An open label extension study to evaluate long term use of a Food for Special Medical Purposes (FSMP) in patients with mild Alzheimer*s disease
who completed the Souvenir II study

The protocol describes an open label extension study for those subjects
completing the randomised controlled double-blind Souvenir II study or Souvenir
II MEG sub-study.

The Souvenir II study was developed to confirm and extend the results of the
12-week double-blind controlled Souvenir study with a similarly designed
12-week extension period. The Souvenir study demonstrated that the
multi-nutrient study product *Souvenaid®* improved 12-week memory performance
both in the overall ITT (baseline MMSE 20-26, n=225) population and in the
prespecified subgroup analysis of patients with very mild Alzheimer*s Disesase
(AD). Furthermore, the Souvenir study showed that Souvenaid has a good safety
profile and was well tolerated throughout 24 weeks of supplementation [1]. In
the currently running Souvenir II study and Souvenir II MEG sub-study, a
similar study population of mild to very mild AD patients (MMSE >= 20) with no
current use of AD medication is included, and memory performance is again the
primary outcome.

The purpose of this open label extension study is to gather further compliance
and safety information on the longer-term (up to approximately 48 weeks) use of
the study product. This will provide valuable information in addition to the
findings of the so far conducted [1] and running studies (Souvenir II; NTR1975,
and the S-Connect study; NTR1683) with Souvenaid which have a maximum
intervention duration of approximately 24 weeks. Furthermore, the intention of
the 24-week open label extension study is to provide ongoing medical nutrition
therapy for subjects who completed the Souvenir II study.

A 24-week multicentre multi-country open label extension study.

The study product is a 125ml (125kcal) once-a-day drink to be taken with
breakfast. There is a choice of two flavours: vanilla and strawberry.

From a proof of concept study in 225 AD subjects with the same study product,
it has been concluded that the study product has a good safety profile and is
well tolerated throughout 24 weeks of supplementation. Of the procedures,
venepuncture for collecting blood samples might cause bruising.
Three study visits are scheduled, the first of which is combined with the week
24 visit of the Souvenir II study or the Souvenir II MEG sub-study. For this
first visit the data of the Souvenir II study or Souvenir II MEG sub-study week
24 visit is used for baseline data. For the Open Label Extension study the
mental state is noted using the MMSE. During the second (week 12) study visit
cognition is assessed through the memory domain z-score of the
Neuropsychological Test Battery (NTB)). This is done again during the third and
final visit. Furthermore a product evaluation questionnaire is completed, vital
signs and weight are measured, and a blood sample is taken. During all visits,
and during the telephone contacts at week 6, 18, and 2 week follow up, the
overall health, occurrence of (S)AEs and changes in concomitant medication are
required after and noted.