Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia

Daniel C. Javitt, Robert W. Buchanan, Richard S.E. Keefe, Robert Kern, Robert P. McMahon, Michael F. Green, Jeffrey Lieberman, Donald C. Goff, John G. Csernansky, Joseph Patrick McEvoy, Fred Jarskog, Larry J. Seidman, James M. Gold, David Kimhy, Karen S. Nolan, Deanna S. Barch, M. Patricia Ball, James Robinson, Stephen R. Marder

Research output: Contribution to journalArticle

75 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalSchizophrenia Research
Volume136
Issue number1-3
DOIs
StatePublished - Apr 1 2012

Fingerprint

Cognition
Schizophrenia
Peptides
Consensus
Placebos
Therapeutics
davunetide
Sample Size
Antipsychotic Agents
Alzheimer Disease
Randomized Controlled Trials

Keywords

  • Cognition
  • Microtubule
  • Neurite
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Javitt, D. C., Buchanan, R. W., Keefe, R. S. E., Kern, R., McMahon, R. P., Green, M. F., ... Marder, S. R. (2012). Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia. Schizophrenia Research, 136(1-3), 25-31. https://doi.org/10.1016/j.schres.2011.11.001

Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia. / Javitt, Daniel C.; Buchanan, Robert W.; Keefe, Richard S.E.; Kern, Robert; McMahon, Robert P.; Green, Michael F.; Lieberman, Jeffrey; Goff, Donald C.; Csernansky, John G.; McEvoy, Joseph Patrick; Jarskog, Fred; Seidman, Larry J.; Gold, James M.; Kimhy, David; Nolan, Karen S.; Barch, Deanna S.; Ball, M. Patricia; Robinson, James; Marder, Stephen R.

In: Schizophrenia Research, Vol. 136, No. 1-3, 01.04.2012, p. 25-31.

Research output: Contribution to journalArticle

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 2012, 'Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia', Schizophrenia Research, vol. 136, no. 1-3, pp. 25-31. https://doi.org/10.1016/j.schres.2011.11.001
Javitt, Daniel C. ; Buchanan, Robert W. ; Keefe, Richard S.E. ; Kern, Robert ; McMahon, Robert P. ; Green, Michael F. ; Lieberman, Jeffrey ; Goff, Donald C. ; Csernansky, John G. ; McEvoy, Joseph Patrick ; Jarskog, Fred ; Seidman, Larry J. ; Gold, James M. ; Kimhy, David ; Nolan, Karen S. ; Barch, Deanna S. ; Ball, M. Patricia ; Robinson, James ; Marder, Stephen R. / Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia. In: Schizophrenia Research. 2012 ; Vol. 136, No. 1-3. pp. 25-31.
@article{bf28d23389ea47868d75eaaab26dc0fb,
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. 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.",
keywords = "Cognition, Microtubule, Neurite, Schizophrenia",
author = "Javitt, {Daniel C.} and Buchanan, {Robert W.} and Keefe, {Richard S.E.} and Robert Kern and McMahon, {Robert P.} and Green, {Michael F.} and Jeffrey Lieberman and Goff, {Donald C.} and Csernansky, {John G.} and McEvoy, {Joseph Patrick} and Fred Jarskog and Seidman, {Larry J.} and Gold, {James M.} and David Kimhy and Nolan, {Karen S.} and Barch, {Deanna S.} and Ball, {M. Patricia} and James Robinson and Marder, {Stephen R.}",
year = "2012",
month = "4",
day = "1",
doi = "10.1016/j.schres.2011.11.001",
language = "English (US)",
volume = "136",
pages = "25--31",
journal = "Schizophrenia Research",
issn = "0920-9964",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia

AU - Javitt, Daniel C.

AU - Buchanan, Robert W.

AU - Keefe, Richard S.E.

AU - Kern, Robert

AU - McMahon, Robert P.

AU - Green, Michael F.

AU - Lieberman, Jeffrey

AU - Goff, Donald C.

AU - Csernansky, John G.

AU - McEvoy, Joseph Patrick

AU - Jarskog, Fred

AU - Seidman, Larry J.

AU - Gold, James M.

AU - Kimhy, David

AU - Nolan, Karen S.

AU - Barch, Deanna S.

AU - Ball, M. Patricia

AU - Robinson, James

AU - Marder, Stephen R.

PY - 2012/4/1

Y1 - 2012/4/1

N2 - 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.

AB - 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.

KW - Cognition

KW - Microtubule

KW - Neurite

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=84857997678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857997678&partnerID=8YFLogxK

U2 - 10.1016/j.schres.2011.11.001

DO - 10.1016/j.schres.2011.11.001

M3 - Article

VL - 136

SP - 25

EP - 31

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

IS - 1-3

ER -