Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia.
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. METHOD: 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. CONCLUSION: 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.
Javitt, DC; Buchanan, RW; Keefe, RSE; Kern, R; McMahon, RP; Green, MF; Lieberman, J; Goff, DC; Csernansky, JG; McEvoy, JP; Jarskog, F; Seidman, LJ; Gold, JM; Kimhy, D; Nolan, KS; Barch, DS; Ball, MP; Robinson, J; Marder, SR
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