Evidence map›Paper›PMID 21592048›Full record

Trial reportCurrent Alzheimer research2011

Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies.

C Harrington, S Sawchak, C Chiang, J Davies, C Donovan, A M Saunders, M Irizarry, B Jeter, M Zvartau-Hind, C H van Dyck and 1 more

4 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Current Alzheimer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 98 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 4 pooled it
9.2field-weighted citation impact, top 2% 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.

NCT02409238 phase4terminatedstarted 2015, after this paper: background citation

Insulin Resistance and Mild Cognitive Impairment (MCI) in Older Chinese Adults With Pre-Diabetes and Diabetes: Cognitive Effects of Lifestyle Intervention and Metformin Treatment in a Randomized Controlled Trial

Ran2015Enrolled105Registered outcomes16Posted comparisons0ConditionsDiabetes Mellitus, Type 2, Insulin Resistance, Mild Cognitive ImpairmentArmsIntensive Lifestyle Intervention, Metformin, Standard LIfestyle Recommendation
Open the trial in the graph
NCT00348140 phase3completednot on this map

A 54 Week, Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Acetylcholinesterase Inhibitors on Cognition and Overall Clinical Response in APOE4-stratified Subjects With Mild to Moderate Alzheimer's Disease

TypeinterventionalSponsorGlaxoSmithKlineRan2006 to 2009Enrolled1,468ConditionsAlzheimer's DiseaseArmsRosiglitazone Extended Release 2mg, Rosiglitazone Extended Release 8mg, Placebo
NCT00348309 nacompletednot on this map

A 54-week, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Donepezil on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease.

TypeinterventionalSponsorGlaxoSmithKlineRan2006 to 2009Enrolled1,496ConditionsAlzheimer's DiseaseArmsRosiglitazone Extended Release 2mg, Rosiglitazone Extended Release 8mg, Placebo, Donepezil
NCT00490568 phase3terminatednot on this map

An Open-label Extension to Study AVA102670 and AVA102672, to Assess the Long-term Safety and Efficacy of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy on Cognition in Subjects With Mild to Moderate Alzheimer's Disease.

TypeinterventionalSponsorGlaxoSmithKlineRan2007 to 2009Enrolled1,461ConditionsAlzheimer's DiseaseArmsRosiglitazone XR
3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 4 syntheses or guidelines pooled it, 192 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Trial
  7. Trial
  8. Trial
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review

38 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

11 authors at 1 institution in 1 country.

C HarringtonNeurosciences Medicines Development Center, GlaxoSmithKline, Research Triangle Park, NC, USA. conn.m.harrington@gsk.com
S Sawchak
C Chiang
J Davies
C Donovan
A M Saunders
M Irizarry
B Jeter
M Zvartau-Hind
C H van Dyck
M Gold
Research Triangle Park Foundation · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionTwo phase 3 studies evaluated the efficacy and safety of rosiglitazone (RSG), a type 2 diabetes treatment, in an extended release (RSG XR) form as adjunctive therapy to ongoing acetylcholine esterase inhibitor (AChEI) treatment in AD (REFLECT-2, adjunctive to donepezil; REFLECT-3, to any AChEI). An open-label extension study (REFLECT-4) assessed RSG XR long-term safety.

methodsIn these two double-blind, placebo-controlled studies, subjects with mild-to-moderate probable AD were randomized within 2 apolipoprotein E (APOE) allelic strata (APOE ε4-positive, APOE ε4-negative) to once daily placebo, 2 mg RSG XR, or 8 mg RSG XR for 48 weeks (REFLECT-2, N=1,496; REFLECT-3, N=1,485). Co-primary efficacy endpoints were change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Clinical Dementia Rating scale - Sum of Boxes (CDR-SB) scores at week 48. Three populations were analyzed: APOE4-negative, all subjects except APOE ε4 homozygotes, and the full intent-to-treat population.

resultsNo statistically or clinically relevant differences between treatment groups were observed on the a priori primary endpoints in REFLECT-2 or REFLECT-3. Edema was the most frequent adverse event with RSG in each study (14% and 19%, respectively, at 8 mg RSG XR).

conclusionsNo evidence of statistically or clinically significant efficacy in cognition or global function was detected for 2 mg or 8 mg RSG XR as adjunctive therapy to ongoing AChEIs. There was no evidence of an interaction between treatment and APOE status. Safety and tolerability of RSG XR was consistent with the known profile of rosiglitazone.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseChemotherapy, AdjuvantCholinesterase InhibitorsDonepezilDouble-Blind MethodFemaleHumansHypoglycemic AgentsIndansMaleMiddle AgedNeuropsychological TestsPiperidinesRosiglitazoneCholinesterase InhibitorsDonepezilHypoglycemic AgentsIndansPiperidinesRosiglitazoneThiazolidinediones

Identifiers

PMID21592048
OpenAlexW2146876810

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.