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Clinical Trials in Dementia

Published online by Cambridge University Press:  13 June 2006

Encarnita Raya-Ampil  and
Jeffrey L. Cummings
Encarnita Raya-Ampil
Affiliation:
Department of Neurology and Psychiatry, University of Santo Tomas, Manila, Philippines; Email: [email protected]
Jeffrey L. Cummings
Affiliation:
Departments of Neurology and Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Email: [email protected]
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Extract

ABSTRACT

Dementia, particularly Alzheimer's disease (AD), is increasing by patient population included in clinical trials. The methodology for trials of AD patients have been defined in terms of outcomes, standard measures and analytic techniques. Trial methodology is evolving with experience as new potential therapies become available. Screening criteria, instrumentation choices, duration of trials and analytic strategies may have a profound impact on the conclusions that can be derived from trials. The components of AD trials are reviewed in detail in this chapter.

Type
Review Article
Information
Progress in Neurotherapeutics and Neuropsychopharmacology , Volume 2 , Issue 1 , March 2007 , pp. 39 - 78
Copyright
© 2007 Cambridge University Press

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References

A Randomized Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Galantamine in Subjects with Mild Cognitive Impairment (MCI) Clinically at Risk for Development of Clinically Probably Alzheimer's Disease. Gal-INT-18 and Gal-INT-11. http://www.alz.org/news/05q1/012405.asp. Accessed on November 17, 2005.
AD2000 Collaborative Group (2004). Long term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomized double-blind trial. Lancet, 353, 2105–2115.Google Scholar
Aisen, P., Davis, K., Berg, J., et al. (2000). A randomized controlled trial of prednisone in Alzheimer's disease. Neurology, 54, 588–593.Google Scholar
Aisen, P., Schafer, K., Grundman, M., et al. (2003). Effects of rofecoxib or naproxen vs. placebo on Alzheimer disease progression. Journal of the American Medical Association, 289, 2819–2826.Google Scholar
Alexopoulos, G., Abrams, R., Young, R., et al. (1988). Cornell Scale for depression in dementia. Biological Psychiatry, 23, 271–284.Google Scholar
Alzheimer Association (2004). Research consent for cognitively impaired adults: recommendations for institutional review boards and investigators. Alzheimer Disease & Associated Disorders, 18, 171–175.Google Scholar
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Washington, DC: American Psychiatric Association, 143–147.
Begg, C., Cho, M., Eastwood, S., et al. (1996). Improving the quality of reporting of randomized controlled trials: the CONSORT statement. Journal of the American Medical Association, 276, 637–639.Google Scholar
Blacker, D., Albert, M., Bassett, S., et al. (1994). Reliability and validity of NINCDS–ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative. Archives of Neurology, 51, 1198–1204.Google Scholar
Brodaty, H., Ames, D., Snowdon, J., et al. (2003). A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation and psychosis of dementia. Journal of Clinical Psychiatry, 64, 134–143.Google Scholar
Burke, W., Miller, O., Rubin, E., et al. (1988). Reliability of the Washington University Clinical Dementia Rating. Archives of Neurology, 45, 31–32.Google Scholar
Cohen-Mansfield, J. (1985). Agitated behaviors in the elderly ill. Preliminary results in the cognitively deteriorated. Journal of the American Geriatrics Society, 34, 722–727.Google Scholar
Corey-Bloom, J., Anand, R., Veach, J., et al. (1998). A randomized trial evaluating the efficacy and safety of ENA 73 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. International Journal of Geriatric Psychopharmacology, 1, 55–65.Google Scholar
Cummings, J. (2003). Use of acetylcholinesterase inhibitors in clinical practice: evidence-based recommendations. American Journal of Geriatric Psychiatry, 11, 131–145.Google Scholar
Cummings, J., Mega, M., Gray, K., et al. (1994). The neuropsyciatric inventory: an efficient tool for comprehensively assessing psychopathology in dementia. Neurology, 44, 2308–2314.Google Scholar
Cummings, J., Cyrus, P., Bieber, F., et al. (1998). Metrifonate treatment of the cognitive deficits of Alzheimer's disease. Neurology, 50, 1214–1221.Google Scholar
Davis, K., Thal, L., Gamzu, E., et al. (1992). A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. New England Journal of Medicine, 327, 1253–1259.Google Scholar
