title: Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.
abstract: BACKGROUND
  The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs.
  
  
  OBJECTIVE
  In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated.
  
  
  METHODS
  Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter.
  
  
  RESULTS
  Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention.
  
  
  CONCLUSIONS
  Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.
authors.affiliation: Radboud Alzheimer Centre, Department of Geriatric Medicine, Radboud University Hospital, Nijmegen, The Netherlands.
authors.forename: Marcel G M
authors.initials: MG
authors.lastname: Olde Rikkert
authors.affiliation: Alzheimer Centre Limburg, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Frans R
authors.initials: FR
authors.lastname: Verhey
authors.affiliation: Department of Neurology, Hospital de la Sta Creu i St. Pau, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Christine A F
authors.initials: CA
authors.lastname: von Arnim
authors.affiliation: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Bongers
authors.affiliation: Metis Cognition Ltd, Kilmington, UK & Imperial College, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Harrison
authors.affiliation: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: Sijben
authors.affiliation: University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.affiliation: University Department of Geriatrics, Antwerp Hospital Network (ZNA St Elisabeth), University of Antwerp, Belgium.
authors.forename: Maurits F J
authors.initials: MF
authors.lastname: Vandewoude
authors.affiliation: Gerontopole, INSERM U 1027, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Renger
authors.initials: R
authors.lastname: Witkamp
authors.affiliation: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands.
authors.forename: Patrick J G H
authors.initials: PJ
authors.lastname: Kamphuis
authors.affiliation: Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D001628:Beverages / Q000009:adverse effects; D004281:Docosahexaenoic Acids / Q000097:blood; D004311:Double-Blind Method; D004912:Erythrocytes / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005526:Food, Formulated / Q000009:adverse effects; D006801:Humans; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D010349:Patient Compliance; D016896:Treatment Outcome; D014810:Vitamin E / Q000097:blood
chemical_list: D005227:Fatty Acids; D018697:Nootropic Agents; D014810:Vitamin E; D004281:Docosahexaenoic Acids
keywords: Alzheimer's disease; clinical trial; dietary management; intervention studies; long-term; medical nutrition therapy; memory; patient adherence; safety