Evidence map›Paper›PMID 21502597›Full record

Trial reportNeurology2011

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, Alzheimer's Disease Cooperative Study

Open access · bronzeAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 12 pooled it
17.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 12 syntheses or guidelines pooled it, 227 citations in OpenAlex.

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  11. Huperzine A for mild cognitive impairment.The Cochrane database of systematic reviews · 2012
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  18. Perspectives from Alzheimer's Disease Research Centers site directors on the early steps and the lasting impact.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

M S RafiiDepartment of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, USA. mrafii@ucsd.edu
S Walsh
J T Little
K Behan
B Reynolds
C Ward
S Jin
R Thomas
P S Aisen
Alzheimer's Disease Cooperative Study
Georgetown University · US

Funding

RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
PSYCHOSOCIAL COREP30AG008051 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SHAO, YONGZHAO · 1990 to 2019
$36.1M
NIA NIH HHS P30 AG008051NIA NIH HHS U19 AG010483
6 · The paper itself

Abstract

objectiveHuperzine 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).

methodsWe 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).

resultsHuperzine 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.

conclusionThe 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.

Indexed as

AgedAged, 80 and overAlkaloidsAlzheimer DiseaseAnalysis of VarianceApolipoproteins EDose-Response Relationship, DrugDouble-Blind MethodFemaleFollow-Up StudiesHumansMaleMental Status ScheduleMiddle AgedNeuroprotective AgentsSesquiterpenesAlkaloidsApolipoproteins Ehuperzine ANeuroprotective AgentsSesquiterpenes

Identifiers

PMID21502597
PMCPMC3269774
OpenAlexW2049190733

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.