Evidence map›Paper›PMID 24696507›Full record

Trial reportNeurology2014

Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease.

Douglas Galasko, Joanne Bell, Jessica Y Mancuso, James W Kupiec, Marwan N Sabbagh, Christopher van Dyck, Ronald G Thomas, Paul S Aisen, Alzheimer's Disease Cooperative Study

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

Trial report in Neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 4 pooled it
12.2field-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

100 citing papers in PubMed, 4 syntheses or guidelines pooled it, 178 citations in OpenAlex.

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40 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

9 authors at 3 institutions in 1 country.

Douglas GalaskoFrom the Department of Neurosciences (D.G., R.G.T., P.S.A.), University of California, San Diego; Pfizer Global Research & Development (J.B., J.Y.M., J.W.K.), Cambridge, MA; Banner Sun Health Research Institute (M.N.S.), Sun City; University of Arizona (M.N.S.), Tucson; and the Department of Psychiatry (C.v.D.), Yale University, New Haven, CT.
Joanne Bell
Jessica Y Mancuso
James W Kupiec
Marwan N Sabbagh
Christopher van Dyck
Ronald G Thomas
Paul S Aisen
Alzheimer's Disease Cooperative Study
University of Arizona · USBanner Sun Health Research Institute · USPfizer (United States) · US

Funding

TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALASKO, DOUGLAS R · 1985 to 2018
$55.4M
NIA NIH HHS AG10483NIA NIH HHS P50 AG005131NIA NIH HHS U19 AG010483
6 · The paper itself

Abstract

objectiveTo examine safety, tolerability, and efficacy of PF-04494700, an inhibitor of the receptor for advanced glycation end products (RAGE), in mild to moderate Alzheimer disease (AD).

methodsDouble-blind, placebo-controlled trial at 40 academic centers (United States). Subjects with AD and Mini-Mental State Examination score 14-26 were randomized to PF-04494700 60 mg/day × 6 days, then 20 mg daily (high dose); 15 mg/day × 6 days, then 5 mg daily (low dose); or placebo, for 18 months. Clinical and laboratory measures were used to evaluate safety and tolerability. The primary efficacy measure was the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog). Secondary measures assessed clinical stage, function, behavior, MRI, and CSF biomarkers.

resultsA total of 399 subjects were randomized. In a prespecified interim analysis, when 50% of subjects had completed the 6-month visit, the high dose was associated with confusion, falls, and greater ADAS-cog decline and was discontinued. A second prespecified analysis compared low-dose and placebo groups for futility and safety approximately 12 months after all subjects were randomized. This analysis met criteria for futility, and treatment was discontinued. There were no safety concerns in the low-dose group. Analyses including post-futility data showed decreased decline on the ADAS-cog in the low-dose group at month 18. Other clinical and biomarker measures showed no differences between low-dose treatment and placebo.

conclusionsPF-04494700 at 20 mg/d was associated with increased adverse events and cognitive decline. At 5 mg/d, PF-04494700 had a good safety profile. A potential benefit for this low dose on the ADAS-cog is not conclusive, because of high dropout and discontinuation rates subsequent to the interim analyses. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with AD high-dose PF-04494700 increased cognitive decline at 6 months and Class IV evidence that low-dose PF-04494700 slowed cognitive decline at 18 months.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntipsychotic AgentsCognition DisordersDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleFemaleFollow-Up StudiesGlycation End Products, AdvancedHumansMaleMiddle AgedOutcome Assessment, Health CareAmyloid beta-PeptidesAntipsychotic AgentsGlycation End Products, Advanced

Identifiers

PMID24696507
PMCPMC4011464
OpenAlexW2105799653

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.