A multicentre, randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate Alzheimer's disease: The MALT study

International Journal of Geriatric Psychiatry

Volumn 14, Issue 11, 1999, Pages 973-982

  Dubois, Bruno ^a,f   McKeith, Ian ^b   Orgogozo, Jean Marc ^c   Collins, Owen ^d   Meulien, Didier ^e  

^a PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^b NEWCASTLE GENERAL HOSPITAL   (United Kingdom)

^c HÔPITAL PELLEGRIN   (France)

^d Bayer plc UK   (United Kingdom)

^e Bayer Pharma SA   (France)

^f Fed de Neurologie   (France)

Author keywords

Acetylcholinesterase inhibitor; Activities of daily living; Alzheimer's disease; Cognition; Global function; Metrifonate; Neuropsychiatric features

Indexed keywords

CHOLINESTERASE INHIBITOR; METRIFONATE;

AGED; ALZHEIMER DISEASE; ARTICLE; CLINICAL TRIAL; COGNITION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DAILY LIFE ACTIVITY; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; RANDOMIZED CONTROLLED TRIAL;

ACTIVITIES OF DAILY LIVING; AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; CHOLINESTERASE INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HUMANS; MENTAL STATUS SCHEDULE; NEUROPSYCHOLOGICAL TESTS; PROSPECTIVE STUDIES; TREATMENT OUTCOME; TRICHLORFON;

EID: 0032749775     PISSN: 08856230     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1099-1166(199911)14:11<973::AID-GPS58>3.0.CO;2-U     Document Type: Article

References (35)

