title: Rationale and design of a multicenter randomized clinical trial with memantine and dextromethorphan in ketamine-responder patients.
abstract: 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.
authors.affiliation: 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.. Electronic address: gisele.pickering@udamail.fr.
authors.forename: Gisèle
authors.initials: G
authors.lastname: Pickering
authors.affiliation: CHU de Clermont-Ferrand, Délégation Recherche Clinique & Innovation - Villa annexe IFSI, 58 Rue Montalembert, F-63003 Clermont-Ferrand Cedex, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pereira
authors.affiliation: CHU Clermont-Ferrand, Inserm CIC 1405, Centre de Pharmacologie Clinique, F-63003 Clermont-Ferrand, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Morel
authors.affiliation: Centre d'Evaluation et de Traitement de la Douleur/Soins palliatifs, CHU Jean Minjoz, Besançon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Tiberghien
authors.affiliation: Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, Laboratoire de Pharmacologie, Facultés de Médecine/Pharmacie, F-63000 Clermont-Ferrand, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Martin
authors.affiliation: Centre d'Evaluation et de Traitement de la Douleur, CHU de Clermont-Ferrand, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Marcaillou
authors.affiliation: Centre d'Evaluation et de Traitement de la Douleur, CHU de Clermont-Ferrand, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Picard
authors.affiliation: Centre d'Evaluation et de Traitement de la Douleur, CHU de Clermont-Ferrand, France.
authors.forename: Noémie
authors.initials: N
authors.lastname: Delage
authors.affiliation: Centre d'Evaluation et de Traitement de la Douleur/Soins palliatifs, CH de La Rochelle, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: de Montgazon
authors.affiliation: Centre d'Evaluation et de Traitement de la Douleur/Soins palliatifs, Nemours, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sorel
authors.affiliation: CHU Clermont-Ferrand, Inserm CIC 1405, Centre de Pharmacologie Clinique, F-63003 Clermont-Ferrand, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Roux
authors.affiliation: 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.
authors.forename: Claude
authors.initials: C
authors.lastname: Dubray
mesh_terms: D003863:Depression / Q000453:epidemiology; D003915:Dextromethorphan / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use; D008559:Memantine / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D010147:Pain Measurement; D017060:Patient Satisfaction; D011788:Quality of Life; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012107:Research Design; D016037:Single-Blind Method
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D003915:Dextromethorphan; D008559:Memantine
keywords: Dextromethorphan; Ketamine; Memantine; NMDA receptor; Neuropathic pain; Quality of life