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Acipimox in Mitochondrial Myopathy (AIMM): study protocol for a randomised, double-blinded, placebo-controlled, adaptive design trial of the efficacy of acipimox in adult patients with mitochondrial myopathy

Lookup NU author(s): Dr Alaa AbouhajarORCiD, Dr Lisa AlcockORCiD, Dr Theophile Bigirumurame, Penny Bradley, Laura Brown, Ian Campbell, Dr Silvia Del DinORCiD, Julie Faitg, Gavin Falkous, Professor Grainne Gorman, Dr Rachel Lakey, Professor Bobby McFarlandORCiD, Jane Newman, Professor Lynn RochesterORCiD, Vicky Ryan, Hesther Smith, Dr Alison SteelORCiD, Dr Renae StefanettiORCiD, Dr Huizhong Su, Professor Robert Taylor, Dr Naomi Thomas, Dr Helen Tuppen, Dr Amy VincentORCiD, Dr Charlotte Warren, Gillian WatsonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022. The Author(s).BACKGROUND: Mitochondrial disease is a heterogenous group of rare, complex neurometabolic disorders. Despite their individual rarity, collectively mitochondrial diseases represent the most common cause of inherited metabolic disorders in the UK; they affect 1 in every 4300 individuals, up to 15,000 adults (and a similar number of children) in the UK. Mitochondrial disease manifests multisystem and isolated organ involvement, commonly affecting those tissues with high energy demands, such as skeletal muscle. Myopathy manifesting as fatigue, muscle weakness and exercise intolerance is common and debilitating in patients with mitochondrial disease. Currently, there are no effective licensed treatments and consequently, there is an urgent clinical need to find an effective drug therapy. AIM: To investigate the efficacy of 12-week treatment with acipimox on the adenosine triphosphate (ATP) content of skeletal muscle in patients with mitochondrial disease and myopathy. METHODS: AIMM is a single-centre, double blind, placebo-controlled, adaptive designed trial, evaluating the efficacy of 12 weeks' administration of acipimox on skeletal muscle ATP content in patients with mitochondrial myopathy. Eligible patients will receive the trial investigational medicinal product (IMP), either acipimox or matched placebo. Participants will also be prescribed low dose aspirin as a non-investigational medical product (nIMP) in order to protect the blinding of the treatment assignment. Eighty to 120 participants will be recruited as required, with an interim analysis for sample size re-estimation and futility assessment being undertaken once the primary outcome for 50 participants has been obtained. Randomisation will be on a 1:1 basis, stratified by Fatigue Impact Scale (FIS) (dichotomised as < 40, ≥ 40). Participants will take part in the trial for up to 20 weeks, from screening visits through to follow-up at 16 weeks post randomisation. The primary outcome of change in ATP content in skeletal muscle and secondary outcomes relating to quality of life, perceived fatigue, disease burden, limb function, balance and walking, skeletal muscle analysis and symptom-limited cardiopulmonary fitness (optional) will be assessed between baseline and 12 weeks. DISCUSSION: The AIMM trial will investigate the effect of acipimox on modulating muscle ATP content and whether it can be repurposed as a new treatment for mitochondrial disease with myopathy. TRIAL REGISTRATION: EudraCT2018-002721-29 . Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019,

Publication metadata

Author(s): Abouhajar A, Alcock L, Bigirumurame T, Bradley P, Brown L, Campbell I, Del Din S, Faitg J, Falkous G, Gorman GS, Lakey R, McFarland R, Newman J, Rochester L, Ryan V, Smith H, Steel A, Stefanetti RJ, Su H, Taylor RW, Thomas NJP, Tuppen H, Vincent AE, Warren C, Watson G

Publication type: Article

Publication status: Published

Journal: Trials

Year: 2022

Volume: 23

Issue: 1

Online publication date: 20/09/2022

Acceptance date: 13/07/2022

Date deposited: 03/10/2022

ISSN (electronic): 1745-6215

Publisher: BioMed Central Ltd.


DOI: 10.1186/s13063-022-06544-x

PubMed id: 36127727


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Funder referenceFunder name
MR/R006458/1Medical Research Council (MRC)