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 (vol 23, 789, 2022)

被引：0

作者：

Abouhajar, Alaa ^{[1
]}

Alcock, Lisa ^{[2
]}

Bigirumurame, Theophile ^{[3
]}

Bradley, Penny ^{[4
]}

Brown, Laura

Campbell, Ian ^{[4
]}

Del Din, Silvia

Faitg, Julie ^{[5
]}

Falkous, Gavin ^{[5
]}

Gorman, Grainne S. ^{[5
]}

Lakey, Rachel ^{[1
]}

McFarland, Robert ^{[6
]}

Newman, Jane ^{[5
]}

Rochester, Lynn

Ryan, Vicky

Smith, Hesther

Steel, Alison ^{[1
]}

Stefanetti, Renae J. ^{[5
]}

Su, Huizhong ^{[5
]}

Taylor, Robert W. ^{[5
,6
]}

Thomas, Naomi J. P. ^{[5
,6
]}

Tuppen, Helen ^{[5
]}

Vincent, Amy E. ^{[5
]}

Warren, Charlotte ^{[5
]}

Watson, Gillian ^{[1
]}

机构：

[1] Newcastle Univ, Newcastle Clin Trials Unit, 1-4 Claremont Terrace, Newcastle Upon Tyne NE2 4AE, Tyne & Wear, England

[2] Newcastle Univ, Brain & Movement Res Grp, Clin Ageing Res Unit, Translat & Clin Res Inst, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England

[3] Newcastle Univ, Populat Hlth Sci Inst, Ridley 1 Bldg, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[4] Newcastle Tyne Hosp NHS Fdn Trust, Freeman Hosp, Pharm Directorate, Freeman Rd, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England

[5] Newcastle Univ, Wellcome Ctr Mitochondrial Res, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[6] Newcastle Tyne Hosp NHS Fdn Trust, NHS Highly Specialised Serv Rare Mitochondrial Di, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

来源：

TRIALS | 2022年 / 23卷 / 01期

基金：

英国惠康基金;

关键词：

Acipimox; Adenosine triphosphate; Mitochondria; Mitochondrial disease; Myopathy; Randomised controlled trial;

D O I：

10.1186/s13063-022-06814-8

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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, https://www.isrctn.com/search?q=aimm © 2022, The Author(s).

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