Huperzine A is a multicenter, double-blind, placebo-controlled therapeutic trial to determine whether natural huperzine A improves cognitive function in Alzheimer’s Disease

Project Director

Paul Aisen, MD

Background and Significance

Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata. There is evidence that huperzine A may compare favorably in symptomatic efficacy to cholinesterase inhibitors currently in use. In addition, huperzine A has antioxidant and neuroprotective properties that suggest that it may be useful as a disease-modifying treatment for Alzheimer’s disease (AD). The drug is currently available as a nutriceutical in this country, and is being used by some U.S. clinicians to treat AD. However, there have been no controlled clinical trials outside China assessing its toxicity and efficacy.

Primary Objective

The primary objective is to demonstrate in a randomized, placebo-controlled trial whether treatment with huperzine A 200 micrograms twice daily improves cognitive function in patients with AD over a period of 24 weeks.

Secondary Objectives

The chief secondary aim includes determining whether treatment with huperzine A 400 micrograms improves cognitive function in patients with AD. We assessed the effect of huperzine A treatment on global clinical status, activities of daily living, and beavior in AD. We evaluated the tolerability of huperzine A treatment at dosages of 200 microgram twice daily and 400 microgram twice daily in AD. We studied the relationship between blood cholinesterase activity and cognitive function in AD patients treated with huperzine A.

Study Design

This was a randomized, double-blind, placebo-controlled study. Participants were randomly assigned to three equal groups of huperzine A 200 microgram bid, 400 microgram twice daily, and placebo.

Study Size

150 participants were enrolled at approximately 20 sites.

Subject Selection Criteria

The selection process was designed to allow enrollment of all AD individuals likely to be testable at the conclusion of the study period. The study targeted those with an MMSE of 10-24 inclusive and includes women and members of minority groups.

Statistical Measures

The primary analysis was conducted on an intent-to-treat basis. It is a comparison of the week 16 ADAS-Cog score between each active group and placebo using analysis of covariance (ANCOVA), with the baseline ADAScog score as a covariate.