Down Syndrome Memantine Follow-up Study

NCT02304302 | Completed Phase 2 Results DMC

• 1 other identifier: 121971
• Study Type: interventional
• Target: 160
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Down Syndrome; Intellectual Disability

Keywords

Memantine; Episodic Memory; CVLT; Hippocampus dependent memory; Short-term memory

Outcome Measures

Primary Outcomes (1)

• Efficacy of the Drug Memantine as Assessed by Change in Score on the California Verbal Learning Test-II (CVLT-II) Short Form Total Free Recall

  The primary efficacy measure is focused on episodic memory. The CVLT-II short form assesses supraspan word learning ability as an index of episodic verbal long-term memory. We hypothesize that treatment with memantine will produce significant improvements in this test. The main dependent variable selected, based on prior literature was the total number of target items correct summed across learning trials 1-4. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2). Scale Range: from 0 to 36; higher scores represent better outcomes.

  baseline and 16 weeks from start of treatment

Secondary Outcomes (7)

• Efficacy of the Drug Memantine as Assessed by Change in Score on the Paired Associates Learning (PAL) From the Cambridge Neuropsychological Test Automated Battery (CANTAB)

  baseline and 16 weeks from start of treatment

• Efficacy of the Drug Memantine as Assessed by Change in Score on the Recall of Digits Forward (From the Differential Ability Scales; DAS-II)

  baseline and 16 weeks from start of treatment

• Efficacy of the Drug Memantine as Assessed by Change in Score on the Pattern Recognition Memory (PRM; Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)

  baseline and 16 weeks from start of treatment

• Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Working Memory (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)

  baseline and 16 weeks from start of treatment

• Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Span (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)

  baseline and 16 weeks from start of treatment

Other Outcomes (4)

• Intellectual Functioning of the Participants as Assessed by Change in Score on the Matrices Subtest of the Differential Ability Scales-II (DAS-II)

  baseline and 16 weeks from start of treatment

• Linguistic Functioning of the Participants as Assessed by Change in Score on the Test for Reception of Grammar 2nd Edition (TROG-II)

  baseline and 16 weeks from start of treatment

• Linguistic Functioning of the Participants as Assessed by Change in Score on the Peabody Picture Vocabulary Test-IV (PPVT-IV)

  baseline and 16 weeks from start of treatment

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Identically-looking placebo pills to memantine will be dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3.

Drug: Placebo

Memantine

EXPERIMENTAL

Memantine will be dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3.

Drug: Memantine

Interventions

Memantine DRUG

Encapsulated Namenda 10 mg bid (after four-week standard dose titration protocol)

Also known as: Namenda

Memantine

Placebo DRUG

Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)

Also known as: Inactive Capsules

Placebo

Eligibility Criteria

• Age: 15 Years - 32 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Cytogenetically documented Trisomy 21 or Complete Unbalanced Translocation of Chromosome 21. Mosaic Trisomy 21 and partial translocations will be excluded from the study
• No pregnancy by serum testing at screening. Females of child-bearing potential, sexually active must be practicing a reliable method of birth control. Urine pregnancy tests will be done at the 2 follow-up medical visits
• Laboratory findings within normal limits or judged clinically insignificant at baseline
• Vital signs within normal limits for age. Stable, medically treated hypotension will be allowed
• ECG must demonstrate predominately normal sinus rhythm. Minor abnormalities documented as clinically insignificant will be allowed
• Participants and their authorized representatives will provide written informed consent
• Participants who have received any experimental drug for Down syndrome must undergo a washout
• All participants must: Be in general good health as judged by the investigators; Be able to swallow oral medication; Have a reliable caregiver or family member who agrees to accompany participant to all visits, provide information about the participant as required by the protocol, and ensure compliance with the medication schedule; Be sufficiently proficient in English (USA) or Portuguese (Brazil) to reliably complete the study assessments
• Age and gender matching participants without Down syndrome, must be: Males or females without Down syndrome aged-matching (within 3 years) participants with Down syndrome whom they are expected to serve as controls

You may not qualify if:

