorders 18:67
• Publisher Policy: Reproduced under a Creative Commons License