TY - JOUR
T1 - Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism
T2 - a randomised placebo controlled Trial (TRUST)
AU - Stott, David J.
AU - Gussekloo, Jacobijn
AU - Kearney, Patricia M.
AU - Rodondi, Nicolas
AU - Westendorp, Rudi G. J.
AU - Mooijaart, Simon P.
AU - Kean, Sharon
AU - Quinn, Terence J.
AU - Sattar, Naveed
AU - Hendry, Kirsty
AU - Du Puy, Robert
AU - Den Elzen, Wendy P. J.
AU - Poortvliet, Rosalinde K. E.
AU - Smit, Jan W. A.
AU - Jukema, J. Wouter
AU - Dekkers, Olaf M.
AU - Blum, Manuel
AU - Collet, Tinh-Hai
AU - McCarthy, Vera
AU - Hurley, Caroline
AU - Byrne, Stephen
AU - Browne, John
AU - Watt, Torquil
AU - Bauer, Douglas
AU - Ford, Ian
PY - 2017/2/3
Y1 - 2017/2/3
N2 - Background: Subclinical 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. Methods: Participants 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. Discussion: This 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 registration: Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.
AB - Background: Subclinical 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. Methods: Participants 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. Discussion: This 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 registration: Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.
KW - Aged
KW - Blood Banks
KW - Clinical Protocols
KW - Double-Blind Method
KW - Hormone Replacement Therapy
KW - Humans
KW - Hypothyroidism
KW - Patient Safety
KW - Thyroxine
KW - Journal Article
KW - Randomized Controlled Trial
U2 - 10.1186/s12902-017-0156-8
DO - 10.1186/s12902-017-0156-8
M3 - Journal article
C2 - 28158982
SN - 1472-6823
VL - 17
SP - 1
EP - 17
JO - B M C Endocrine Disorders
JF - B M C Endocrine Disorders
M1 - 6
ER -