Memantine for Enhanced Stroke Recovery

Summary

This will be a randomized double blind placebo-controlled pilot study using a repeated measures design in which participants with acute ischemic stroke and upper extremity weakness are randomized to either drug or placebo

Timeline

Start

2014-01

Primary completion

2026-12

Completion

2026-12

Publications

• Background Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation. 2013 Jan 1;127(1):143-52. doi: 10.1161/CIR.0b013e318282ab8f. No abstract available.
• Background Rathore SS, Hinn AR, Cooper LS, Tyroler HA, Rosamond WD. Characterization of incident stroke signs and symptoms: findings from the atherosclerosis risk in communities study. Stroke. 2002 Nov;33(11):2718-21. doi: 10.1161/01.str.0000035286.87503.31.
• Background Kalra L, Eade J. Role of stroke rehabilitation units in managing severe disability after stroke. Stroke. 1995 Nov;26(11):2031-4. doi: 10.1161/01.str.26.11.2031.
• Background Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, Guillon B, Moulin T, Marque P, Pariente J, Arnaud C, Loubinoux I. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb;10(2):123-30. doi: 10.1016/S1474-4422(10)70314-8. Epub 2011 Jan 7.
• Background Ziemann U, Ilic TV, Pauli C, Meintzschel F, Ruge D. Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex. J Neurosci. 2004 Feb 18;24(7):1666-72. doi: 10.1523/JNEUROSCI.5016-03.2004.
• Background Lipton SA. Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx. 2004 Jan;1(1):101-10. doi: 10.1602/neurorx.1.1.101.
• Background Chen HS, Lipton SA. Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism. J Physiol. 1997 Feb 15;499 ( Pt 1)(Pt 1):27-46. doi: 10.1113/jphysiol.1997.sp021909.
• Background Chen HS, Pellegrini JW, Aggarwal SK, Lei SZ, Warach S, Jensen FE, Lipton SA. Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J Neurosci. 1992 Nov;12(11):4427-36. doi: 10.1523/JNEUROSCI.12-11-04427.1992.
• Background Chen HS, Wang YF, Rayudu PV, Edgecomb P, Neill JC, Segal MM, Lipton SA, Jensen FE. Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience. 1998 Oct;86(4):1121-32. doi: 10.1016/s0306-4522(98)00163-8.
• Background Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist--a review of preclinical data. Neuropharmacology. 1999 Jun;38(6):735-67. doi: 10.1016/s0028-3908(99)00019-2.
• Background Kilic U, Yilmaz B, Reiter RJ, Yuksel A, Kilic E. Effects of memantine and melatonin on signal transduction pathways vascular leakage and brain injury after focal cerebral ischemia in mice. Neuroscience. 2013 May 1;237:268-76. doi: 10.1016/j.neuroscience.2013.01.059. Epub 2013 Feb 8.
• Background LUCAS DR, NEWHOUSE JP. The toxic effect of sodium L-glutamate on the inner layers of the retina. AMA Arch Ophthalmol. 1957 Aug;58(2):193-201. doi: 10.1001/archopht.1957.00940010205006. No abstract available.
• Background Leveille F, El Gaamouch F, Gouix E, Lecocq M, Lobner D, Nicole O, Buisson A. Neuronal viability is controlled by a functional relation between synaptic and extrasynaptic NMDA receptors. FASEB J. 2008 Dec;22(12):4258-71. doi: 10.1096/fj.08-107268. Epub 2008 Aug 18.
• Background Wenk GL, Zajaczkowski W, Danysz W. Neuroprotection of acetylcholinergic basal forebrain neurons by memantine and neurokinin B. Behav Brain Res. 1997 Feb;83(1-2):129-33. doi: 10.1016/s0166-4328(97)86056-1.
• Background Palmer GC. Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies. Curr Drug Targets. 2001 Sep;2(3):241-71. doi: 10.2174/1389450013348335.
• Background Babu CS, Ramanathan M. Pre-ischemic treatment with memantine reversed the neurochemical and behavioural parameters but not energy metabolites in middle cerebral artery occluded rats. Pharmacol Biochem Behav. 2009 May;92(3):424-32. doi: 10.1016/j.pbb.2009.01.010. Epub 2009 Jan 23.
