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A phase II trial of huperzine A in mild to moderate Alzheimer disease

2011; Lippincott Williams & Wilkins; Volume: 76; Issue: 16 Linguagem: Inglês

10.1212/wnl.0b013e318216eb7b

1526-632X

Michael S. Rafii, Sally Walsh, John T. Little, K A Behan, Brigid Reynolds, Carwyn Ward, Shelia Jin, Ronald G. Thomas, Paul Aisen,

Health Systems, Economic Evaluations, Quality of Life

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 Alzheimer9s 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, Alzheimer9s Disease Cooperative Study–Clinical Global Impression of Change scale, Alzheimer9s 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.