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

M. S. Rafii, S. Walsh, J. T. Little, K. Behan, B. Reynolds, C. Ward, S. Jin, R. Thomas, P. S. Aisen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1389-1394
Number of pages6
JournalNeurology
Volume76
Issue number16
DOIs
StatePublished - Apr 19 2011
Externally publishedYes

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Alzheimer Disease
Placebos
Cholinesterase Inhibitors
Activities of Daily Living
Huperzia
huperzine A
Equipment and Supplies
Multicenter Studies
Safety

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Rafii, M. S., Walsh, S., Little, J. T., Behan, K., Reynolds, B., Ward, C., ... Aisen, P. S. (2011). A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology, 76(16), 1389-1394. https://doi.org/10.1212/WNL.0b013e318216eb7b

A phase II trial of huperzine A in mild to moderate Alzheimer disease. / Rafii, M. S.; Walsh, S.; Little, J. T.; Behan, K.; Reynolds, B.; Ward, C.; Jin, S.; Thomas, R.; Aisen, P. S.

In: Neurology, Vol. 76, No. 16, 19.04.2011, p. 1389-1394.

Research output: Contribution to journalArticle

Rafii, MS, Walsh, S, Little, JT, Behan, K, Reynolds, B, Ward, C, Jin, S, Thomas, R & Aisen, PS 2011, 'A phase II trial of huperzine A in mild to moderate Alzheimer disease', Neurology, vol. 76, no. 16, pp. 1389-1394. https://doi.org/10.1212/WNL.0b013e318216eb7b
Rafii MS, Walsh S, Little JT, Behan K, Reynolds B, Ward C et al. A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology. 2011 Apr 19;76(16):1389-1394. https://doi.org/10.1212/WNL.0b013e318216eb7b
Rafii, M. S. ; Walsh, S. ; Little, J. T. ; Behan, K. ; Reynolds, B. ; Ward, C. ; Jin, S. ; Thomas, R. ; Aisen, P. S. / A phase II trial of huperzine A in mild to moderate Alzheimer disease. In: Neurology. 2011 ; Vol. 76, No. 16. pp. 1389-1394.
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AU - Walsh, S.

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AU - Reynolds, B.

AU - Ward, C.

AU - Jin, S.

AU - Thomas, R.

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N2 - 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.

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