Evidence mapPaperPMID 25012289Full record

Trial reportJournal of the American Heart Association2014

Effects of an antisense oligonucleotide inhibitor of C-reactive protein synthesis on the endotoxin challenge response in healthy human male volunteers.

Robert Noveck, Erik S G Stroes, JoAnn D Flaim, Brenda F Baker, Steve Hughes, Mark J Graham, Rosanne M Crooke, Paul M Ridker

Open access · goldAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 45 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Review
  6. C-reactive protein in diabetic kidney disease: A new therapeutic avenue?Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  7. IL-6 and Cardiovascular Risk: A Narrative Review.Current atherosclerosis reports · 2024
    Review
  8. Review
  9. Role of C-Reactive Protein in Kidney Diseases.Kidney diseases (Basel, Switzerland) · 2023
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Therapeutic Lowering of C-Reactive Protein.Frontiers in immunology · 2020
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Novel biomarkers for cardiovascular risk prediction.Journal of geriatric cardiology : JGC · 2017
    Review
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

8 authors at 4 institutions in 2 countries.

Robert NoveckDuke Clinical Research Institute, Duke University Medical Center, Durham, NC (R.N.).
Erik S G StroesAcademic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (E.G.S.).
JoAnn D FlaimIsis Pharmaceuticals, Inc., Carlsbad, CA (J.A.D.F., B.F.B., S.H., M.J.G., R.M.C.).
Brenda F BakerIsis Pharmaceuticals, Inc., Carlsbad, CA (J.A.D.F., B.F.B., S.H., M.J.G., R.M.C.).
Steve HughesIsis Pharmaceuticals, Inc., Carlsbad, CA (J.A.D.F., B.F.B., S.H., M.J.G., R.M.C.).
Mark J GrahamIsis Pharmaceuticals, Inc., Carlsbad, CA (J.A.D.F., B.F.B., S.H., M.J.G., R.M.C.).
Rosanne M CrookeIsis Pharmaceuticals, Inc., Carlsbad, CA (J.A.D.F., B.F.B., S.H., M.J.G., R.M.C.).
Paul M RidkerCenter for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.R.).
Ionis Pharmaceuticals (United States) · USAcademic Medical Center · NLBrigham and Women's Hospital · USClinical Research Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundC-reactive protein (CRP) binds to damaged cells, activates the classical complement pathway, is elevated in multiple inflammatory conditions, and provides prognostic information on risk of future atherosclerotic events. It is controversial, however, as to whether inhibiting CRP synthesis would have any direct anti-inflammatory effects in humans. METHODS AND

resultsA placebo-controlled study was used to evaluate the effects of ISIS 329993 (ISIS-CRPR x) on the acute-phase response after endotoxin challenge in 30 evaluable subjects. Healthy adult males were randomly allocated to receive 6 injections over a 22-day period of placebo or active therapy with ISIS 329993 at 400- or 600-mg doses. Eligible subjects were subsequently challenged with a bolus of endotoxin (2 ng/kg). Inflammatory and hematological biomarkers were measured before and serially after the challenge. ISIS-CRPR x was well tolerated with no serious adverse events. Median CRP levels increased more than 50-fold from baseline 24 hours after endotoxin challenge in the placebo group. In contrast, the median increase in CRP levels was attenuated by 37% (400 mg) and 69% (600 mg) in subjects pretreated with ISIS-CRPR x (P<0.05 vs. placebo). All other aspects of the acute inflammatory response were similar between treatment groups.

conclusionPretreatment of subjects with ISIS-CRPR x selectively reduced the endotoxin-induced increase in CRP levels in a dose-dependent manner, without affecting other components of the acute-phase response. These data demonstrate the specificity of antisense oligonucleotides and provide an investigative tool to further define the role of CRP in human pathological conditions.

Indexed as

Acute-Phase ReactionAdolescentAdultChemokine CCL2C-Reactive ProteinEndotoxinsE-SelectinFibrin Fibrinogen Degradation ProductsHealthy VolunteersHumansInterleukin-6MaleOligonucleotidesOligonucleotides, AntisensePeptide FragmentsProthrombinCCL2 protein, humanChemokine CCL2C-Reactive ProteinEndotoxinsE-SelectinFibrin Fibrinogen Degradation Productsfibrin fragment DIL6 protein, humanInterleukin-6ISIS 329993OligonucleotidesOligonucleotides, AntisensePeptide FragmentsProthrombinprothrombin fragment 1.2Tumor Necrosis Factor-alphaacute phase responseantisense inhibitorC‐reactive proteinendotoxinhealthy volunteers

Identifiers

PMID25012289
PMCPMC4310401
OpenAlexW2114047027

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.