1. American Psychiatric Association 1994 Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV). American Psychiatric Association, Washington, DC.
2. Anand R, Gharabawi G, Enz A. 1996. Efficacy and safety results of the early phase studies with Exelon (ENA-713) in Alzheimer's disease: an overview. J. Drug Dev. Clin. Pract. 8, 1-8.
3. Becker RE, Colliver J, Elble R, Feldman E, Giacobini E, Kumar V, Markwell S, Moriearty P, Parks R, Shillcutt SD, Unni L, Vicari S, Womack C, Zec RF. 1990. Effects of metrifonate, a long-acting cholinesterase inhibitor, in Alzheimer's disease: report of an open trial. Drug. Dev. Res. 19, 425-434.
4. Brufani M, Filocamo L, Lappa S, Maggi A. 1997. New acetylcholinesterase inhibitors. Drugs of the Future 22, 397-410.
5. Corey-Bloom C, Anand R, Veach J for the ENA-713 B352 Study Group (1998) A randomized trial evaluating the efficacy and safety of ENA 713 (rivastagmine tartate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. Int. J. Geriatr. Psychopharmacol. 1, 55-65.
6. CPMP Note for Guidance on Medicinal Products in the Treatment of Alzheimer's Disease. July 1997.
7. Cummings JL, Cyrus PA, Bieber F, Mas J, Orazem J, Gulanski B. 1998. Metrifonate treatment of the cognitive deficits of Alzheimer's disease. Neurology 50, 1214-1221.
8. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carus DA, Gornbein J. 1994. Neuropsychiatric inventory - comprehensive assessment of psychopathology in dementia. Neurology 44, 2308-2314.
9. Data on File. Bayer AG.
10. Farlow M, Gracon SI, Hershey LA, Lewis KW, Sadowsky CH, Dolan-Ureno J. 1992. A controlled trial of tacrine in Alzheimer's disease. JAMA 268, 2523-2529.
11. F-D-C Reports 'The Pink Sheet' (Trade and Government Memos). 1992. Salem (MA): FDC Report, Inc.; March 2.
12. Folstein MF, Folstein SE, McHugh PR. 1975. Minimental state: a practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189-198.
13. Gélinas I, Auer S. 1996. Functional autonomy. In: Clinical Diagnosis and Management of Alzheimer's Disease (S Gauthier, Ed). Martin Dunitz Ltd, London.
14. Giacobini E. 1997. From molecular structure to Alzheimer therapy. Jpn J. Pharmacol. 74, 225-241.
15. Heinig R, Versavel M, Breuel HP, Kuhlmann J. 1997. Rapid attainment of steady-state acetylcholinesterase inhibition by administration of metrifonate loading and maintenance doses once-daily in elderly volunteers. Biol. Psychiatry 42, 94S.
16. Hinz VC, Kolb J, Schmidt BH. 1996a. Metrifonate, induces cholinesterase inhibition exclusively via slow release of dichlorvos. Neurochem. Res. 21, 331-337.
17. Hinz VC, Grewig S, Schmidt BH. 1996b. Metrifonate and dichlorvos: effects of a single oral administration on cholinesterase activity in rat brain and blood. Neurochem. Res. 21, 339-345.
18. Hinz VC, Grewig S, Schmidt BH. 1998. Effects of subchronic administration of metrifonate on cholinergic neurotransmission in rats. Neurochem. Res. 23, 931-938.
19. Hochberg Y. 1988. A sharper Bonferroni procedure for multiple tests of significance. Biometrika 75, 800-802.
20. Jann MW, Cyrus PA, Eisner LS, Margolin DI, Griffin T, Gulanski B. 1999. Efficacy and safety of a loading dose regimen versus a no-loading dose regimen of metrifonate in the symptomatic treatment of Alzheimer's disease. A randomised double masked placebo controlled trial. Metrifonate Study Group. Clin. Ther. 21(1), 88-102.
21. Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI 1994. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. JAMA 27, 985-991.
22. Kronforst-Collins MA, Moriearty PL, Ralph M, Becker RE, Schmidt B, Thompson LT et al. 1997. Metrifonate treatment enhances acquisition of eyeblink conditioning in aging rabbits. Pharmacol. Biochem. Behav. 56, 103-110.
23. Leber P. Letter to sponsors recommending use of CIBIC in dementia trials. 1990a. Rockeville (MD): US Food and Drug Administration.
24. Leber P. Guidelines for the clinical evaluation of anti-dementia drugs. 1990b. First draft. Rockeville (MD): US Food and Drug Administration.
25. McKhann G, Drachman D, Folstein M, Katzman R, Price D., Stadlan EM. 1984. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 34, 939-944.
26. Morich FJ, Bieber F, Lewis JM, Kaiser L, Cutler NR, Escobar JI, Willmer J, Peterson RC, Reisberg B. 1996. North American Nimodipine Study Group. Nimodipine in the treatment of probable Alzheimer's disease. Results of two multicentre trials. Clin. Drug Invest. 11, 185-195.
27. Morris JC, Cyrus PA, Orazem J, Mas J, Bieber F, Ruzicka BB. 1998. Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease. Neurology 50, 1222-1230.
28. Nordgren I, Holmstedt B, Bengtsson B, Finkel Y. 1980. Plasma levels of metrifonate and dichlorvos during treatment of schistosomiasis with Bilarcil. Am. J. Med. Trop. Hyg. 29, 426.
29. Reisberg B, Ferris SH, DeLeon MJ, Crook T. 1982. The global deterioration scale for assessment of primary degenerative dementia. Am. J. Psychiatry 139, 1136-1139.
30. Rogers SL, Farlow MR, Doody RS, Mohrs R, Friedhoff LT. 1998. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology 50, 136-145.
31. Rogers SL, Friedhoff LT. 1996. The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US multicentre, randomized, double-blind, placebo-controlled trial. Dementia 7, 293-303.
32. Rosen WG, Mohs RC, Davis KL. 1984. A new rating scale for Alzheimer's disease. Am. J. Psychiatry 141, 1356-1364.
33. Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A. 1980. Pathological verification of ischemic score in differentiation of dementias. Ann. Neurol. 7, 486-488.
34. Schmidt BH, Hinz VC, Blokland A, van der Staay FJ, Fanelli R. 1996. Preclinical pharmacology of metrifonate: a promise for Alzheimer therapy. Alzheimer's Disease: From Molecular Biology to Therapy (RE Becker, E Giacobini, R Robert, Eds). Birkhäuser, Boston.
35. Thal LJ, Maasur DM, Fuld PA, Sharpless NS, Davies P. 1983. Memory improvement with oral physostigmine and lecithin in Alzheimer's disease. In: Banbury Report: Biological Aspects of Alzheimer's disease, (R Katzman, Ed.). 9th ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.