• Background Cho GS, Lee JC, Ju C, Kim C, Kim WK. N-Methyl-D-aspartate receptor antagonists memantine and MK-801 attenuate the cerebral infarct accelerated by intracorpus callosum injection of lipopolysaccharides. Neurosci Lett. 2013 Mar 22;538:9-14. doi: 10.1016/j.neulet.2013.01.031. Epub 2013 Jan 30.
• Background Culmsee C, Junker V, Kremers W, Thal S, Plesnila N, Krieglstein J. Combination therapy in ischemic stroke: synergistic neuroprotective effects of memantine and clenbuterol. Stroke. 2004 May;35(5):1197-202. doi: 10.1161/01.STR.0000125855.17686.6d. Epub 2004 Apr 1.
• Background Lapchak PA. Memantine, an uncompetitive low affinity NMDA open-channel antagonist improves clinical rating scores in a multiple infarct embolic stroke model in rabbits. Brain Res. 2006 May 9;1088(1):141-7. doi: 10.1016/j.brainres.2006.02.093. Epub 2006 Apr 13.
• Background Montagne A, Hebert M, Jullienne A, Lesept F, Le Behot A, Louessard M, Gauberti M, Orset C, Ali C, Agin V, Maubert E, Vivien D. Memantine improves safety of thrombolysis for stroke. Stroke. 2012 Oct;43(10):2774-81. doi: 10.1161/STROKEAHA.112.669374. Epub 2012 Aug 9.
• Background Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):317-24. doi: 10.1001/jama.291.3.317.
• Background Emre M, Tsolaki M, Bonuccelli U, Destee A, Tolosa E, Kutzelnigg A, Ceballos-Baumann A, Zdravkovic S, Bladstrom A, Jones R; 11018 Study Investigators. Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 Oct;9(10):969-77. doi: 10.1016/S1474-4422(10)70194-0. Epub 2010 Aug 20.
• Background Iwamoto K, Ikeda K, Mizumura S, Tachiki K, Yanagihashi M, Iwasaki Y. Combined treatment of methylprednisolone pulse and memantine hydrochloride prompts recovery from neurological dysfunction and cerebral hypoperfusion in carbon monoxide poisoning: a case report. J Stroke Cerebrovasc Dis. 2014 Mar;23(3):592-5. doi: 10.1016/j.jstrokecerebrovasdis.2013.05.014. Epub 2013 Jun 19.
• Background Berthier ML, Green C, Lara JP, Higueras C, Barbancho MA, Davila G, Pulvermuller F. Memantine and constraint-induced aphasia therapy in chronic poststroke aphasia. Ann Neurol. 2009 May;65(5):577-85. doi: 10.1002/ana.21597.
• Background Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7(1):13-31.
• Background Duncan PW, Propst M, Nelson SG. Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident. Phys Ther. 1983 Oct;63(10):1606-10. doi: 10.1093/ptj/63.10.1606.
• Background Taub E, Miller NE, Novack TA, Cook EW 3rd, Fleming WC, Nepomuceno CS, Connell JS, Crago JE. Technique to improve chronic motor deficit after stroke. Arch Phys Med Rehabil. 1993 Apr;74(4):347-54.
• Background van der Lee JH, Beckerman H, Knol DL, de Vet HC, Bouter LM. Clinimetric properties of the motor activity log for the assessment of arm use in hemiparetic patients. Stroke. 2004 Jun;35(6):1410-4. doi: 10.1161/01.STR.0000126900.24964.7e. Epub 2004 Apr 15.
• Background Uswatte G, Taub E, Morris D, Light K, Thompson PA. The Motor Activity Log-28: assessing daily use of the hemiparetic arm after stroke. Neurology. 2006 Oct 10;67(7):1189-94. doi: 10.1212/01.wnl.0000238164.90657.c2.
• Background Collen FM, Wade DT, Bradshaw CM. Mobility after stroke: reliability of measures of impairment and disability. Int Disabil Stud. 1990 Jan-Mar;12(1):6-9. doi: 10.3109/03790799009166594.
• Background Duncan PW, Wallace D, Lai SM, Johnson D, Embretson S, Laster LJ. The stroke impact scale version 2.0. Evaluation of reliability, validity, and sensitivity to change. Stroke. 1999 Oct;30(10):2131-40. doi: 10.1161/01.str.30.10.2131.
• Background Kidd D, Stewart G, Baldry J, Johnson J, Rossiter D, Petruckevitch A, Thompson AJ. The Functional Independence Measure: a comparative validity and reliability study. Disabil Rehabil. 1995 Jan;17(1):10-4. doi: 10.3109/09638289509166622.

Drugs

Indications