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.
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.
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线粒体疾病是一组罕见的复杂的神经代谢疾病。尽管线粒体疾病个别罕见，但在英国，线粒体疾病是遗传性代谢紊乱的最常见原因；在英国，每4300人中就有1人受到影响，多达15,000名成年人(以及类似数量的儿童)。线粒体疾病表现为多系统、孤立器官受累，常累及骨骼肌等能量需求较高的组织。表现为疲劳、肌肉无力和运动不耐受的肌病在线粒体疾病患者中很常见，并使人虚弱。目前，没有有效的许可治疗方法，因此，临床上迫切需要找到有效的药物治疗方法。目的：探讨阿昔莫司治疗12周对线粒体疾病合并肌病患者骨骼肌三磷酸腺苷(ATP)含量的影响。AIMM是一项单中心、双盲、安慰剂对照、适应性设计的试验，评估12周阿昔莫司对线粒体肌病患者骨骼肌ATP含量的影响。符合条件的患者将接受试验研究药物产品(IMP)，阿昔莫司或匹配的安慰剂。参与者还将被开出低剂量的阿司匹林作为非研究医疗产品(NIMP)，以保护治疗任务的失明。将根据需要招募80至120名参与者，一旦获得50名参与者的初步结果，将对样本量重新估计和有效性评估进行中期分析。随机化将在1：1的基础上，按疲劳影响等级(≥40)进行分层。参与者将参加长达20周的试验，从筛选就诊到随机化后16周的随访。将在基线至12周期间评估骨骼肌中ATP含量变化的主要结果以及与生活质量、感知疲劳、疾病负担、肢体功能、平衡和行走、骨骼肌分析和症状受限的心肺健康(可选)有关的次要结果。AIMM试验将调查阿昔莫司对调节肌肉ATP含量的作用，以及它是否可以被重新用于治疗伴有肌病的线粒体疾病的新疗法。EudraCT2018-002721-29。注册于2018年12月24日，ISRCTN 12895613。Https://www.isrctn.com/search?q=aimm于2019年1月3日注册，在线版本包含补充材料，可在10.1186/s13063-022-06544-x上查阅。
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. 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. 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. 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. EudraCT2018-002721-29. Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019, https://www.isrctn.com/search?q=aimm The online version contains supplementary material available at 10.1186/s13063-022-06544-x.
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与成年线粒体疾病有关的核和线粒体DNA突变的患病率。
影响因子：
11.2
作者：
Gorman GS;Schaefer AM;Ng Y;Gomez N;Blakely EL;Alston CL;Feeney C;Horvath R;Yu-Wai-Man P;Chinnery PF;Taylor RW;Turnbull DM;McFarland R
通讯作者：
McFarland R
影响因子：
7.7
作者：
van de Weijer T;Phielix E;Bilet L;Williams EG;Ropelle ER;Bierwagen A;Livingstone R;Nowotny P;Sparks LM;Paglialunga S;Szendroedi J;Havekes B;Moullan N;Pirinen E;Hwang JH;Schrauwen-Hinderling VB;Hesselink MK;Auwerx J;Roden M;Schrauwen P
通讯作者：
Schrauwen P
影响因子：
10.6
作者：
Duchen, Michael R.
通讯作者：
Duchen, Michael R.
影响因子：
2
作者：
Gould, AL
通讯作者：
Gould, AL
影响因子：
2.5
作者：
Sully, Benjamin G. O.;Julious, Steven A.;Nicholl, Jon
通讯作者：
Nicholl, Jon