Dataset Information

Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease.

ABSTRACT:

Background

Currently available treatments for Alzheimer's disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD.

Methods

In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the 'last observation carried forward' approach, in an analysis of covariance model.

Results

In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (-2.14 [4.34]) compared with the galantamine group (-1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (-10.81 [18.27]) versus the galantamine group (-8.16 [17.25]) (P=0.002). Incidences of treatment-emergent adverse events were 54.0% for the galantamine and 48.6% for the placebo group.

Conclusion

Long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients.

Identification

This study is registered at ClinicalTrials.gov (NCT00679627).

SUBMITTER: Hager K

PROVIDER: S-EPMC3937252 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease.

Hager Klaus K Baseman Alan S AS Nye Jeffrey S JS Brashear H Robert HR Han John J Sano Mary M Davis Bonnie B Richards Henry M HM

Neuropsychiatric disease and treatment 20140221

<h4>Background</h4>Currently available treatments for Alzheimer's disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD.<h4>Methods</h4>In this multicenter, double-blind study, patients were randomized 1:1 to re ...[more]

PMID: 24591834

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Project description:Lucid dreaming is a remarkable state of consciousness in which one is aware of the fact that one is dreaming while continuing to dream. Based on the strong relationship between physiological activation during rapid eye-movement sleep and lucid dreaming, our pilot research investigated whether enhancing cortical activation via acetylcholinesterease inhibition (AChEI) would increase the frequency of lucid dreams and found AChEI to be a promising method for lucid dream induction. In the current study we sought to quantify the size and reliability of the effect of AChEI on lucid dreaming, dream recall and dream content as well as to test the effectiveness of an integrated lucid dream induction protocol which combined cholinergic stimulation with other methods for lucid dream induction. Participants (N = 121) with high dream recall and an interest in lucid dreaming were randomly assigned counterbalanced orders of 3 doses of galantamine (0, 4 and 8 mg). On 3 consecutive nights, they awoke approximately 4.5 hours after lights out, recalled a dream, ingested the capsules and stayed out of bed for at least 30 minutes. Participants then returned to bed and practiced the Mnemonic Induction of Lucid Dreams technique while returning to sleep. The percentage of participants who reported a lucid dream was significantly increased for both 4 mg (27%, odds ratio = 2.29) and 8 mg doses (42%, odds ratio = 4.46) compared to the active placebo procedure (14%). Galantamine also significantly increased dream recall, sensory vividness and complexity (p<0.05). Dream recall, cognitive clarity, control, positive emotion, vividness and self-reflection were increased during lucid compared to non-lucid dreams (p<0.0001). These results show that galantamine increases the frequency of lucid dreams in a dose-related manner. Furthermore, the integrated method of taking galantamine in the last third of the night with at least 30 minutes of sleep interruption and with an appropriately focused mental set is one of the most effective methods for inducing lucid dreams available today.

Project description:IntroductionCurcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD.MethodsWe performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex(®) with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured.ResultsMean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex(®) was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL).ConclusionsCurcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex(®) in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound.Trial registrationClinicalTrials.gov Identifier: NCT00099710.

Dataset Information

Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease.

Background

Methods

Results

Conclusion

Identification

Publications

Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease.

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