PDF(Pubmed)
Abstract：
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.
OBJECTIVE: 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.
CONCLUSIONS: 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.
BACKGROUND: EudraCT2018-002721-29 . Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019, https://www.isrctn.com/search?q=aimm.
OBJECTIVE: 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.
CONCLUSIONS: 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.
BACKGROUND: EudraCT2018-002721-29 . Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019, https://www.isrctn.com/search?q=aimm.
摘要：
背景：线粒体病是一种罕见的异质性疾病，复杂的神经代谢紊乱。尽管他们个人罕见，线粒体疾病是英国遗传性代谢紊乱的最常见原因；它们影响每4300个人中的1人，在英国，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和孤立的器官受累，通常影响那些需要高能量的组织，比如骨骼肌。肌病表现为疲劳，肌肉无力和运动不耐受在线粒体疾病患者中很常见，并且会使人衰弱。目前,没有有效的许可治疗，因此，临床上迫切需要找到一种有效的药物治疗方法。
目的：观察阿昔莫司治疗12周对线粒体疾病和肌病患者骨骼肌三磷酸腺苷（ATP）含量的影响。
方法：AIMM是单中心，双盲,安慰剂对照,适应性设计试验，评估12周服用阿昔莫司对线粒体肌病患者骨骼肌ATP含量的疗效。符合条件的患者将获得试验研究药品（IMP），阿昔莫司或匹配的安慰剂。参与者还将被处方低剂量阿司匹林作为非研究性医疗产品（nIMP），以保护治疗分配的致盲。将根据需要招募80至120名参与者,一旦获得50名参与者的主要结局，就会进行样本量重新估计和无效评估的中期分析。随机化将以1:1为基础，按疲劳冲击量表(FIS)分层(二分为<40，≥40)。参与者将参加长达20周的试验，从筛选访问到随机分组后16周的随访。骨骼肌中ATP含量变化的主要结果和与生活质量相关的次要结果，感知疲劳，疾病负担,肢体功能,平衡和行走，将在基线和12周之间评估骨骼肌分析和症状受限的心肺适合度(可选).
结论：AIMM试验将研究阿昔莫司对调节肌肉ATP含量的作用，以及它是否可以作为线粒体疾病伴肌病的新疗法。
背景：EudraCT2018-002721-29。于2018年12月24日注册，ISRCTN12895613。2019年1月3日注册，https://www。isrctn.com/search?q=aimm.
目的：观察阿昔莫司治疗12周对线粒体疾病和肌病患者骨骼肌三磷酸腺苷（ATP）含量的影响。
方法：AIMM是单中心，双盲,安慰剂对照,适应性设计试验，评估12周服用阿昔莫司对线粒体肌病患者骨骼肌ATP含量的疗效。符合条件的患者将获得试验研究药品（IMP），阿昔莫司或匹配的安慰剂。参与者还将被处方低剂量阿司匹林作为非研究性医疗产品（nIMP），以保护治疗分配的致盲。将根据需要招募80至120名参与者,一旦获得50名参与者的主要结局，就会进行样本量重新估计和无效评估的中期分析。随机化将以1:1为基础，按疲劳冲击量表(FIS)分层(二分为<40，≥40)。参与者将参加长达20周的试验，从筛选访问到随机分组后16周的随访。骨骼肌中ATP含量变化的主要结果和与生活质量相关的次要结果，感知疲劳，疾病负担,肢体功能,平衡和行走，将在基线和12周之间评估骨骼肌分析和症状受限的心肺适合度(可选).
结论：AIMM试验将研究阿昔莫司对调节肌肉ATP含量的作用，以及它是否可以作为线粒体疾病伴肌病的新疗法。
背景：EudraCT2018-002721-29。于2018年12月24日注册，ISRCTN12895613。2019年1月3日注册，https://www。isrctn.com/search?q=aimm.
