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Souvenaid is the name of a medical nutrition formulation, presented as a drink, that has been studied for potential use in the dietary management of early Alzheimer’s disease. Randomised controlled trials have shown that Souvenaid improves memory in subjects with early Alzheimer’s disease.

Souvenaid was developed by Advanced Medical Nutrition division of Nutricia and contains a patented combination of nutrients, referred to under the trademark Fortasyn Connect™. Souvenaid was designed to support synapse formation and function in early Alzheimer’s disease.

Development of Souvenaid concept
Souvenaid is the result of research by investigators from the Massachusetts Institute of Technology (MIT), and other international groups being conducted since 2002. Much of the research was led by MIT Professor Richard Wurtman.

The concept of Souvenaid is based on the fact that loss of synapses is one of the hallmarks of Alzheimer’s disease and that this hallmark correlates best with memory impairment. There is evidence in the scientific literature that individuals with this condition may lack adequate levels of nutrients important for the formation of new synapses in order to compensate for the experienced loss. Souvenaid has been studied in pre-clinical and clinical studies.

Pre-clinical Trials
Researchers demonstrated in pre-clinical models that by increasing the supply of certain nutrients, the synthesis of phospholipids and neuronal membranes can be increased. Those nutrients were also shown to increase dendritic spines, synaptic proteins and neurite outgrowth,  all prerequisites for synapse formation, as well as neurotransmission. The greatest effects were observed when combinations of nutrients were used. Administration of specific nutrients was also shown to improve learning and memory in preclinical models. These research findings provided the scientific rationale for the formulation of Souvenaid.

Early Alzheimer’s disease
Souvenaid has been tested in two randomised, controlled, double-blind clinical trials in early Alzheimer’s disease (AD). In both studies, Souvenaid was compared with a matched isocaloric, isonitrogenous control drink in mild AD subjects who had not received drug therapy for Alzheimer’s disease.

The ‘Souvenir I’ study included 225 subjects with mild Alzheimer’s disease (mean MMSE score 23.9) enrolled at sites in The Netherlands, Germany, Belgium, UK and USA. Results were published in 2010 in the journal Alzheimer’s & Dementia by Philip Scheltens and colleagues. The trial showed that daily Souvenaid for 12 weeks significantly improved the co-primary endpoint of delayed verbal memory, measured using the standard Wechsler Memory Scale-revised (WMS-r). There was no difference between Souvenaid and the control drink on the modified 13-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), the other co-primary endpoint.

The ‘Souvenir II’ study included 259 subjects with mild Alzheimer’s disease (mean MMSE score 25.0) enrolled in sites in The Netherlands, Germany, France, Belgium, Italy and Spain. Results were first presented by Philip Scheltens at the fourth congress ‘Clinical Trials on Alzheimer’s Disease (CtAD)’ in San Diego in November 2011. The study showed that during 24 weeks, Souvenaid significantly improved the predefined primary endpoint of memory, measured by the memory domain of a Neuropsychological Test Battery (NTB). No significant intervention effect was observed on the NTB executive function domain, a secondary endpoint of the study.

Souvenaid was well tolerated in both studies involving subjects with drug-naïve early Alzheimer’s disease. There was no difference in the incidence of adverse events between Souvenaid and the control drink. The trials were funded by Nutricia.

Mild-to-moderate Alzheimer’s disease
‘S-Connect’ was a 24-week randomised, controlled, double-blind study conducted in 48 centres in the USA in 527 subjects with mild-to-moderate Alzheimer’s disease (MMSE score 14–24). All subjects were on stable use of acetylcholinesterase inhibitors and/or N-methyl d-aspartate (NMDA) receptor antagonist. Results were first presented by Dr Raj Shah at the fourth congress ‘Clinical Trials on Alzheimer’s Disease (CtAD)’ in San Diego in November 2011. There was no difference in the primary efficacy endpoint of ADAS-cog between Souvenaid and control groups. No group differences in adverse event rates were seen between Souvenaid and the control drink. The trial was funded by Nutricia.

Prodromal Alzheimer’s disease
‘LipiDiDiet’ is a randomised, controlled trial conducted by the European LipiDiDiet Consortium and funded by the EU FP7 project LipiDiDiet, (Grant Agreement N° 211696). The study is designed to evaluate the effects of Souvenaid in subjects with prodromal Alzheimer’s disease defined by the Dubois criteria over a study period of 24 months. The primary endpoint is cognitive performance during 24 months of intervention as measured by a modified version of the NTB. Secondary endpoints include progression to Alzheimer’s disease, cognitive performance, functional abilities, occurrence of depressive symptoms, plasma biomarkers, brain atrophy rates on magnetic resonance imaging (MRI), nutritional parameters, tolerability and safety. As of May 2012, the study is still ongoing.