Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia

Summary

The primary objective of the study is to determine whether memantine is effective in slowing the rate of behavioral decline in frontotemporal dementia. The secondary objective of the study is to assess the safety and tolerability of long-term treatment with memantine in patients with frontotemporal dementia (FTD) or semantic dementia (SD). To determine whether memantine is effective in slowing the rate of cognitive decline in frontotemporal dementia. To evaluate whether memantine delays or decreases the emergence of parkinsonism in frontotemporal dementia. The tertiary objective of the study is to determine whether treatment with memantine affects changes in weight

Timeline

Start

2007-10

Primary completion

2012-12

Completion

2012-12

Outcome

Missed primary endpoint

paper Memantine treatment had no effect on either the NPI (mean difference 2·2, 95% CI PMID 23290598 ↗

paper p=0·47) or CGIC (mean difference 0·0, -0·4 to 0·4, p=0·90) PMID 23290598 ↗

Publications

• Background Amadoro G, Ciotti MT, Costanzi M, Cestari V, Calissano P, Canu N. NMDA receptor mediates tau-induced neurotoxicity by calpain and ERK/MAPK activation. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2892-7. doi: 10.1073/pnas.0511065103. Epub 2006 Feb 13.
• Background Boxer AL, Miller BL. Clinical features of frontotemporal dementia. Alzheimer Dis Assoc Disord. 2005 Oct-Dec;19 Suppl 1:S3-6. doi: 10.1097/01.wad.0000183086.99691.91.
• Background Boxer AL, Trojanowski JQ, Lee VY-M, Miller BL (2005) Frontotemporal Lobar Degeneration. In: Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics (Beal MF, Lang AE, Ludolph AC, eds), pp 481 - 493. Cambridge, UK: Cambridge University Press.
• Background Cullum CM, Saine K, Chan LD, Martin-Cook K, Gray KF, Weiner MF. Performance-Based instrument to assess functional capacity in dementia: The Texas Functional Living Scale. Neuropsychiatry Neuropsychol Behav Neurol. 2001 Apr-Jun;14(2):103-8.
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• Background Forman MS, Farmer J, Johnson JK, Clark CM, Arnold SE, Coslett HB, Chatterjee A, Hurtig HI, Karlawish JH, Rosen HJ, Van Deerlin V, Lee VM, Miller BL, Trojanowski JQ, Grossman M. Frontotemporal dementia: clinicopathological correlations. Ann Neurol. 2006 Jun;59(6):952-62. doi: 10.1002/ana.20873.
• Background Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology. 2006 Jan 10;66(1):17-22. doi: 10.1212/01.wnl.0000191304.55196.4d.
• Background Josephs KA, Petersen RC, Knopman DS, Boeve BF, Whitwell JL, Duffy JR, Parisi JE, Dickson DW. Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP. Neurology. 2006 Jan 10;66(1):41-8. doi: 10.1212/01.wnl.0000191307.69661.c3.
• Background Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, Hauser MF, Witte RJ, Boeve BF, Knopman DS, Dickson DW, Jack CR Jr, Petersen RC. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain. 2006 Jun;129(Pt 6):1385-98. doi: 10.1093/brain/awl078. Epub 2006 Apr 13.
• Background Kertesz A, Davidson W, Fox H. Frontal behavioral inventory: diagnostic criteria for frontal lobe dementia. Can J Neurol Sci. 1997 Feb;24(1):29-36. doi: 10.1017/s0317167100021053.
• Background Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal dementia. Brain. 2005 Sep;128(Pt 9):1996-2005. doi: 10.1093/brain/awh598. Epub 2005 Jul 20.
• Background Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov. 2006 Feb;5(2):160-70. doi: 10.1038/nrd1958.
• Background Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994 Mar 3;330(9):613-22. doi: 10.1056/NEJM199403033300907. No abstract available.
• Background Mendez MF, Shapira JS, McMurtray A, Licht E. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry. 2007 Jan;15(1):84-7. doi: 10.1097/01.JGP.0000231744.69631.33.
• Background Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging. 2004;21(14):931-7. doi: 10.2165/00002512-200421140-00003.
• Background Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993 Nov;43(11):2412-4. doi: 10.1212/wnl.43.11.2412-a. No abstract available.
• Background Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998 Dec;51(6):1546-54. doi: 10.1212/wnl.51.6.1546.
• Background Orgogozo JM, Rigaud AS, Stoffler A, Mobius HJ, Forette F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke. 2002 Jul;33(7):1834-9. doi: 10.1161/01.str.0000020094.08790.49.
• Background Pijnenburg YA, Sampson EL, Harvey RJ, Fox NC, Rossor MN. Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration. Int J Geriatr Psychiatry. 2003 Jan;18(1):67-72. doi: 10.1002/gps.774.
• Background Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ; Memantine Study Group. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14):1333-41. doi: 10.1056/NEJMoa013128.
• Background Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984 Nov;141(11):1356-64. doi: 10.1176/ajp.141.11.1356.
• Background Royall DR, Mahurin RK, Gray KF. Bedside assessment of executive cognitive impairment: the executive interview. J Am Geriatr Soc. 1992 Dec;40(12):1221-6. doi: 10.1111/j.1532-5415.1992.tb03646.x.
• 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 Wilcock G, Mobius HJ, Stoffler A; MMM 500 group. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol. 2002 Nov;17(6):297-305. doi: 10.1097/00004850-200211000-00005.
• Background Winblad B, Poritis N. Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry. 1999 Feb;14(2):135-46. doi: 10.1002/(sici)1099-1166(199902)14:23.0.co;2-0.
• Results Boxer AL, Knopman DS, Kaufer DI, Grossman M, Onyike C, Graf-Radford N, Mendez M, Kerwin D, Lerner A, Wu CK, Koestler M, Shapira J, Sullivan K, Klepac K, Lipowski K, Ullah J, Fields S, Kramer JH, Merrilees J, Neuhaus J, Mesulam MM, Miller BL. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2013 Feb;12(2):149-56. doi: 10.1016/S1474-4422(12)70320-4. Epub 2013 Jan 2.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Memantine	Unknown	10 mg	Oral

Indications