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P1‐279: NIC5‐15 as a treatment for Alzheimer's: Safety, pharmacokinetics and clinical variables
Author(s) -
Grossman Hillel,
Marzloff George,
Luo Xiaodong,
LeRoith Derek,
Sano Mary,
Pasinetti Giulio
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.287
Subject(s) - tolerability , pharmacokinetics , placebo , medicine , adverse effect , pharmacodynamics , pharmacology , clinical trial , vital signs , anesthesia , alternative medicine , pathology
Background: Many epidemiological studies indicate a clear link between nutrition and Alzheimer’s Disease (AD). Several nutrient deficiencies have been shown to be risk factors for AD. Prospective studies with nutrients, like omega-3 fatty acids or the Mediterranean diet, show a reduced risk of developing AD. Preclinical studies have shown that combinations of specific nutrients synergistically increased membrane and synapse formation, diagnostic features that have been demonstrated to be reduced in AD, resulting in improved learning behavior in animal models. In addition, this specific combination reduces abeta production, plaque burden and neurodegeneration in transgenic mice. Methods: The effect of a medical food (Souvenaid ), designed to improve synapse formation, on memory and cognitive performance was assessed in a proof-of-concept trial with drug naı̈ve mild AD patients. AD patients (MMSE 20-26) were randomly allocated to Souvenaid , a 125 mL (125 kcal) once-a-day milk-based drink or an iso-caloric control drink in a double-blind 12-week study. Primary outcome parameters were a delayed verbal memory task (Wechsler Memory Scalerevised) and the 13-item ADAS-cog, assessed at 12 weeks. In an optional double-blind 12week extension phase patients continued to receive the same study product. The trial is registered with the Dutch Trial Register (#ISRCTN72254645). Results: 212 patients were included in the primary efficacy analysis (mean MMSE 23.9; mean age 73.7; 50% men). Delayed verbal memory, analysed by non-parametric statistics, was significantly improved in the Souvenaid group. In the statistical model excluding covariates no suggestion for an effect was found for 13-item ADAS-cog. There was no significant difference in tolerance (94% compliance) and (serious) adverse events between the study groups throughout the study period. To confirm and further strengthen the results of this first study 2 additional trials with Souvenaid are designed and will start in 2009: EU study, a 24-week study in drug naı̈ve mild AD patients. US study (S-Connect), a 24-week study in mild-to-moderate AD patients using AD medication. Conclusions: Souvenaid has a good safety and tolerability profile, and improves memory in mild AD. These promising results justify further studies in AD. Two clinical trials testing Souvenaid in mild-to-moderate Alzheimer’s patients will start in 2009.