Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clinic (P.V., A.S.), Barcelona, Spain; Unitat de RM (Servei de Radiologia) (A.R., X.M.), Departamento de Neurología-Neuroinmunología, Centro de Esclerosis Múltiple de Cataluña (Cemcat), Hospital Vall d'Hebron, Barcelona, Spain; Hospital Clinico San Carlos (R.A., C.O.-G.), Madrid, Spain; NeuroCure Clinical Research Center and Department of Neurology (F.P.), Charité University Medicine Berlin, Berlin, Germany; Hospital de La Princesa (V.M.-L.), Madrid, Spain; Hospital Germans Trias i Pujol (C.R.), Badalona, Spain; Hospital Regional Universitario (IBIMA) (O.F.), Malaga, Spain; Hospital Puerta de Hierro (A.G.-M.), Madrid, Spain; Hospital Universitari Dr Josep Trueta (L.R.-T.), IDIBGI, Girona, Spain; Hospital La Fe (B.C.), Valencia, Spain; Hospital Xeral-Cies (D.M.), Vigo, Spain; Hospital del Mar (J.E.M.-R.), Barcelona, Spain; Deutsche Klinik für Diagnostik (E.L.), Wiesbaden, Germany; Hospital Universitario Santiago de Compostela (J.M.P.), Spain; Department of Neurology (S.G.M.), University of Munster, Germany; TrialFormSupport (X.N.), Barcelona, Spain; Advancell, Advanced In Vitro Cell Technologies, S.A (C.C.), Barcelona, Spain; and Neurotec Pharma S.L (M.P.), Barcelona, Spain.
Neurol Neuroimmunol Neuroinflamm. 2015 Sep 10;2(5):e147. doi: 10.1212/NXI.0000000000000147. eCollection 2015 Oct.
The aim of this study was to test the safety of diazoxide and to search for signs of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS).
In this multicenter, randomized, placebo-controlled, double-blind trial (treatment allocation was concealed), 102 patients with RRMS were randomized to receive a daily oral dose of diazoxide (0.3 and 4 mg/d) or placebo for 24 weeks (NCT01428726). The primary endpoint was the cumulative number of new T1 gadolinium-enhancing lesions per patient, recorded every 4 weeks from week 4 to week 24. Secondary endpoints included brain MRI variables such as the number of new/enlarging T2 lesions and the percentage brain volume change (PBVC); clinical variables such as the percentage of relapse-free patients, relapse rate, and change in the Expanded Disability Status Scale score; and safety and tolerability.
Diazoxide was well-tolerated and it produced no serious adverse events other than 1 case of Hashimoto disease. At the 2 doses tested, diazoxide did not improve the primary endpoint or the MRI and clinical variables related to the presence of new lesions or relapses. Patients treated with diazoxide showed reduced PBVC compared with the placebo group, although such changes could be confounded by the higher disease activity of the treated group and the vascular effects of diazoxide.
At the doses tested, oral diazoxide did not decrease the appearance of new lesions evident by MRI. The effects in slowing the progression of brain atrophy require further validation.
This study provides Class I evidence that for patients with RRMS, diazoxide (0.3 and 4 mg/d) does not significantly change the number of new MRI T1 gadolinium-enhancing lesions.
本研究旨在测试二氮嗪的安全性，并寻找其在复发性缓解型多发性硬化症（RRMS）患者中疗效的迹象。
在这项多中心、随机、安慰剂对照、双盲试验（治疗分配被隐藏）中，102 例 RRMS 患者被随机分为每日口服二氮嗪（0.3 和 4mg/d）或安慰剂组，治疗 24 周（NCT01428726）。主要终点是每位患者新出现的 T1 钆增强病变的累积数量，从第 4 周到第 24 周每 4 周记录一次。次要终点包括脑 MRI 变量，如新/扩大的 T2 病变数量和脑容量变化百分比（PBVC）；临床变量，如无复发患者的百分比、复发率和扩展残疾状态量表评分的变化；以及安全性和耐受性。
二氮嗪耐受性良好，除 1 例桥本氏病外，无其他严重不良事件。在测试的 2 个剂量下，二氮嗪均未改善主要终点或与新病变或复发相关的 MRI 和临床变量。与安慰剂组相比，接受二氮嗪治疗的患者 PBVC 降低，尽管这些变化可能受到治疗组疾病活动度较高和二氮嗪血管作用的影响。
在测试的剂量下，口服二氮嗪并未减少 MRI 显示的新病变的出现。减缓脑萎缩进展的效果需要进一步验证。
本研究提供了 I 级证据，表明对于 RRMS 患者，二氮嗪（0.3 和 4mg/d）不会显著改变新的 MRI T1 钆增强病变的数量。
