ABSTRACT
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.
A phase II trial of huperzine A in mild to moderate Alzheimer disease, Neurology 2011;76: 1389–1394, M.S. Rafii,