Down Syndrome Memantine Follow-up Study

Summary

The purpose of this research study is to learn if the medication Memantine Hydrochloride (the study medication) can help adolescents and young adults with Down syndrome. Dr. Alberto Costa and his research team want to see if a 16-week treatment with this medication can improve the participant's ability to learn and remember things. In this study, memantine hydrochloride will be used. Thus, the researchers want to learn whether the study drug can help improve memory in young adults with Down syndrome. To test the effect of the study medicine, half of the people in the study will receive the study medicine and half will receive a placebo (an inactive substance). Memantine is an approved medication to treat memory and thinking problems in persons with Alzheimer disease. However, little is known about the effect of this medication in persons with Down syndrome and it has not been approved for use in persons with Down syndrome.

Timeline

Start

2014-10

Primary completion

2020-07-22

Completion

2020-07-22

Publications

• Background Abbeduto L, Pavetto M, Kesin E, Weissman MD, Karadottir S, O'Brien A, Cawthon S. The linguistic and cognitive profile of Down syndrome: evidence from a comparison with fragile X syndrome. Downs Syndr Res Pract. 2001 Oct;7(1):9-15. doi: 10.3104/reports.109.
• Background Bittles AH, Glasson EJ. Clinical, social, and ethical implications of changing life expectancy in Down syndrome. Dev Med Child Neurol. 2004 Apr;46(4):282-6. doi: 10.1017/s0012162204000441. No abstract available.
• Background Boada R, Hutaff-Lee C, Schrader A, Weitzenkamp D, Benke TA, Goldson EJ, Costa AC. Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial. Transl Psychiatry. 2012 Jul 17;2(7):e141. doi: 10.1038/tp.2012.66.
• Background Brock J, Jarrold C. Serial order reconstruction in Down syndrome: evidence for a selective deficit in verbal short-term memory. J Child Psychol Psychiatry. 2005 Mar;46(3):304-16. doi: 10.1111/j.1469-7610.2004.00352.x.
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• Background Chen KH, Reese EA, Kim HW, Rapoport SI, Rao JS. Disturbed neurotransmitter transporter expression in Alzheimer's disease brain. J Alzheimers Dis. 2011;26(4):755-766. doi: 10.3233/JAD-2011-110002.
• Background Chez MG, Burton Q, Dowling T, Chang M, Khanna P, Kramer C. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J Child Neurol. 2007 May;22(5):574-9. doi: 10.1177/0883073807302611.
• Background Costa AC, Scott-McKean JJ. Prospects for improving brain function in individuals with Down syndrome. CNS Drugs. 2013 Sep;27(9):679-702. doi: 10.1007/s40263-013-0089-3.
• Background Costa AC, Scott-McKean JJ, Stasko MR. Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test. Neuropsychopharmacology. 2008 Jun;33(7):1624-32. doi: 10.1038/sj.npp.1301535. Epub 2007 Aug 15.
• Background Danysz W, Parsons CG. Alzheimer's disease, beta-amyloid, glutamate, NMDA receptors and memantine--searching for the connections. Br J Pharmacol. 2012 Sep;167(2):324-52. doi: 10.1111/j.1476-5381.2012.02057.x.
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• Background Patterson D, Costa AC. Down syndrome and genetics - a case of linked histories. Nat Rev Genet. 2005 Feb;6(2):137-47. doi: 10.1038/nrg1525. No abstract available.
• Background Pennington BF, Moon J, Edgin J, Stedron J, Nadel L. The neuropsychology of Down syndrome: evidence for hippocampal dysfunction. Child Dev. 2003 Jan-Feb;74(1):75-93. doi: 10.1111/1467-8624.00522.
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• Background Rueda N, Llorens-Martin M, Florez J, Valdizan E, Banerjee P, Trejo JL, Martinez-Cue C. Memantine normalizes several phenotypic features in the Ts65Dn mouse model of Down syndrome. J Alzheimers Dis. 2010;21(1):277-90. doi: 10.3233/JAD-2010-100240.
• Background Sani G, Serra G, Kotzalidis GD, Romano S, Tamorri SM, Manfredi G, Caloro M, Telesforo CL, Caltagirone SS, Panaccione I, Simonetti A, Demontis F, Serra G, Girardi P. The role of memantine in the treatment of psychiatric disorders other than the dementias: a review of current preclinical and clinical evidence. CNS Drugs. 2012 Aug 1;26(8):663-90. doi: 10.2165/11634390-000000000-00000.
• Background Scott-McKean JJ, Costa AC. Exaggerated NMDA mediated LTD in a mouse model of Down syndrome and pharmacological rescuing by memantine. Learn Mem. 2011 Nov 18;18(12):774-8. doi: 10.1101/lm.024182.111. Print 2011 Dec.
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• Background Seung HK, Chapman R. Digit span in individuals with Down syndrome and in typically developing children: temporal aspects. J Speech Lang Hear Res. 2000 Jun;43(3):609-20. doi: 10.1044/jslhr.4303.609.
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• Background Tikhonravov D, Neuvonen T, Pertovaara A, Savioja K, Ruusuvirta T, Naatanen R, Carlson S. Dose-related effects of memantine on a mismatch negativity-like response in anesthetized rats. Neuroscience. 2010 Jun 2;167(4):1175-82. doi: 10.1016/j.neuroscience.2010.03.014. Epub 2010 Mar 15.
• Background Tilleux S, Hermans E. Neuroinflammation and regulation of glial glutamate uptake in neurological disorders. J Neurosci Res. 2007 Aug 1;85(10):2059-70. doi: 10.1002/jnr.21325.
• Background Turner S, Alborz A. Academic attainments of children with Down's syndrome: a longitudinal study. Br J Educ Psychol. 2003 Dec;73(Pt 4):563-83. doi: 10.1348/000709903322591244.
• Background Turner S, Alborz A, Gayle V. Predictors of academic attainments of young people with Down's syndrome. J Intellect Disabil Res. 2008 May;52(Pt 5):380-92. doi: 10.1111/j.1365-2788.2007.01038.x. Epub 2008 Jan 14.
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• Background Vicari S, Marotta L, Carlesimo GA. Verbal short-term memory in Down's syndrome: an articulatory loop deficit? J Intellect Disabil Res. 2004 Feb;48(Pt 2):80-92. doi: 10.1111/j.1365-2788.2004.00478.x.
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• Background Brandão IM, V. F, R. MR (2012) Prevalence of People with Down Syndrome in Brazil. In: Scientia Plena (www.scientiaplena.org.br).
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• Results Costa ACS, Brandao AC, Boada R, Barrionuevo VL, Taylor HG, Roth E, Stasko MR, Johnson MW, Assir FF, Roberto MP, Salmona P, Abreu-Silveira G, Bederman I, Prendergast E, Huls A, Abrishamcar S, Mustacchi Z, Scheidemantel T, Roizen NJ, Ruedrich S. Safety, efficacy, and tolerability of memantine for cognitive and adaptive outcome measures in adolescents and young adults with Down syndrome: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2022 Jan;21(1):31-41. doi: 10.1016/S1474-4422(21)00369-0.

Drugs

Indications