• Participant weighing less than 40 kg
• Current psychiatric or neurologic diagnosis other than Down syndrome (e.g., major depressive disorder, schizophrenia, bipolar disorder, autism, Alzheimer disease)
• Current treatment with psychotropic drugs
• Drug or alcohol abuse or dependence
• Significant suicide risk or who would require treatment with electro-convulsive therapy or with psychotropic drugs during the study or who have received treatment with a depot neuroleptic drug within 6 months of entering the study.
• Current or expected (within the next 6 months) hospitalization or residence in a skilled nursing facility (may reside in group homes or other residential settings with no skilled nursing)
• Active or clinically significant conditions affecting absorption, distribution, or metabolism of study drug (e.g. inflammatory bowel disease or celiac disease)
• Significant allergies to or other significant intolerance of memantine therapy, its ingredients, or with contraindications to memantine therapy as stated in the prescribing information
• Participants who are expected to require general anesthetics during the course of the study
• Presence or recent history of seizure disorder (\< 3 years).
• Clinically significant and/or clinically unstable systemic disease. (Those with controlled hypothyroidism must be on a stable dose of medication for at least 3 months prior to screening and have normal serum T-4 and TSH at screening; and those with controlled diabetes mellitus must have an HbA1c of \< 8.0% and a random serum glucose value of \< 170 mg/dl)
• Severe infections or a major surgical operation within 3 months prior to screening
• History of persistent cognitive deficits immediately following head trauma.
• Donation of blood or blood products less that 30 days prior to screening, while participating in the study, or four weeks after completion of the study
• Inability to comply with the protocol or perform the outcomes measures due to significant hearing or visual impairment or other issues judged relevant by the investigators

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Alana USA Foundation: collaborator

Study Sites (2)

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Sociedade Beneficente Israelita Brasileira Albert Einstein

São Paulo, São Paulo, 05652- 900, Brazil

Location

Related Publications (61)

• 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.

  PMID: 11706811 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.

  PMID: 15077706 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.

  PMID: 22806212 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.

  PMID: 15755306 BACKGROUND

• Carr J. Six weeks to twenty-one years old: a longitudinal study of children with Down's syndrome and their families. Third Jack Tizard memorial lecture. J Child Psychol Psychiatry. 1988 Jul;29(4):407-31. doi: 10.1111/j.1469-7610.1988.tb00734.x.

  PMID: 2975288 BACKGROUND

• Carr J. Stability and change in cognitive ability over the life span: a comparison of populations with and without Down's syndrome. J Intellect Disabil Res. 2005 Dec;49(Pt 12):915-28. doi: 10.1111/j.1365-2788.2005.00735.x.

  PMID: 16287480 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.

  PMID: 21743130 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.

  PMID: 17690064 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.

  PMID: 23821040 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.

  PMID: 17700645 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.

  PMID: 22646481 BACKGROUND

• Erickson CA, Mullett JE, McDougle CJ. Open-label memantine in fragile X syndrome. J Autism Dev Disord. 2009 Dec;39(12):1629-35. doi: 10.1007/s10803-009-0807-3. Epub 2009 Jul 16.

  PMID: 19609663 BACKGROUND

• Erickson CA, Posey DJ, Stigler KA, Mullett J, Katschke AR, McDougle CJ. A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology (Berl). 2007 Mar;191(1):141-7. doi: 10.1007/s00213-006-0518-9. Epub 2006 Oct 3.

  PMID: 17016714 BACKGROUND

• Fernandez G, Weyerts H, Schrader-Bolsche M, Tendolkar I, Smid HG, Tempelmann C, Hinrichs H, Scheich H, Elger CE, Mangun GR, Heinze HJ. Successful verbal encoding into episodic memory engages the posterior hippocampus: a parametrically analyzed functional magnetic resonance imaging study. J Neurosci. 1998 Mar 1;18(5):1841-7. doi: 10.1523/JNEUROSCI.18-05-01841.1998.

  PMID: 9465008 BACKGROUND

• Findling RL, McNamara NK, Stansbrey RJ, Maxhimer R, Periclou A, Mann A, Graham SM. A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type. J Child Adolesc Psychopharmacol. 2007 Feb;17(1):19-33. doi: 10.1089/cap.2006.0044.

  PMID: 17343551 BACKGROUND

• Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer's disease: a review of progress. J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):137-47. doi: 10.1136/jnnp.66.2.137.

  PMID: 10071091 BACKGROUND

• Hanney M, Prasher V, Williams N, Jones EL, Aarsland D, Corbett A, Lawrence D, Yu LM, Tyrer S, Francis PT, Johnson T, Bullock R, Ballard C; MEADOWS trial researchers. Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial. Lancet. 2012 Feb 11;379(9815):528-36. doi: 10.1016/S0140-6736(11)61676-0. Epub 2012 Jan 10.

  PMID: 22236802 BACKGROUND

• Hosenbocus S, Chahal R. Memantine: a review of possible uses in child and adolescent psychiatry. J Can Acad Child Adolesc Psychiatry. 2013 May;22(2):166-71.

  PMID: 23667364 BACKGROUND

• Hu NW, Ondrejcak T, Rowan MJ. Glutamate receptors in preclinical research on Alzheimer's disease: update on recent advances. Pharmacol Biochem Behav. 2012 Feb;100(4):855-62. doi: 10.1016/j.pbb.2011.04.013. Epub 2011 Apr 22.

