Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST)

BMC Endocrine Disorders

Study Protocol

J. Wouter Jukema¹  Wendy P. J. Den Elzen²  Caroline Hurley³  John Browne⁴  Patricia M. Kearney⁴  Manuel Blum⁵  Torquil Watt⁶  Simon Mooijaart⁷  Olaf M. Dekkers⁷  Douglas Bauer⁸  Robert Du Puy⁹  Jacobijn Gussekloo⁹  Rosalinde K. E. Poortvliet⁹  Terence J. Quinn^1,10  Kirsty Hendry^1,10  David J. Stott^1,11  Naveed Sattar^1,12  Nicolas Rodondi^1,13  Rudi G. J. Westendorp^1,14  Jan W. A. Smit^1,15  Ian Ford^1,16  Sharon Kean^1,16  Vera McCarthy^1,17  Stephen Byrne^1,18  Tinh-Hai Collet^1,19 

[1] Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands;Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands;Department of Epidemiology and Public Health and Clinical Research Facility, University College Cork, Cork, Ireland;Department of Epidemiology and Public Health, University College Cork, Cork, Ireland;Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland;Department of Internal Medicine, Copenhagen University Hospital Herlev, Gentofte, Denmark;Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands;Department of Medicine, University of California, San Francisco, USA;Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands;Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK;Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK;Glasgow Royal Infirmary, Room 2.42, 2nd Floor New Lister Building, G31 2ER, Glasgow, UK;Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK;Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland;Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland;Leyden Academy on Vitality and Ageing, Leiden, Netherlands;Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark;Radboud University Medical Center, Nijmegen, The Netherlands;Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK;School of Nursing and Midwifery, University College Cork, Cork, Ireland;School of Pharmacy, University College Cork, Cork, Ireland;Service of Endocrinology Diabetes and Metabolism, University Hospital of Laussanne, Lausanne, Switzerland;

关键词: Subclinical hypothyroidism;    Elderly;    Randomised controlled trial;    Levothyroxine;    Quality of life;    Thyroid disease;   

DOI  :  10.1186/s12902-017-0156-8

 received in 2017-01-21, accepted in 2017-01-27,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundSubclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH.MethodsParticipants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects <50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients.Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture.DiscussionThis large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition.Trial registrationClinicaltrials.gov NCT01660126; registered 8th June 2012.

【 授权许可】

CC BY   
© The Author(s). 2017