OBJECTIVE:Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata that may compare favorably in symptomatic efficacy to cholinesterase inhibitors currently in use for Alzheimer disease (AD). METHODS: We assessed the safety, tolerability, and efficacy of huperzine A in mild to moderate AD in a multicenter trial in which 210 individuals were randomized to receive placebo (n = 70) or huperzine A (200 μg BID [n = 70] or 400 μg BID [n = 70]), for at least 16 weeks, with 177 subjects completing the treatment phase. The primary analysis assessed the cognitive effects of huperzine A 200 μg BID (change in Alzheimer's Disease Assessment Scale-cognitive subscale [ADAS-Cog] at week 16 at 200 μg BID compared to placebo). Secondary analyses assessed the effect of huperzine A 400 μg BID, as well as effect on other outcomes including Mini-Mental State Examination, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change scale, Alzheimer's Disease Cooperative Study Activities of Daily Living scale, and Neuropsychiatric Inventory (NPI). RESULTS:Huperzine A 200 μg BID did not influence change in ADAS-Cog at 16 weeks. In secondary analyses, huperzine A 400 μg BID showed a 2.27-point improvement in ADAS-Cog at 11 weeks vs 0.29-point decline in the placebo group (p = 0.001), and a 1.92-point improvement vs 0.34-point improvement in the placebo arm (p = 0.07) at week 16. Changes in clinical global impression of change, NPI, and activities of daily living were not significant at either dose. CONCLUSION: The primary efficacy analysis did not show cognitive benefit with huperzine A 200 μg BID. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that huperzine A 200 μg BID has no demonstrable cognitive effect in patients with mild to moderate AD.
RCT Entities:
OBJECTIVE:Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata that may compare favorably in symptomatic efficacy to cholinesterase inhibitors currently in use for Alzheimer disease (AD). METHODS: We assessed the safety, tolerability, and efficacy of huperzine A in mild to moderate AD in a multicenter trial in which 210 individuals were randomized to receive placebo (n = 70) or huperzine A (200 μg BID [n = 70] or 400 μg BID [n = 70]), for at least 16 weeks, with 177 subjects completing the treatment phase. The primary analysis assessed the cognitive effects of huperzine A 200 μg BID (change in Alzheimer's Disease Assessment Scale-cognitive subscale [ADAS-Cog] at week 16 at 200 μg BID compared to placebo). Secondary analyses assessed the effect of huperzine A 400 μg BID, as well as effect on other outcomes including Mini-Mental State Examination, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change scale, Alzheimer's Disease Cooperative Study Activities of Daily Living scale, and Neuropsychiatric Inventory (NPI). RESULTS:Huperzine A 200 μg BID did not influence change in ADAS-Cog at 16 weeks. In secondary analyses, huperzine A 400 μg BID showed a 2.27-point improvement in ADAS-Cog at 11 weeks vs 0.29-point decline in the placebo group (p = 0.001), and a 1.92-point improvement vs 0.34-point improvement in the placebo arm (p = 0.07) at week 16. Changes in clinical global impression of change, NPI, and activities of daily living were not significant at either dose. CONCLUSION: The primary efficacy analysis did not show cognitive benefit with huperzine A 200 μg BID. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that huperzine A 200 μg BID has no demonstrable cognitive effect in patients with mild to moderate AD.
Authors: P S Aisen; K L Davis; J D Berg; K Schafer; K Campbell; R G Thomas; M F Weiner; M R Farlow; M Sano; M Grundman; L J Thal Journal: Neurology Date: 2000-02-08 Impact factor: 9.910
Authors: Paul S Aisen; Lon S Schneider; Mary Sano; Ramon Diaz-Arrastia; Christopher H van Dyck; Myron F Weiner; Teodoro Bottiglieri; Shelia Jin; Karen T Stokes; Ronald G Thomas; Leon J Thal Journal: JAMA Date: 2008-10-15 Impact factor: 56.272
Authors: A Saxena; N Qian; I M Kovach; A P Kozikowski; Y P Pang; D C Vellom; Z Radić; D Quinn; P Taylor; B P Doctor Journal: Protein Sci Date: 1994-10 Impact factor: 6.725
Authors: Dou Yu; Devang K Thakor; Inbo Han; Alexander E Ropper; Hariprakash Haragopal; Richard L Sidman; Ross Zafonte; Steven C Schachter; Yang D Teng Journal: Proc Natl Acad Sci U S A Date: 2013-02-05 Impact factor: 11.205