在早期帕金森病中使用lixisenatide的试验
Wassilios G Meissner1, Philippe Remy1, Caroline Giordana1
1From the French Clinical Research Network (F-CRIN) for Parkinson's Disease and Movement Disorders (NS-Park-F-CRIN) (W.G.M., P.R., C. Giordana, D.M., P. Derkinderen, J.-L.H., M.A., I.B., T.B., C.B.-C., N.C., O.C., J.-C.C., P. Damier, E.D., D.D., S.D., M.F., V.F., A.F.-S., S.F.-K., S.G., C.H., L.H., P.K., B.L., R.L., L.-L.M., A.M., C.M., F.O.-M., H.S., C. Thiriez, M.T., O.R.), Centre d'Investigation Clinique (CIC) 1436 and the Departments of Clinical Pharmacology and Neurosciences, Centre Expert Parkinson, University Hospital of Toulouse, INSERM, University of Toulouse 3 (C.B.-C., H.C., M.F., F.O.-M., C. Thalamas, O.R.), and CIC 1436, INSERM (E.D., A.S.), Toulouse, Service de Neurologie des Maladies Neurodégénératives, Centre Expert Parkinson, Institut des Maladies Neurodégénératives (IMN) Clinique (W.G.M., T.B., A.F.-S., B.L.), and Service d'Information Médicale, Unité de Soutien Méthodologique à la Recherche (USMR) (A.G., C. Germain, A.B.), Centre Hospitalier Universitaire (CHU) Bordeaux, Unité Mixte de Recherche (UMR) 5293, Université de Bordeaux, Centre National de la Recherche Scientifique (CNRS), IMN, Unité Mixte de Recherche (UMR) 5293 (W.G.M., T.B., A.F.-S.), and the European Clinical Trials Platform and Development-F-CRIN, CIC-Clinical Epidemiology Unit 1401, University of Bordeaux, INSERM, Institut Bergonié, CHU Bordeaux (A.G., C. Germain, A.B.), Bordeaux, the Department of Neurology, Centre Expert Parkinson, Equipe 01-Neuropsychologie Interventionnelle L'Institut Mondor de Recherches Biomédicales, CHU Henri Mondor, INSERM et Faculté de Santé, Université Paris-Est Créteil, Créteil (P.R., H.S.), the Department of Neurology, Centre Expert Parkinson, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice (C. Giordana, V.F., C.M.), the Department of Neurology, Centre Expert Parkinson, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, UMR 1239, Rouen University Hospital, University of Rouen, INSERM, Mont-Saint-Aignan (D.M.), and the Department of Neurology, Centre Expert Parkinson, Rouen University Hospital and University of Rouen (C.H., R.L.), Rouen, the Department of Neurology, Centre Expert Parkinson, CIC 1413, CHU Nantes, INSERM, Nantes (P. Derkinderen, P. Damier), Service de Neurologie, Centre Expert Parkinson, CIC 1402, CHU Limoges, CHU Poitiers INSERM, Limoges (J.-L.H., I.B., O.C.), the Department of Neurology, Centre Expert Parkinson, Strasbourg University Hospital, and Strasbourg Federation of Translational Medicine, Strasbourg University, Strasbourg (M.A.), the Institute of Genetics and Cellular and Molecular Biology, INSERM Unité 964, CNRS-UMR 7104, University of Strasbourg, Illkirch-Graffenstaden (M.A.), the Department of Medical Pharmacology INSERM Unité 1172, Lille Neurosciences and Cognition, Centre Hospitalier Régional Universitaire, University of Lille, Lille (N.C., D.D.), the Department of Neurology, CIC Neurosciences, Sorbonne Université, Paris Brain Institute, Assistance Publique-Hôpitaux de Paris, INSERM, CNRS, Pitié-Salpêtrière Hospital, Paris (J.-C.C., L.-L.M.), the Department of Neurology, Centre Expert Parkinson, CIC 1414, CHU Pontchaillou de Rennes, INSERM, Rennes (S.D.), the Department of Neurology, Centre Expert Parkinson, CHU de Nancy, Hôpital Central, Nancy (S.F.-K., L.H.), the Department of Neurology, Centre Expert Parkinson, University Hospital La Timone, Marseille (S.G.), the Department of Neurology, Centre Expert Parkinson, University Hospital of Amiens, Amiens (P.K., M.T.), the Department of Neurology, CHU Clermont-Ferrand, Université Clermont-Auvergne, CNRS, Image Guided Clinical Neuroscience and Connectomics, Institut Pascal, Clermont-Ferrand (A.M.), the Department of Nutrition-Diabetology, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac (V.R.), and the Department of Neurology, Centre Expert Parkinson, CHU de Caen, Caen (C. Thiriez) - all in France; the Department of Medicine, University of Otago, Christchurch, and the New Zealand Brain Research Institute - both in Christchurch, New Zealand (W.G.M.); Specialized Rehabilitation Hospital, Capital Health, Abu Dhabi, United Arab Emirates (P.K.); and Cure Parkinson's, London (S.R.W.S., R.K.W.).
在2期试验中,糖尿病药物lixisenatide在早期帕金森病患者中显示出减缓运动残疾进展的潜力. 需要进一步的研究来确认有效性和安全性,尽管有胃肠道副作用.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 临床试验 临床试验
背景情况:
- 利克西塞纳提德是一种类似葡萄糖类-1受体激动剂,用于糖尿病治疗.
- 之前在小鼠模型上的研究表明,lixisenatide在帕金森病中具有神经保护性.
研究的目的:
- 评估lixisenatide在缓解早期帕金森病运动残疾进展方面的疗效.
- 评估lixisenatide在这个患者群体中的安全性和耐受性.
主要方法:
- 一个第二阶段,双盲,随机,安慰剂对照试验,涉及156名患有早期帕金森病的参与者.
- 参与者每天接受皮下lixisenatide或安慰剂12个月,随后是2个月的洗期.
- 主要终点是12个月后运动障碍学会统一帕金森病评分表 (MDS-UPDRS) 第三部分分数的变化.
主要成果:
- 与安慰剂相比,lixisenatide治疗导致运动残疾进展的统计学上显著差异 (在12个月后在MDS-UPDRS部分III上变化为-0.04比3.04分).
- 在14个月后,在洗期后,lixisenatide组的运动得分仍然有所改善.
- 胃肠道副作用,包括恶心 (46%) 和吐 (13%),在lixisenatide组中更频繁地报告.
结论:
- 利克西纳提德在12个月的时间内显示出降低早期帕金森病中运动残疾进展的潜力.
- 观察到的胃肠道副作用需要仔细考虑.
- 需要进行更大规模,更长期的试验,以确定lixisenatide在帕金森病治疗中的有效性和安全性.
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