  PMID: 21536064 BACKGROUND

• Jarrold C, Baddeley AD, Hewes AK. Verbal short-term memory deficits in Down syndrome: a consequence of problems in rehearsal? J Child Psychol Psychiatry. 2000 Feb;41(2):233-44.

  PMID: 10750549 BACKGROUND

• Javitt DC, Steinschneider M, Schroeder CE, Arezzo JC. Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11962-7. doi: 10.1073/pnas.93.21.11962.

  PMID: 8876245 BACKGROUND

• Kaindl AM, Degos V, Peineau S, Gouadon E, Chhor V, Loron G, Le Charpentier T, Josserand J, Ali C, Vivien D, Collingridge GL, Lombet A, Issa L, Rene F, Loeffler JP, Kavelaars A, Verney C, Mantz J, Gressens P. Activation of microglial N-methyl-D-aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain. Ann Neurol. 2012 Oct;72(4):536-49. doi: 10.1002/ana.23626.

  PMID: 23109148 BACKGROUND

• Kew JN, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl). 2005 Apr;179(1):4-29. doi: 10.1007/s00213-005-2200-z. Epub 2005 Feb 25.

  PMID: 15731895 BACKGROUND

• Kornhuber J, Kennepohl EM, Bleich S, Wiltfang J, Kraus T, Reulbach U, Meineke I. Memantine pharmacotherapy: a naturalistic study using a population pharmacokinetic approach. Clin Pharmacokinet. 2007;46(7):599-612. doi: 10.2165/00003088-200746070-00005.

  PMID: 17596105 BACKGROUND

• Korostenskaja M, Nikulin VV, Kicic D, Nikulina AV, Kahkonen S. Effects of NMDA receptor antagonist memantine on mismatch negativity. Brain Res Bull. 2007 May 30;72(4-6):275-83. doi: 10.1016/j.brainresbull.2007.01.007. Epub 2007 Feb 2.

  PMID: 17452287 BACKGROUND

• Leverenz JB, Raskind MA. Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Exp Neurol. 1998 Apr;150(2):296-304. doi: 10.1006/exnr.1997.6777.

  PMID: 9527899 BACKGROUND

• Li S, Mallory M, Alford M, Tanaka S, Masliah E. Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression. J Neuropathol Exp Neurol. 1997 Aug;56(8):901-11. doi: 10.1097/00005072-199708000-00008.

  PMID: 9258260 BACKGROUND

• Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D. Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron. 2009 Jun 25;62(6):788-801. doi: 10.1016/j.neuron.2009.05.012.

  PMID: 19555648 BACKGROUND

• Lieberman DN, Mody I. Regulation of NMDA channel function by endogenous Ca(2+)-dependent phosphatase. Nature. 1994 May 19;369(6477):235-9. doi: 10.1038/369235a0.

  PMID: 7514273 BACKGROUND

• Lockrow J, Boger H, Bimonte-Nelson H, Granholm AC. Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome. Behav Brain Res. 2011 Aug 10;221(2):610-22. doi: 10.1016/j.bbr.2010.03.036. Epub 2010 Apr 2.

  PMID: 20363261 BACKGROUND

• Marczynski TJ. GABAergic deafferentation hypothesis of brain aging and Alzheimer's disease; pharmacologic profile of the benzodiazepine antagonist, flumazenil. Rev Neurosci. 1995 Jul-Sep;6(3):221-58. doi: 10.1515/revneuro.1995.6.3.221.

  PMID: 8717636 BACKGROUND

• Naatanen R. The mismatch negativity: a powerful tool for cognitive neuroscience. Ear Hear. 1995 Feb;16(1):6-18.

  PMID: 7774770 BACKGROUND

• Naatanen R. Mismatch negativity (MMN) as an index of central auditory system plasticity. Int J Audiol. 2008 Nov;47 Suppl 2:S16-20. doi: 10.1080/14992020802340116.

  PMID: 19012108 BACKGROUND

• Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Anderson P, Mason CA, Collins JS, Kirby RS, Correa A; National Birth Defects Prevention Network. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol. 2010 Dec;88(12):1008-16. doi: 10.1002/bdra.20735. Epub 2010 Sep 28.

  PMID: 20878909 BACKGROUND

• Parsons CG, Stoffler A, Danysz W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system--too little activation is bad, too much is even worse. Neuropharmacology. 2007 Nov;53(6):699-723. doi: 10.1016/j.neuropharm.2007.07.013. Epub 2007 Aug 10.

  PMID: 17904591 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.

  PMID: 15640809 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.

  PMID: 12625437 BACKGROUND

• Petrides M, Milner B. Deficits on subject-ordered tasks after frontal- and temporal-lobe lesions in man. Neuropsychologia. 1982;20(3):249-62. doi: 10.1016/0028-3932(82)90100-2.