Davis, K., Marin, D., Kane, R., et al. (1997). The Caregiver Activity Survey (CAS): development and validation of a new measure for caregivers of persons with Alzheimer's disease. International Journal of Geriatric Psychiatry, 12, 978–988.Google Scholar
De Deyn, P., Rabheru, K., Rasmussen, A., et al. (1999). A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology, 53, 946–955.Google Scholar
DeJong, R., Osterlund, O., Roy, G. (1989). Measurement of quality-of-life changes in patients with Alzheimer's disease. Clinical Therapeutics, 11, 545–554.Google Scholar
Doody, R., Stevens, J., Beck, C., et al. (2001). Practice parameter: management of dementia (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56, 1154–1166.Google Scholar
Doraiswamy, P., Kaiser, L., Bieber, F., et al. (2001). The Alzheimer's Disease Assessment Scale: evaluation of psychometric properties and patterns of cognitive decline in multicenter clinical trials of mild-to-moderate Alzheimer's disease. Alzheimer Disease & Associated Disorders, 15, 174–183.Google Scholar
Ernst, R.L. & Hay, J.W. (1994). The US economic and social costs of AD revisited. American Journal of Public Health, 84, 1261–1264.Google Scholar
Evans, D.A. (1990). Estimated prevalence of Alzheimer's disease in the United States. Milbank Q 68, 267–289.Google Scholar
Evans, D.A., Funkenstein, H.H., Albert, M.S., et al. (1989). Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. Journal of the American Medical Association, 26, 2551–2556.Google Scholar
Everitt, B. Pickler, A. (2004). Statistical Aspects of the Design and Analysis of Clinical Trials. London: Imperial College Press, pp. 45–50, 203–204.
Farlow, M., Gracon, S., Hershey, L., et al. (1992). A controlled trial of tacrine in Alzheimer's disease. Journal of the American Medical Association, 268, 2523–2529.Google Scholar
Feldman, H., Gauthier, S., Hecker, J., et al. (2001). A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease. Neurology, 57, 613–620.Google Scholar
Ferris, S., Lucca, U., Mohs, R., et al. (1997). Objective psychometric tests in clinical trials of dementia drugs. Alzheimer Disease & Associated Disorders, 11, 34–38.Google Scholar
Folstein, M., Folstein, S., McHugh, P. (1975). Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.Google Scholar
Galasko, D., Bennett, D., Sano, M., et al. (1997). An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. Alzheimer Disease & Associated Disorders, 11 (Suppl. 2), S33–S39.Google Scholar
Gauthier, S., Bodick, N., Erzigkeit, E., et al. (1997). Activities of daily living as an outcome measure in clinical trials of dementia drugs. Alzheimer Disease & Associated Disorders, 11 (Suppl. 3), 6–7.Google Scholar
Gelinas, I., Gauthier, L., McIntyre, M., et al. (1999). Development of a functional measure for persons with Alzheimer's disease: the disability assessment for dementia. Americal Journal of Occupational Therapy, 53, 471–481.Google Scholar
Guy, W. (ed.) (1976). Clinical Global Impression (CGI). ECDEU assessment manual for psychopharmacology. Rockville, MD: US Department of Health and Human Services, Public Health Service, Alcohol Drug Abuse and Mental Health Administration. NIMH Psychopharmacology Research Branch. pp. 218–222.
Holmes, C., Clairns, N., Lantos, P., et al. (1999). Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies. British Journal of Psychiatry, 174, 45–50.Google Scholar
Hughes, C., Berg, L., Denziger, W., et al. (1982). A new clinical scale for the staging of dementia. British Journal of Psychiatry, 140, 566–572.Google Scholar
Institute on Aging (1996). Progress Report on Alzheimer's Disease 1996. Bethesda, Md: National Institute on Aging, NIH publication, pp. 96–4137.
Katz, I., Jeste, D., Mintzer, J., et al. (1999). Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Journal of Clinical Psychiatry, 60, 107–115.Google Scholar
Kay, S., Opler, L., Lindenmayer, J., et al. (1989). The positive and negative syndrome scale: a rationale and standardization. British Journal of Psychiatry, 155 (Suppl. 7), 59–65.Google Scholar
Knapp, M., Knopman, D., Solomon, P., et al. (1994). A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. Journal of the American Medical Association, 271, 985–991.Google Scholar
Knopman, D., Knapp, M., Bracon, S., et al. (1994). The clinician interview-based impression (CIBI): a clinician's global change rating scale in Alzheimer's disease. Neurology, 44, 2315–2321.Google Scholar
Koepsell, T. Weiss, N. (2003). Epidemiologic Methods. New York: Oxford University Press, pp. 64–67, 261, 327–329.
