scholarly journals A Randomized, Controlled Trial of Linopirdine in the Treatment of Alzheimer's Disease

1997 ◽  
Vol 24 (2) ◽  
pp. 140-145 ◽  
Author(s):  
Kenneth Rockwood ◽  
B. Lynn Beattie ◽  
M. Robin Eastwood ◽  
Howard Feldman ◽  
Erich Mohr ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Controlled Trial ◽  
Small Degree ◽  
Disease Assessment ◽  
Double Blind ◽  
Cognitive Subscale ◽  
Parallel Group ◽  
Treatment Dose ◽  
Age Range

ABSTRACT:Objectives:We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease.Methods:A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline.Results:No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01.Conclusions:This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

scholarly journals A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shifu Xiao ◽  
Piu Chan ◽  
Tao Wang ◽  
Zhen Hong ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Controlled Trial ◽  
Drug Effects ◽  
Disease Assessment ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

Acetyl L-Carnitine Slows Decline in Younger Patients With Alzheimer's Disease: A Reanalysis of a Double-Blind, Placebo-Controlled Study Using the Trilinear Approach

1998 ◽  
Vol 10 (2) ◽  
pp. 193-203 ◽  
Author(s):  
John O. Brooks ◽  
Jerome A. Yesavage ◽  
Angelico Carta ◽  
Daniele Bravi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Average Rate ◽  
The United States ◽  
Rate Of Change ◽  
Disease Assessment ◽  
Controlled Study ◽  
Double Blind ◽  
Parallel Group ◽  
Longitudinal Effects

Objectives: To assess the longitudinal effects of acetyl-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease. Design: Longitudinal, double-blind, parallel-group, placebocontrolled. Setting: Twenty-four outpatient sites across the United States. Participants: A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996). Measurements: Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year. Results: The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age × Drug interaction characterized by younger subjects benefiting more from ALC treatment than older subjects. Further analyses suggested that the optimal, though not statistically significant, cutpoint for ALC benefit was 61 years of age. Conclusions: ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.

scholarly journals A 36-week Multicenter, Randomised, Double-blind, Placebo-controlled, Parallel-group, Phase 3 Clinical Trial of Sodium Oligomannate for Mild-to-Moderate Alzheimer's Dementia

2020 ◽  
Author(s):  
Shifu Xiao ◽  
Piu Chan ◽  
Tao Wang ◽  
Zhen Hong ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Controlled Trial ◽  
Drug Effects ◽  
Disease Assessment ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Difference

Abstract Background: New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide which reconstitutes gut microbiota, reduces neuroinflammation, decreases amyloid deposition, and improves cognition in AD animal models. The first phase 3 clinical trial of GV-971 has been completed in China. Methods: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results: 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time-point, measurable at the week 4 visit and continuing throughout the trial. The difference between groups in change from baseline was −2.15 points (95% confidence interval, −3.07 to −1.23; P<0.0001; effect size 0.531) after 36 weeks treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group.Conclusions: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well tolerated. Trial registration: ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014.

scholarly journals Effectiveness and Safety of MLC601 in the Treatment of Mild to Moderate Alzheimer's Disease: A Multicenter, Randomized Controlled Trial

2015 ◽  
Vol 5 (1) ◽  
pp. 96-106 ◽  
Author(s):  
Hossein Pakdaman ◽  
Ali Amini Harandi ◽  
Hamidreza Hatamian ◽  
Mojgan Tabatabae ◽  
Hosein Delavar Kasmaei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Diagnostic Interview ◽  
Disease Assessment ◽  
Amyloid Precursor Protein Processing ◽  
Randomized Controlled ◽  
Cognitive Subscale ◽  
Multicenter Randomized Controlled Trial