  PMID: 7121793 BACKGROUND

• Picton TW, Alain C, Otten L, Ritter W, Achim A. Mismatch negativity: different water in the same river. Audiol Neurootol. 2000 May-Aug;5(3-4):111-39. doi: 10.1159/000013875.

  PMID: 10859408 BACKGROUND

• Roizen NJ, Patterson D. Down's syndrome. Lancet. 2003 Apr 12;361(9365):1281-9. doi: 10.1016/S0140-6736(03)12987-X.

  PMID: 12699967 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.

  PMID: 20421694 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.

  PMID: 22784018 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.

  PMID: 22101180 BACKGROUND

• Seow D, Gauthier S. Pharmacotherapy of Alzheimer disease. Can J Psychiatry. 2007 Oct;52(10):620-9. doi: 10.1177/070674370705201003.

  PMID: 18020110 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.

  PMID: 10877432 BACKGROUND

• Swainson R, Hodges JR, Galton CJ, Semple J, Michael A, Dunn BD, Iddon JL, Robbins TW, Sahakian BJ. Early detection and differential diagnosis of Alzheimer's disease and depression with neuropsychological tasks. Dement Geriatr Cogn Disord. 2001 Jul-Aug;12(4):265-80. doi: 10.1159/000051269.

  PMID: 11351138 BACKGROUND

• Tayeb HO, Yang HD, Price BH, Tarazi FI. Pharmacotherapies for Alzheimer's disease: beyond cholinesterase inhibitors. Pharmacol Ther. 2012 Apr;134(1):8-25. doi: 10.1016/j.pharmthera.2011.12.002. Epub 2011 Dec 16.

  PMID: 22198801 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.

  PMID: 20298759 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.

  PMID: 17497670 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.

  PMID: 14713378 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.

  PMID: 18205756 BACKGROUND

• Umbricht D, Schmid L, Koller R, Vollenweider FX, Hell D, Javitt DC. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia. Arch Gen Psychiatry. 2000 Dec;57(12):1139-47. doi: 10.1001/archpsyc.57.12.1139.

  PMID: 11115327 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.

  PMID: 14723651 BACKGROUND

• Vicari S, Caselli MC, Gagliardi C, Tonucci F, Volterra V. Language acquisition in special populations: a comparison between Down and Williams syndromes. Neuropsychologia. 2002;40(13):2461-70. doi: 10.1016/s0028-3932(02)00083-0.

  PMID: 12417473 BACKGROUND

• Zigman W, Schupf N, Haveman M, Silverman W. The epidemiology of Alzheimer disease in intellectual disability: results and recommendations from an international conference. J Intellect Disabil Res. 1997 Feb;41 ( Pt 1):76-80. doi: 10.1111/j.1365-2788.1997.tb00679.x.

  PMID: 9089462 BACKGROUND

• Zigman WB, Lott IT. Alzheimer's disease in Down syndrome: neurobiology and risk. Ment Retard Dev Disabil Res Rev. 2007;13(3):237-46. doi: 10.1002/mrdd.20163.

  PMID: 17910085 BACKGROUND

• Costa AC. Alzheimer disease: Treatment of Alzheimer disease in Down syndrome. Nat Rev Neurol. 2012 Mar 13;8(4):182-4. doi: 10.1038/nrneurol.2012.40. No abstract available.

  PMID: 22410580 BACKGROUND

• Choi DW. Excitotoxic cell death. J Neurobiol. 1992 Nov;23(9):1261-76. doi: 10.1002/neu.480230915.

  PMID: 1361523 BACKGROUND

• Brandão IM, V. F, R. MR (2012) Prevalence of People with Down Syndrome in Brazil. In: Scientia Plena (www.scientiaplena.org.br).

  BACKGROUND

• Pueschel SM, Hopmann MR (1993) Speech and language abilities of children with Down syndrome. In: Enhancing children's communication: Research foundations for intervention (Kaisen AP, Gray DB, eds), pp 335-362. London: Brookes.

  BACKGROUND

• 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.

  PMID: 34942135 RESULT

MeSH Terms

Conditions

Down Syndrome; Intellectual Disability

Interventions

Memantine

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Melissa Stasko, JD, MA
• Organization: Case Western Reserve University

Melissa.Stasko@case.edu

216-844-7281

Study Officials

• Alberto C Costa, MD, PhD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

• Stephen L Ruedrich, MD

  University Hospitals Cleveland Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2014
• First Posted: December 1, 2014
• Study Start: October 1, 2014
• Primary Completion: July 22, 2020
• Study Completion: July 22, 2020
• Last Updated: June 27, 2023
• Results First Posted: April 5, 2022

Record last verified: 2022-04

Locations

US (1); BR (1)