title: Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia.
abstract: BACKGROUND
  Cognitive dysfunction is a key predictor of functional disability in schizophrenia. Davunetide (AL-108, NAP) is an intranasally administered peptide currently being developed for treatment of Alzheimer's disease and related disorders. This study investigates effects of davunetide on cognition in schizophrenia.
  
  
  METHODS
  Sixty-three subjects with schizophrenia received davunetide at one of two different doses (5, 30 mg) or placebo for 12 weeks in a multicenter, double-blind, parallel-group randomized clinical trial. The MATRICS Consensus Cognitive Battery (MCCB) assessed cognitive effects. The UCSD Performance-based Skills Assessment (UPSA) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. Subjects continued their current antipsychotic treatment during the trial.
  
  
  RESULTS
  There were no significant differences in MCCB change between davunetide and placebo over the three treatment arms (p=.45). Estimated effect-size (d) values were .34 and .21 favoring the 5 and 30 mg doses vs. placebo, respectively. For UPSA, there was a significant main effect of treatment across study arms (p=.048). Between-group effect size (d) values were.74 and .48, favoring the 5 and 30 mg doses, respectively. No significant effects were observed on the SCoRS or on symptom ratings. No significant side effects or adverse events were observed.
  
  
  CONCLUSIONS
  Davunetide was well tolerated. Effects of davunetide on MCCB-rated cognition were not significant relative to placebo. In contrast, a significant beneficial effect was detected for the UPSA. Based upon effect-size considerations, sample sizes of at least 45-50 subjects/group would be required to obtain significant effects on both MCCB and UPSA, providing guidance for continued clinical development in schizophrenia.
authors.affiliation: Nathan Kline Institute for Psychiatry Research, Orangeburg, NY, United States. javitt@nki.rfmh.org
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Javitt
authors.forename: Robert W
authors.initials: RW
authors.lastname: Buchanan
authors.forename: Richard S E
authors.initials: RS
authors.lastname: Keefe
authors.forename: Robert
authors.initials: R
authors.lastname: Kern
authors.forename: Robert P
authors.initials: RP
authors.lastname: McMahon
authors.forename: Michael F
authors.initials: MF
authors.lastname: Green
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lieberman
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.forename: John G
authors.initials: JG
authors.lastname: Csernansky
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: Fred
authors.initials: F
authors.lastname: Jarskog
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: James M
authors.initials: JM
authors.lastname: Gold
authors.forename: David
authors.initials: D
authors.lastname: Kimhy
authors.forename: Karen S
authors.initials: KS
authors.lastname: Nolan
authors.forename: Deanna S
authors.initials: DS
authors.lastname: Barch
authors.forename: M Patricia
authors.initials: MP
authors.lastname: Ball
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Marder
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001288:Attention / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D009842:Oligopeptides / Q000627:therapeutic use*; D011340:Problem Solving / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications*; D012565:Schizophrenic Psychology; D014706:Verbal Learning / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D009842:Oligopeptides; C425904:davunetide