Lawton, M. Brody, E. (1969). Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist, 9, 179–186.Google Scholar
Le Bars, P., Katz, M., Berman, N., et al. (1997). A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo Biloba for dementia. Journal of the American Medical Association, 278, 1327–1332.Google Scholar
Leber, P. (1990). Guidelines for the Clinical Evaluation of Antidementia Drugs, Food and Drug Administration, Washington, D.C.
Leber, P. (1997). Observations and suggestions on antidementia drug development. Alzheimer Disease & Associated Disorders, 10, S1, 31–35.Google Scholar
Lopez, O.L., Litvan, I., Catt, K.E., et al. (1999). Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementias. Neurology, 53, 1292–1299.Google Scholar
Lyketsos, C., Sheppard, J., Steele, C., et al. (2000). Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the depression in Alzheimer's disease study. American Journal of Psychiatry, 157, 1686–1689.Google Scholar
McKhann, G., Drachman, D., Folstein, M., et al. 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.
Moher, D., Schulz, K., Altman, D., et al. (2001). The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Journal of the American Medical Association, 285, 1987–1991.Google Scholar
Mohs, R., Doody, R., Morris, J., et al. (2001). A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology, 57, 481–488.Google Scholar
Morris, J., Edland, S., Clark, C., et al. (1993). The consortium to establish a registry for Alzheimer's disease (CERAD). Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer's disease. Neurology, 43, 2457–2465.Google Scholar
Morris, J., Cyrus, P., Orazem, J., et al. (1998). Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease. Neurology, 50, 1222–1230.Google Scholar
Morris, J.C., Storandt, M., Miller, P., et al. (2001). Mild cognitive impairment represents early-stage Alzheimer's disease. Archives of Neurology, 58, 397–405.Google Scholar
Mulnard, R., Cotman, C., Kawas, C., et al. (2000). Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease. Journal of the American Medical Association, 283, 1007–1015.Google Scholar
National Institute of Health, National Institute on Aging (1999). Progress Report on Alzheimer's Disease 1999 (NIH Pub. No. 99-4664). Bethesda, MD: US Department of Health and Human Services.
O'Connor, D.W., Pollitt, P., Hyde, J.B., et al. (1989). The reliability and validity of the mini-mental state in a British community survey. Journal of Psychiatric Research 23, 87–96.Google Scholar
Overall, J. Gorham, D. (1962). The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799–812.Google Scholar
Overall, J. Gorhal, D. (1988). Introduction: the Brief Psychiatric Rating Scale (BPRS): recent developments in ascertainment and scaling. Psychopharmacology Bulletin, 24, 97–99.Google Scholar
Patterson, M. Bolger, J. (1994). Assessment of behavioral symptoms in Alzheimer's disease. Alzheimer Disease & Associated Disorders, 8 (Suppl. 3), 4–20.Google Scholar
Petersen, R.C., Doody, R., Kurz, A., et al. (2001). Current concepts in mild cognitive impairment. Archives of Neurology, 58, 1985–1992.Google Scholar
Petersen, R.C., Thomas, R.G., Grundman, M., et al. (2005). Vitamin E and donepezil for the treatment of mild cognitive impairment. New England Journal of Medicine, 352, 2379–2388.Google Scholar
Porteinsson, A., Tariot, P., Erb, R., et al. (2001). Placebo-controlled study of divalproex sodium for agitation in dementia. American Journal of Geriatric Psychiatry 9, 58–66.Google Scholar
Raskind, M., Peskind, E., Wessel, T., et al. (2000). Galantamine in AD: a 6-month randomized, placebo-controlled trial with a 6-month extension. Neurology, 54, 2261–2268.Google Scholar
Reines, S., Block, G., Morris, J., et al. (2004). Rofecoxib: no effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study. Neurology, 62, 66–71.Google Scholar
Reisberg, B., Ferris, S., de Leon, M., et al. (1982). The Global Deterioration Scale for assessment of primary degenerative dementia. American Journal of Psychiatry, 138, 1136–1139.Google Scholar
Reisberg, B., Scaln, S., Franssen, E., et al. (1994). Dementia staging in chronic care populations. Alzheimer Disease & Associated Disorders, 8 (Suppl. 1), S188–S205.Google Scholar
Reisberg, B., Auer, S.R., Monteiro, I.M., et al. (1996). Behavioral pathology in Alzheimer's disease (BEHAVE-AD) rating scale. International Psychogeriatrics, 8 (Suppl. 3), 301–308.Google Scholar
Reisberg, B., Doody, R., Stoffler, A., et al. (2003). Memantine in moderate-to-severe Alzheimer's disease. New England Journal of Medicine, 348, 1333–1341.Google Scholar
