Evidence map›Paper›PMID 28381506›Full record

Trial reportNeurology2017

A phase 3 trial of IV immunoglobulin for Alzheimer disease.

Norman R Relkin, Ronald G Thomas, Robert A Rissman, James B Brewer, Michael S Rafii, Christopher H van Dyck, Clifford R Jack, Mary Sano, David S Knopman, Rema Raman and 5 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00818662 (A Randomized, Double-Blind, Placebo-Controlled, Two Dose Arm, Parallel Study of the Safety and Effectiveness of Immune Globulin Intravenous), which is not on this map. Cited by 75 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 6 pooled it
11.5field-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.

NCT00818662 phase3completednot on this map

A Randomized, Double-Blind, Placebo-Controlled, Two Dose Arm, Parallel Study of the Safety and Effectiveness of Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for the Treatment of Mild-to-Moderate Alzheimer´s Disease

TypeinterventionalSponsorBaxalta now part of ShireRan2008 to 2012Enrolled390ConditionsAlzheimer´s DiseaseArmsImmune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kg, Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kg, Placebo solution: Human Albumin 0.25% - 4 mL/kg, Placebo solution: Human Albumin 0.25% - 2 mL/kg
3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 6 syntheses or guidelines pooled it, 149 citations in OpenAlex.

  1. Pooled it
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  7. Trial
  8. 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
  9. Genetic evidence suggests a protective role of immunoglobulin M in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  10. Review
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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Norman R RelkinFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Ronald G ThomasFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Robert A RissmanFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
James B BrewerFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Michael S RafiiFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Christopher H van DyckFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Clifford R JackFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Mary SanoFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
David S KnopmanFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Rema RamanFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Paul SzaboFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
David M GelmontFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Sandor FritschFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
Paul S AisenFrom Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL. paisen@usc.edu.
Alzheimer's Disease Cooperative Study
University of Southern California · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
VESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHIMMING, CORBETT · 1985 to 2019
$37.9M
PSYCHOSOCIAL COREP30AG008051 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SHAO, YONGZHAO · 1990 to 2019
$36.1M
The VETSA Longitudinal Twin Study of Cognition and Aging (VETSA 4)R01AG050595 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELMAN, JEREMY A, FRANZ, CAROL ELAINE · 2015 to 2024
$28.0M
PREDICTING ALZHEIMERS DISEASE WITH MAGNETIC RESONANCER01AG011378 · NIA · MAYO CLINIC ROCHESTER · PI JACK, CLIFFORD R. · 1993 to 2017
$12.1M
TRAINING IN THE NEUROPLASTICITY OF AGINGT32AG000216 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOO, EDWARD H. · 1992 to 2017
$8.4M
Early detection of Alzheimer's (MCI stage): Analysis of plasma cell-free miRNAR44AG044860 · NIA · DIAMIR, LLC · PI UMANSKY, SAMUIL R · 2015 to 2022
$8.0M
Validating the New Criteria for Preclinical Alzheimer's diseaseR01AG041851 · NIA · MAYO CLINIC ROCHESTER · PI JACK, CLIFFORD R., KNOPMAN, DAVID S · 2012 to 2021
$6.3M
NCATS NIH HHS UL1 TR001863NIA NIH HHS P30 AG008051NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005138NIA NIH HHS R01 AG011378NIA NIH HHS R01 AG034062NIA NIH HHS R01 AG037551NIA NIH HHS R01 AG041851NIA NIH HHS R01 AG043392NIA NIH HHS R01 AG050595NIA NIH HHS R01 AG051848NIA NIH HHS R21 AG047484NIA NIH HHS R21 AG051839NIA NIH HHS R43 AG044860NIA NIH HHS R44 AG044860NIA NIH HHS T32 AG000216NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

objectiveWe tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia.

methodsIn a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants.

resultsNo beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo.

conclusionsParticipants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. CLINICALTRIALSGOV IDENTIFIER: NCT00818662. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4BiomarkersBrainCanadaCognitionDouble-Blind MethodFemaleHumansImmunoglobulins, IntravenousMaleMiddle AgedNootropic AgentsAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Apolipoprotein E4BiomarkersImmunoglobulins, IntravenousNootropic AgentsPeptide Fragments

Identifiers

PMID28381506
PMCPMC5409846
OpenAlexW2604612717

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.