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Abstract

Introduction: Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening.Methods and analysis: A multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population.

Item Type:	Article
Authors/Creators:	Mackintosh, JA and Pietsch, M and Lutzky, V and Enever, D and Bancroft, S and Apte, SH and Tan, M and Yerkovich, ST and Dickinson, JL and Pickett, HA and Selvadurai, H and Grainge, C and Goh, NS and Hopkins, P and Glaspole, I and Reynolds, PN and Wrobel, J and Jaffe, A and Corte, TJ and Chambers, DC
Keywords:	pulmonary fibrosis, familial, inherited predisposition
Journal or Publication Title:	BMJ Open Respiratory Research
Publisher:	BMJ Publishing Group Ltd & British Thoracic Society
ISSN:	2052-4439
DOI / ID Number:	https://doi.org/10.1136/bmjresp-2021-001127
Copyright Information:	© Author(s) (or their employer(s)) 2021. Re-use permitted under the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.commercial re-use. See rights and permissions. Published by BMJ
Related URLs:	Google Scholar: Dickinson, JL UTAS Profile: Dickinson, JL
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