Rockwood, K., Mintzer, J., Truyen, L., et al. (2001). Effects of a flexible galantamine dose in Alzheimer's disease: a randomized, controlled trial. Journal of Neurology Neurosurgery and Psychiatry, 71, 589–595.Google Scholar
Rogers, S., Doody, R., Mohs, R., et al. (1998a). Donepezil improves cognition and global function in Alzheimer's disease. Archives of Internal Medicine, 158, 1021–1031.Google Scholar
Rogers, S., Farlow, M., Doody, R., et al. (1998b). A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology, 50, 136–145.Google Scholar
Rosen, W., Mohs, R., Davis, K., et al. (1984). A new rating scale for Alzheimer's disease. American Journal of Psychiatry, 141, 1356–1364.Google Scholar
Rosler, M., Anand, R., Cicin-Sain, A., et al. (1999). Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomized controlled trial. British Medical Journal, 318, 633–638.Google Scholar
Salloway, S., Ferris, S., Kluger, A., et al. (2004). Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial. Neurology, 63, 651–657.Google Scholar
Sano, M., Ernesto, C., Klauber, M., et al. (1996). Rationale and design of a multicenter study of selegiline and A-tocopherol in the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer Disease & Associated Disorders, 10, 132–140.Google Scholar
Sano, M., Ernesto, C., Thomas, R., et al. (1997). A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. New England Journal of Medicine, 336, 1216–1222.Google Scholar
Scharf, S., Mander, A., Ugoni, A., et al. (1999). A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology, 53, 197–201.Google Scholar
Schneider, L., Olin, J., Doody, R., et al. (1997). Validity and reliability of the Alzheimer's disease cooperative study-Clinical Global Impression of change. Alzheimer Disease & Associated Disorders, 11 (Suppl. 2), S22–S32.Google Scholar
Schneider, L., Tariot, P., Lyketsos, C., et al. (2001). National Institute of Mental Health Clinical Antipsychotic Trial of Inervention Effectiveness (CATIE): Alzheimer disease trial methodology. American Journal of Geriatric Psychiatry, 9, 346–390.Google Scholar
Schoenmaker, N. & Van Gool, W. (2004). The age gap between patients in clinical studies and in the general population: a pitfall for dementia research. Lancet Neurology, 3, 627–630.Google Scholar
Tariot, P., Erb, R., Podgorski, C., et al. (1988). Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. American Journal of Psychiatry, 155, 54–61.Google Scholar
Tariot, P., Mack, J., Patterson, M., et al. and the CERAD Behavioral Pathology Committee (1995). The CERAD Behavior Rating Scale for Dementia (BRSD). American Journal of Psychiatry, 152, 1349–1357.Google Scholar
Tariot, P., Solomon, P., Morris, J., et al. (2000). A 5-month, randomized, placebo-controlled trial of galantamine in AD. Neurology, 54, 2269–2276.Google Scholar
Thal, L., Carta, A., Clarke, W., et al. (1996). A 1-year multicenter placebo-controlled study of acetyl-l-carnitine in patients with Alzheimer's disease. Neurology, 47, 705–711.Google Scholar
Tierney, M., Fisher, R., Anthony, J., et al. (1988). The NINCDS–ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases. Neurology, 38, 359–364.Google Scholar
Weiner, M., Koss, E., Wild, K., et al. (1996). Measures of psychiatric symptoms in Alzheimer patients: a review. Alzheimer Disease & Associated Disorders, 10, 20–30.Google Scholar
Whitehouse, P. (1997). Pharmacoeconomics of dementia. Alzheimer Disease & Associated Disorders, 11 (Suppl. 5), S22–S33.Google Scholar
Wimo, A., Wetterholm, A., Mastey, Y., et al. (1998). Evaluation of the healthcare resource utilization and caregiver time in anti-dementia drug trials. In: Wimo, A., Jonsson, B., Karlson, G., Wilblad, B. (eds.), Health Economics of Dementia. Chichester, England: John Wiley, 465–499.
Winblad, B., Wimo, A. Almkvist, O. (2000). Outcome measures in Alzheimer's disease: Do they go far enough? Dementia and Geriatric Cognitive Disorders, 11 (Suppl. 1), 3–10.Google Scholar
Winblad, B., Engedal, K., Soininen, H., et al. (2001). A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology, 57, 489–495.Google Scholar
World Health Organization (1993). The ICD-10 Classification of Mental and Behavioral Disorders. Diagnostic Criteria for Research. Geneva, Switzerland: World Health Organization.
Zhong, K., Tariot, P., Minkwitz, M.C., et al. (2004). Quetiapine for the treatment of agitation in the elderly institutionalized patients with dementia: a randomized, double blind trial. International Conference on Alzheimer's Disease and Related Disorders meeting, Poster # P2-442.Google Scholar