Background: MLC601 is a possible modulator of amyloid precursor protein processing, and in a clinical trial study MLC601 showed some effectiveness in cognitive function in Alzheimer's disease (AD) patients. We aimed to evaluate the effectiveness and safety of MLC601 in the treatment of mild to moderate AD as compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine and galantamine. Methods: In a multicenter, nonblinded, randomized controlled trial, 264 volunteers with AD were randomly divided into 4 groups of 66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and galantamine, respectively. Subjects underwent a clinical diagnostic interview and a cognitive/functional battery including the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog). Patients were visited every 4 months, and the score of cognition was recorded by the neurologists. Results: There were no significant differences in age, sex, marital status and baseline score of cognition among the 4 groups. In total, 39 patients (14.7%) left the study. Trend of cognition changes based on the modifications over the time for MMSE and ADAS-cog scores did not differ significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog). Conclusion: MLC601 showed a promising safety profile and also efficacy compared to 3 FDA-approved ChEIs.

The Effect of Memantine on Cognitive Function and Behavioral and Psychological Symptoms in Mild-to-Moderate Alzheimer's Disease Patients

2015 ◽  
Vol 40 (1-2) ◽  
pp. 85-93 ◽  
Author(s):  
Nan Zhang ◽  
Changjuan Wei ◽  
Hongjian Du ◽  
Fu-Dong Shi ◽  
Yan Cheng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Psychological Symptoms ◽  
Disease Assessment ◽  
Control Treatment ◽  
Double Blind ◽  
Treatment Groups ◽  
Cognitive Subscale ◽  
Double Blind Clinical Trial ◽  
Post Hoc

Background/Aims: Memantine has been approved by the Food and Drug Administration for the treatment of moderate-to-severe Alzheimer's disease (AD). However, the effect of memantine on patients with mild-to-moderate AD is unclear. Methods: This study is a post hoc analysis of a double-blind clinical trial. Donepezil was used as the standard control treatment. Outcomes included score changes from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), a modified 20-item Activities of Daily Living Scale (ADL), the Neuropsychiatric Inventory (NPI), and the Mini-Mental State Examination (MMSE) as well as the score of the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-Plus). Results: One hundred sixty-seven AD patients with an MMSE score of 10-24 were analyzed. No significant differences in the score changes from baseline to week 24 on all outcomes or the four subscales of the ADAS-cog were observed between the two treatment groups. Donepezil resulted in an improved score for naming ability on the ADAS-cog compared to memantine (p = 0.036), whereas memantine more effectively reduced agitation as measured by the NPI compared to donepezil (p = 0.039). Conclusion: These findings support the efficacy of memantine for the treatment of mild-to-moderate AD, especially in patients with agitation.

Attenuation in the Progression of Cognitive Deterioration in Alzheimer's Disease With Rivastigmine: A Dose-Dependent Effect

CNS Spectrums ◽  
2000 ◽  
Vol 5 (6) ◽  
pp. 21-22 ◽  
Author(s):  
Martin Farlow ◽  
John Messina ◽  
Ravi Anand ◽  
Richard Hartman ◽  
Jeffrey Veach
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Controlled Trial ◽  
Weighted Least Squares ◽  
Disease Assessment ◽  
Cognitive Deterioration ◽  
Attrition Rates ◽  
Cognitive Subscale ◽  
Rate Of Decline

AbstractObjectives: Possible disease-modifying effects of rivastigmine have been suggested by analyses using a variation of the randomized start design; however, the results were somewhat confounded by differing attrition rates. We report on an alternative method investigating whether increasing doses reduce the rates of cognitive decline in patients who continue treatment.Methods: The effect of dose on the rate of cognitive decline seen on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was explored for patients in a long-term (130-week) extension of a 26-week placebo-controlled trial using two methods: a weighted leas squares regression analysis using each individual's slope, and a weighted analysis of variance (ANOVA) comparing the slopes of patients categorized by dose (≤6 mg/d or >6 mg/d).Results: The results from 408 patients included in the weighted least squares analysis estimated the rate of decline to attenuate by approximately 1 point/y for every 3 mg/d increase (P<.0001). The average annual rate of decline for patients whose mean dose was >6 mg/d was 4.5 points (95% Cl, 5.1–3.9), while for patients with a mean dose of≥6 mg/d a decline of 8.2 points (95% Cl, 9.1–7.3) was seen.Conclusion: These data further support earlier results suggesting that rivastigmine reduces the rate of progression of cognitive deterioration in Alzheimer's disease.

