Acipimox 250mg capsules

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.

Abstract licence: CC BY 4.0

Rationale: Drug-induced liver injury (DILI) is a prevalent and critical etiology of acute liver failure that often results in substantial health complications and mortality. Acipimox is a pharmacological agent used for lipid reduction, whereas telmisartan is prescribed for hypertension management. We report a case of severe DILI attributed to the concomitant use of acipimox and telmisartan, and we analyze the potential underlying mechanisms. Patient concerns: A 58-year-old female was admitted to our hospital with anorexia lasting >6 months. The patient had a history of taking oral antihypertensive medication (telmisartan) and lipid-lowering medications (atorvastatin and acipimox), with suspected DILI. Diagnoses: The patient was diagnosed with DILI. Interventions: After discontinuation of the suspected hepatotoxic agents telmisartan and acipimox, the patient received anti-inflammatory therapy with glucocorticoids along with hepatoprotective treatment including glutathione, S-adenosylmethionine, and bicyclol. Outcomes: The patient’s liver function has substantially normalized. Lessons: This study is the first to highlight a significant case of severe liver injury resulting from concurrent administration of acipimox and telmisartan, which is potentially influenced by factors such as age, sex, drug interactions, and genetic polymorphisms. This study aimed to emphasize the significance of implementing precise and individualized treatment strategies for managing drug combinations for patients with multiple comorbidities.

Abstract licence: CC BY 4.0