Pickering Gisèle, Pereira Bruno, Morel Véronique, Tiberghien Florence, Martin Elodie, Marcaillou Fabienne, Picard Pascale, Delage Noémie, de Montgazon Géraldine, Sorel Marc, Roux Delphine, Dubray Claude
Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, Laboratoire de Pharmacologie, Facultés de Médecine/Pharmacie, F-63000 Clermont-Ferrand, France; Inserm, U1107 Neuro-Dol, F-63001 Clermont-Ferrand, France.; CHU Clermont-Ferrand, Inserm CIC 1405, Centre de Pharmacologie Clinique, F-63003 Clermont-Ferrand, France..
CHU de Clermont-Ferrand, Délégation Recherche Clinique & Innovation - Villa annexe IFSI, 58 Rue Montalembert, F-63003 Clermont-Ferrand Cedex, France.
Contemp Clin Trials. 2014 Jul;38(2):314-20. doi: 10.1016/j.cct.2014.06.004. Epub 2014 Jun 16.
The N-methyl-D-aspartate receptor plays an important role in central sensitization of neuropathic pain and N-methyl-D-aspartate receptor antagonists, such as ketamine, memantine and dextromethorphan may be used for persistent pain. However, ketamine cannot be repeated too often because of its adverse events. A drug relay would be helpful in the outpatient to postpone or even cancel the next ketamine infusion. This clinical trial evaluates if memantine and/or dextromethorphan given as a relay to ketamine responders may maintain or induce a decrease of pain intensity and have a beneficial impact on cognition and quality of life. This trial is a multi-center, randomized, controlled and single-blind clinical study (NCT01602185). It includes 60 ketamine responder patients suffering from neuropathic pain. They are randomly allocated to memantine, dextromethorphan or placebo. After ketamine infusion, 60 patients received either memantine (maximal dose 20 mg/day), or dextromethorphan (maximal dose 90 mg/day), or placebo for 12 weeks. The primary endpoint is pain measured on a (0-10) Numeric Rating Scale 1 month after inclusion. Secondary outcomes include assessment of neuropathic pain, sleep, quality of life, anxiety/depression and cognitive function at 2 and 3 months. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α=0.05. This study will explore if oral memantine and/or dextromethorphan may be a beneficial relay in ketamine responders and may diminish ketamine infusion frequency. Preservation of cognitive function and quality of life is also a central issue that will be analyzed in these vulnerable patients.
N-甲基-D-天冬氨酸受体在神经性疼痛的中枢敏化中起重要作用，N-甲基-D-天冬氨酸受体拮抗剂，如氯胺酮、美金刚和右美沙芬可用于治疗持续性疼痛。然而，由于氯胺酮的不良事件，不能过于频繁地重复使用。药物接力有助于门诊患者推迟甚至取消下一次氯胺酮输注。本临床试验评估给予氯胺酮反应者的美金刚和/或右美沙芬作为接力用药是否可维持或降低疼痛强度，并对认知和生活质量产生有益影响。本试验是一项多中心、随机、对照和单盲临床研究（NCT01602185）。它纳入了60名患有神经性疼痛的氯胺酮反应者。他们被随机分配到美金刚组、右美沙芬组或安慰剂组。在氯胺酮输注后，60名患者接受美金刚（最大剂量20mg/天）、右美沙芬（最大剂量90mg/天）或安慰剂治疗12周。主要终点是入组1个月后用（0-10）数字评分量表测量的疼痛。次要结局包括在2个月和3个月时对神经性疼痛、睡眠、生活质量、焦虑/抑郁和认知功能的评估。使用混合模型进行数据分析，检验为双侧检验，I型错误设定为α=0.05。本研究将探讨口服美金刚和/或右美沙芬是否可能是氯胺酮反应者的有益接力用药，并可能减少氯胺酮输注频率。保护认知功能和生活质量也是这些易感患者中将进行分析的核心问题。