scholarly journals NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

BMJ Open ◽  
2014 ◽  
Vol 4 (10) ◽  
pp. e006364 ◽  
Author(s):  
Brian Lawlor ◽  
Sean Kennelly ◽  
Sarah O'Dwyer ◽  
Fiona Cregg ◽  
Cathal Walsh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Controlled Trial ◽  
Phase Iii ◽  
Disease Assessment ◽  
Secondary Outcome ◽  
Outcome Analysis ◽  
Double Blind ◽  
Double Blind Placebo

IntroductionThis study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks.Methods and analysisAdult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis.Ethics and disseminationThe study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal.Trial registration numberEUDRACT Reference Number: 2012-002764-27.

Validation of the Hungarian version of Alzheimer’s Disease Assessment Scale – Cognitive Subscale

2012 ◽  
Vol 153 (12) ◽  
pp. 461-466 ◽  
Author(s):  
Magdolna Pákáski ◽  
Gergely Drótos ◽  
Zoltán Janka ◽  
János Kálmán
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mental State ◽  
Mini Mental State Examination ◽  
Assessment Scale ◽  
Disease Assessment ◽  
Control Subjects ◽  
Cognitive Subscale ◽  
State Examination ◽  
Hungarian Version

The cognitive subscale of the Alzheimer’s Disease Assessment Scale is the most widely used test in the diagnostic and research work of Alzheimer’s disease. Aims: The aim of this study was to validate and investigate reliability of the Hungarian version of the Alzheimer’s Disease Assessment Scale in patients with Alzheimer’s disease and healthy control subjects. Methods: syxty-six patients with mild and moderate Alzheimer’s disease and 47 non-demented control subjects were recruited for the study. The cognitive status was established by the Hungarian version of the Alzheimer’s Disease Assessment Scale and Mini Mental State Examination. Discriminative validity, the relation between age and education and Alzheimer’s Disease Assessment Scale, and the sensitivity and specificity of the test were determined. Results: Both the Mini Mental State Examination and the Alzheimer’s Disease Assessment Scale had significant potential in differentiating between patients with mild and moderate stages of Alzheimer’s disease and control subjects. A very strong negative correlation was established between the scores of the Mini Mental State Examination and the Alzheimer’s Disease Assessment Scale in the Alzheimer’s disease group. The Alzheimer’s Disease Assessment Scale showed slightly negative relationship between education and cognitive performance, whereas a positive correlation between age and Alzheimer’s Disease Assessment Scale scores was detected only in the control group. According to the analysis of the ROC curve, the values of sensitivity and specificity of the Alzheimer’s Disease Assessment Scale were high. Conclusions: The Hungarian version of the Alzheimer’s Disease Assessment Scale was found to be highly reliable and valid and, therefore, the application of this scale can be recommended for the establishment of the clinical stage and follow-up of patients with Alzheimer’s disease. However, the current Hungarian version of the Alzheimer’s Disease Assessment Scale is not sufficient; the list of words and linguistic elements should be selected according to the Hungarian standard in the future. Orv. Hetil., 2012, 153, 461–466.

scholarly journals Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soo Hyun Cho ◽  
Sookyoung Woo ◽  
Changsoo Kim ◽  
Hee Jin Kim ◽  
Hyemin Jang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Assessment ◽  
Time Interval ◽  
Disease Course ◽  
Preclinical Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
Preclinical Ad ◽  
Cognitive Subscale

AbstractTo characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

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