PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 10556869

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.

B Dubois·I McKeith·J M Orgogozo·O Collins·D Meulien
View original source ↗Export metadata ↓

Abstract

BACKGROUND: Metrifonate is a long-lasting acetylcholinesterase inhibitor being developed for the symptomatic treatment of Alzheimer's disease (AD). OBJECTIVES: This study compared the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate AD, over a 26-week treatment period. METHODS: Six hundred and five patients were randomized to placebo (n=208), a 40/50 mg dose (40 or 50 mg by weight; n=200) or a 60/80 mg dose (60 or 80 mg by weight; n=197) metrifonate. Patients randomized to receive metrifonate were administered a once-daily loading dose of 80 or 120 mg based on weight for 2 weeks, followed by the relevant maintenance dose for 24 weeks. Four main clinical domains of AD were assessed: cognition (ADAS-cog and MMSE), psychiatric and behavioural symptoms (ADAS-noncog and NPI), instrumental and basic activities of daily living (DAD) and global functioning (CIBIC-plus, CIBIS-plus and GDS). RESULTS: ADAS-cog performance was significantly improved in the 60/80 mg and 40/50 mg dose groups, compared with placebo, in the intention-to-treat (ITT) population. In addition, statistically significant treatment differences were demonstrated between the 60/80 mg dose group and placebo on MMSE, ADAS-noncog, the NPI subitems of hallucinations and apathy, DAD, CIBIC-plus, CIBIS-plus and the GDS. The performance of the 40/50 mg dose group was also significantly superior to placebo on the CIBIS-plus and the NPI subitem aberrant motor behaviour. CONCLUSIONS: Metrifonate significantly improved a wide range of symptoms across all four clinical domains of AD in a dose-dependent manner, and was safe and well tolerated at both doses studied.

Explore related subjects

Activities of Daily LivingAgedAged, 80 and overAlzheimer DiseaseCholinesterase InhibitorsDose-Response Relationship, DrugDouble-Blind MethodHumansMental Status ScheduleNeuropsychological TestsProspective StudiesTreatment OutcomeTrichlorfonClinical TrialComparative StudyJournal ArticleMulticenter StudyRandomized Controlled TrialResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

B Dubois, I McKeith, J M Orgogozo, O Collins, D Meulien. 1999. 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.. https://pubmed.ncbi.nlm.nih.gov/10556869/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

A pooled analysis of quality of life measures and adverse events data in north central cancer treatment group lung cancer clinical trials.

BACKGROUND: In this pooled analysis, the authors examined correlations between single-item and multiple-item quality of life (QOL) measures and assessed the agreement between clinically significant changes in QOL and patient-reported adverse events (AE). METHODS: Data from 6 lung cancer clinical trials that involved 358 patients were pooled. All trials incorporated the Uniscale and 1 of 3 multiple-item assessments: the Functional Assessment for Cancer Therapy-Lung, the Lung Cancer Symptom Scale, or the Symptom Distress Scale. Spearman rank correlations and a Bland-Altman approach were used to assess agreement. Time-to-event analysis was performed using the Kaplan-Meier method. RESULTS: Correlations between the Uniscale and multiple-item assessments were substantial (correlation coefficient = 0.49-0.66). At least 1 10-point decline was reported in the Uniscale and multiple-item assessments by 58% of patients and 39% of patients, respectively. At least 1 severe AE (grade >or=3) was reported in 35% of patients postbaseline. The percent agreement between experiencing a severe AE and a decline in QOL was 48% and 59% for the Uniscale and multiple-item assessments, respectively. The median time to the first 10-point decline in QOL for the Uniscale and multiple-item assessments was 67 days and 142 days, respectively, and the median time to the first occurrence of a severe AE was 304 days. CONCLUSIONS: Information gleaned from the single-item Uniscale assessment was comparable to that gleaned from multiple-item global measures. There was moderate agreement between QOL and AE. A 10-point decline in QOL occurred earlier than Common Toxicity Criteria AE reporting. This suggests the need for inclusion of a QOL instrument in lung cancer clinical trials.

Activities of Daily Living↗
PubMed2007

A pilot study of the vulnerable elders survey-13 compared with the comprehensive geriatric assessment for identifying disability in older patients with prostate cancer who receive androgen ablation.

BACKGROUND: Impairments in geriatric domains adversely affect health outcomes of the elderly. The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients, but it is time consuming. In this pilot study, the authors evaluated the validity of a brief, functionally based screening tool, the Vulnerable Elders Survey-13 (VES-13), for identifying older patients with prostate cancer (PCa) with impairment in the oncology clinic setting. METHODS: Patients with PCa aged >or=70 years who actively were receiving androgen ablation treatment and who were followed within the clinics at the University of Chicago were eligible. Patients self-completed the VES-13 and CGA instruments and repeated the VES-13 1 month later. Physical performance and cognitive assessments were administered by a research assistant. RESULTS: Of 50 participating patients, 50% were identified as impaired by the VES-13 (score >or=3). Sixty percent of patients scored as impaired on >or=2 tests within the CGA, exhibiting deficits in multiple domains. The reliability of the VES-13 (Pearson correlation coefficient) was 0.92. The cut-off score of 3 on the VES-13 had 72.7% sensitivity and 85.7% specificity for CGA deficits and was highly predictive for identifying impairment (area under the receiver operating characteristic curve, 0.90). Patients who had mean VES-13 scores >or=3 performed significantly worse on evaluations of activities of daily living (P = .001), physical performance (P = .002), comorbidity (P = .004), and cognitive impairment (P = .003). CONCLUSIONS: Functional and cognitive impairments are highly prevalent among older patients with PCa who receive androgen ablation in oncology clinics. The current results indicated that the brief VES-13 performed nearly as well as a conventional CGA in detecting geriatric impairment in this population.

Activities of Daily Living↗
PubMed2007

Health and motivation of elderly relocating to a suburban area in Japan.

In Japan, few studies have investigated the effects of moving residence among the elderly, despite the fact that Japanese elderly will be increasingly required to switch residence in the future. Here, we used representative sampling to examine the characteristics of elderly persons who had moved residence to a Tokyo suburb and compared results with those of non-moving residents of the suburb. Movers aged 65 years old or older who had relocated within the previous 2 years (movers) and residents aged 65 years old or older and had lived in the area longer than 5 years (non-movers) were surveyed by mail in 2004, with a focus on health and psychosocial measures. Compared with non-movers (N=117), movers (N=97) were more depressed, socially isolated, and fulfilled less active social roles among family members. The majority of movers had moved to find affordable housing or to live with or near family. Two factors preceded co-residence with family, namely retirement and imminent loss of functional independence. Our findings suggest that movers require community support to prevent social isolation, dependency and health declines.

Activities of Daily Living↗