Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2011 Apr 19;76(16):1389-94.
doi: 10.1212/WNL.0b013e318216eb7b.

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

M S Rafii  1 , S Walsh, J T Little, K Behan, B Reynolds, C Ward, S Jin, R Thomas, P S Aisen; Alzheimer's Disease Cooperative Study
Collaborators, Affiliations
Clinical Trial

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

M S Rafii et al. Neurology. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Participant flow through the phase II huperzine A trial
A total of 287 subjects were screened for the trial, and 210 were eligible and randomized. The most common reason for screen failure was Mini-Mental State Examination score being too high.
Figure 2
Figure 2. Intention-to-treat last observation carried forward analyses of Alzheimer's Disease Assessment Scale–cognitive subscale (ADAS-Cog) change score
Placebo n = 69, 200 μg n = 68, 400 μg n = 73.
See this image and copyright information in PMC

References

    1. Wang YE, Yue DX, Tang XC. [Anti-cholinesterase activity of huperzine A.] Chung Kuo Yao Li Hsueh Pao 1986;7:110–113 - PubMed
    1. Ashani Y, Peggins JO, Doctor BP. Mechanism of inhibition of cholinesterases by huperzine A. Biochem Biophys Res Commun 1992;184:719–726 - PubMed
    1. Saxena A, Qian N, Kovach IM, et al. Identification of amino acid residues involved in the binding of huperzine A to cholinesterases. Protein Sci 1994;3:1770–1778 - PMC - PubMed
    1. Camps P, Muñoz-Torrero D. Tacrine-huperzine A hybrids (huprines): a new class of highly potent and selective acetylcholinesterase inhibitors of interest for the treatment of Alzheimer's disease. Mini Rev Med Chem 2001;1:163–174 - PubMed
    1. Wang R, Yan H, Tang XC. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin 2006;27:1–26 - PubMed

Publication types