Loading…

Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial

Summary Background Myostatin inhibits skeletal muscle growth. The humanised monoclonal antibody LY2495655 (LY) binds and neutralises myostatin. We aimed to test whether LY increases appendicular lean body mass (aLBM) and improves physical performance in older individuals who have had recent falls an...

Full description

Saved in:
Bibliographic Details
Published in:The lancet. Diabetes & endocrinology 2015-12, Vol.3 (12), p.948-957
Main Authors: Becker, Clemens, Prof, Lord, Stephen R, Prof, Studenski, Stephanie A, MD, Warden, Stuart J, PhD, Fielding, Roger A, Prof, Recknor, Christopher P, MD, Hochberg, Marc C, Prof, Ferrari, Serge L, Prof, Blain, Hubert, Prof, Binder, Ellen F, Prof, Rolland, Yves, Prof, Poiraudeau, Serge, Prof, Benson, Charles T, MD, Myers, Stephen L, MD, Hu, Leijun, PhD, Ahmad, Qasim I, MD, Pacuch, Kelli R, Gomez, Elisa V, MS, Benichou, Olivier, Dr
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Background Myostatin inhibits skeletal muscle growth. The humanised monoclonal antibody LY2495655 (LY) binds and neutralises myostatin. We aimed to test whether LY increases appendicular lean body mass (aLBM) and improves physical performance in older individuals who have had recent falls and low muscle strength and power. Methods In this proof-of-concept, randomised, placebo-controlled, double-blind, parallel, multicentre, phase 2 study, we recruited patients aged 75 years or older who had fallen in the past year from 21 investigator sites across Argentina, Australia, France, Germany, Sweden, and the USA. Eligible patients had low performance on hand grip strength and chair rise tests, tested with the procedure described by Guralnik and colleagues. Participants were stratified by country, age, hand grip strength, and performance on the chair rise test, and were randomly assigned (1:1) by a computer-generated random sequence to receive subcutaneous injections of placebo or 315 mg LY at weeks 0 (randomisation visit), 4, 8, 12, 16, and 20, followed by 16 weeks observation. The primary outcome was change in aLBM from baseline to 24 weeks. We measured physical performance as secondary outcomes (four-step stair climbing time, usual gait speed, and time to rise five times from a chair without arms, or with arms for participants unable to do it without arms) and exploratory outcomes (12-step stair climbing test, 6-min walking distance, fast gait speed, hand grip strength, and isometric leg extension strength). Efficacy analyses included all randomly assigned patients who received at least one dose and had a baseline and at least one subsequent measure. The primary analysis and all other tests of treatment effect (except physical performance tests) were done at a two-sided alpha level of 0·05. Tests of treatment effect on physical performance tests were done at a pre-specified two-sided alpha level of 0·1. This trial is registered with ClinicalTrials.gov , number NCT01604408. Findings Between June 19, 2012, and Dec 12, 2013, we screened 365 patients. 99 were randomly assigned to receive placebo and 102 to receive LY. Treatment was completed in 85 (86%) of patients given placebo and in 82 (80%) given LY. At 24 weeks, the least-squares mean change in aLBM was −0·123 kg (95% CI −0·287 to 0·040) in the placebo group and 0·303 kg (0·135 to 0·470) in the LY group, a difference of 0·43 kg (95% CI 0·192 to 0·660; p
ISSN:2213-8587
2213-8595
DOI:10.1016/S2213-8587(15)00298-3