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. Copyright Â
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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. Copyright Â
Authors: Bradley E Gray; Robert P McMahon; Michael F Green; Larry J Seidman; Raquelle I Mesholam-Gately; Robert S Kern; Keith H Nuechterlein; Richard S Keefe; James M Gold Journal: Schizophr Res Date: 2014-08-22 Impact factor: 4.939
Authors: Richard S E Keefe; Vicki G Davis; Philip D Harvey; Alexandra S Atkins; George M Haig; Owen Hagino; Stephen Marder; Dana C Hilt; Daniel Umbricht Journal: JAMA Psychiatry Date: 2017-08-01 Impact factor: 21.596
Authors: D Kimhy; O V Crowley; P S McKinley; M M Burg; M E Lachman; P A Tun; C D Ryff; T E Seeman; R P Sloan Journal: J Psychiatr Res Date: 2013-02-20 Impact factor: 4.791
Authors: L Fredrik Jarskog; Zhengchao Dong; Alayar Kangarlu; Tiziano Colibazzi; Ragy R Girgis; Lawrence S Kegeles; Deanna M Barch; Robert W Buchanan; John G Csernansky; Donald C Goff; Michael P Harms; Daniel C Javitt; Richard Se Keefe; Joseph P McEvoy; Robert P McMahon; Stephen R Marder; Bradley S Peterson; Jeffrey A Lieberman Journal: Neuropsychopharmacology Date: 2013-01-16 Impact factor: 7.853
Authors: Daniel Umbricht; Richard S E Keefe; Stephen Murray; David A Lowe; Richard Porter; George Garibaldi; Luca Santarelli Journal: Neuropsychopharmacology Date: 2014-01-27 Impact factor: 7.853